@article {pmid40562221,
year = {2025},
author = {De Marco, M and Chauhan, S and Bocchetta, M and Venneri, A},
title = {Semantic distances of WAIS Similarities word pairs in non-demented adults: An item-level index of semantic memory granularity.},
journal = {Brain research bulletin},
volume = {},
number = {},
pages = {111439},
doi = {10.1016/j.brainresbull.2025.111439},
pmid = {40562221},
issn = {1873-2747},
abstract = {Innovative approaches to test scoring can help neuropsychologists detect subtle semantic memory alterations. We focussed on the Wechsler Adult Intelligence Scale Similarities (SIM) test and calculated an item-level score based on the 'Leacock & Chodorow '(LCH) semantic distance expressed by each SIM item. We hypothesised that LCH would predict 1) performance on standard semantic memory tests; 2) an Alzheimer aetiology; 3) transentorhinal grey-matter integrity. Six hundred sixty-nine non-demented participants completed a neuropsychological battery inclusive of SIM and consolidated tests of semantic memory and executive functioning. Hierarchical linear regressions were designed to test the association between LCH and semantic memory performance after controlling for major confounders. A hierarchical logistic regression was then designed to test the association between LCH and underlying aetiology (Alzheimer/cerebrovascular) in a mild cognitive impairment sub-cohort. Finally, we tested the association between LCH and both whole-brain grey-matter density and transentorhinal thickness using voxel-based-morphometry and region-of-interest models. LCH predicted semantic memory performance but not on a test significantly supported by executive resources. LCH also predicted clinical aetiology and grey-matter density in the transentorhinal cortex and in other regions involved in linguistic-semantic processing. No significant association was found with regional thickness. Post-hoc LCH scoring in 89 people with dementia revealed the presence of a gradient of diagnostic severity, i.e., healthy adults < mild cognitive impairment < dementia. Item-level scores of SIM performance are associated with neurocognitive constituents of semantic memory. LCH is a valuable construct that could help clinicians detect semantic memory decline in ageing adults with suspected neurodegeneration.},
}

@article {pmid40562196,
year = {2025},
author = {Taha, DE and Kabel, AM and Yassin, AI and Abdin, AA},
title = {The potential mitigating effect of febuxostat alone or with donepezil on scopolamine-induced Alzheimer's disease in rats: The role of TXNIP/NLRP3 inflammasome signaling pathway.},
journal = {European journal of pharmacology},
volume = {},
number = {},
pages = {177875},
doi = {10.1016/j.ejphar.2025.177875},
pmid = {40562196},
issn = {1879-0712},
abstract = {BACKGROUND: Alzheimer's disease (AD) is a pervasive neurodegenerative disorder. Despite extensive research, its multifactorial etiology remains complex and not fully understood. The present study was performed to investigate the potential ameliorative effect of febuxostat and donepezil each alone or in combination on scopolamine-induced AD in male Wistar rats via targeting Thioredoxin-interacting protein (TXNIP)/NOD-like receptor protein-3 (NLRP3) inflammasome pathway.

METHODS: In a rat model of scopolamine-induced AD, the changes in the behavioral tests, biochemical parameters, and the histopathological picture in the hippocampal and cerebral tissues were assessed.

RESULTS: Administration of either donepezil or febuxostat to scopolamine-induced AD rats significantly improved the behavioral changes, decremented TXNIP levels with amelioration of the neuroinflammation by decreased NLRP3, and IL-1β levels, restoration of the oxidant/antioxidant balance and inhibition of apoptosis by increasing expression of anti-apoptotic protein Bcl-2 with restoration of ACh levels. Notably, only febuxostat causes normalization of fasting blood glucose levels. These changes were positively reflected on the histopathological picture and scoring in both tissues. These beneficial effects were significantly more evidenced in rats treated with donepezil/febuxostat combination relative to monotherapy by either donepezil or febuxostat. The impact of the tested parameters in the disease outcome was evidenced by their significant correlation and moreover the causality by the significant regression, shedding light particularly for the glycemic state and the neuroinflammatory reactions.

CONCLUSION: These elaborated data signified the neuroprotective effect of febuxostat and indicated that donepezil/febuxostat combination strengthened each other as they act by different mechanisms to counteract AD.},
}

@article {pmid40562015,
year = {2025},
author = {Keng, A and Kapustin, D and Ma, C and Bingham, KS and Fischer, CE and Mah, L and Gallagher, D and Butters, MA and Bowie, CR and Voineskos, AN and Graff-Guerrero, A and Flint, AJ and Herrmann, N and Pollock, BG and Mulsant, BH and Rajji, TK and Kumar, S and , },
title = {Neuropsychiatric Symptoms Present Differently in Individuals with Different High-Risk States of Dementia.},
journal = {Dementia and geriatric cognitive disorders},
volume = {},
number = {},
pages = {1-18},
doi = {10.1159/000547061},
pmid = {40562015},
issn = {1421-9824},
abstract = {BACKGROUND: Neuropsychiatric symptoms (NPS) are common in neurocognitive disorders. However, the differences in presentation of NPS in high-risk states for dementia such as mild neurocognitive disorder (Mild NCD) and remitted major depressive disorder (rMDD) remain unclear.

PURPOSE: To compare the frequency and factor structure of NPS in Mild NCD, rMDD, and Mild NCD with rMDD (Mild NCD-rMDD).

METHODS: We analyzed baseline data from the multicenter Prevention of Alzheimer's Dementia with Cognitive Remediation plus Transcranial Direct Current Stimulation in Mild Cognitive Impairment and Depression trial (NCT0238667). NPS were assessed using the Neuropsychiatric Inventory Questionnaire in those with Mild NCD, rMDD, and Mild NCD-rMDD. We compared the NPS frequency and factor structure across the three groups.

RESULTS: Among 374 participants with a mean (SD) age = 72.0 (6.3) years, the overall frequency of any NPS was highest in Mild NCD-rMDD group (75.9%), as compared to Mild NCD (63.5%) or rMDD (55.7%) groups (p =0.014). Depression/dysphoria was the most common NPS in all three groups. In factor analyses, NPS grouped into four factor structures in all three groups, but the composition of factors in terms of individual symptoms (delusions, motor disturbances, nighttime behaviors, anxiety and apathy) were different across the groups.

CONCLUSIONS: NPS are common in high-risk states for dementia, and the frequency of NPS is higher in Mild NCD-rMDD as compared to only Mild NCD or rMDD. Further, there are key differences in presentation of NPS in Mild NCD, rMDD and Mild NCD-rMDD. Future studies should investigate the relevance of these differences for cognition, function, and disease biomarkers.},
}

@article {pmid40561856,
year = {2025},
author = {Kaise, R and Kitamura, K and Watanabe, Y and Kabasawa, K and Takahashi, A and Saito, T and Kobayashi, R and Oshiki, R and Yamazaki, O and Watanabe, K and Takachi, R and Tsugane, S and Nakamura, K},
title = {Green tea consumption and dementia risk in community-dwelling Japanese people aged 40-74 years: A 12-year cohort study.},
journal = {The journal of nutrition, health & aging},
volume = {29},
number = {8},
pages = {100615},
doi = {10.1016/j.jnha.2025.100615},
pmid = {40561856},
issn = {1760-4788},
abstract = {OBJECTIVE: Green tea, like coffee, has been suggested to protect against dementia, but supporting evidence is lacking. The present study aimed to determine independent associations of green tea consumption with, and interactions of green tea and coffee consumption on, dementia risk in middle-aged and older people.

METHODS: The present study is a 12-year follow-up of the Murakami cohort study on age-related diseases. Participants were 13,660 (men, 6,573 [48.1%]; mean age, 59.0 (SD = 9.3) years) community-dwelling residents aged 40-74 years. The baseline survey was conducted between 2011-2013. A self-administered questionnaire obtained information on predictors, including sex, age, marital status, education, occupation, body size, physical activity, smoking, alcohol, tea and coffee consumption, energy intake, and medical history. Green tea consumption was quantitatively determined with a validated questionnaire. Cases of incident dementia were identified using the long-term care insurance database.

RESULTS: Higher green tea consumption was associated with lower hazard ratios (HRs) for dementia (multivariable P for trend = 0.0178), with the highest quartile having a lower HR (adjusted HR = 0.75) than the lowest quartile. The adjusted HR for dementia by cup-based green tea consumption (1 cup = 150 mL) was 0.952 (95%CI:0.92-0.99), corresponding to a 4.8% reduction per 1 cup increase. High consumption of both green tea and coffee was not associated with low dementia risk (P for interaction = 0.0210).

CONCLUSION: Higher consumption of green tea is independently associated with a lower risk of dementia. Although green tea was found to be beneficial, excessive consumption of both green tea and coffee is not recommended for the prevention of dementia.},
}

@article {pmid40561701,
year = {2025},
author = {Fukazawa, A and Hotta, N and Yeganehjoo, H and Hori, A and Kim, HK and Iwamoto, GA and Smith, SA and Vongpatanasin, W and Mizuno, M},
title = {Blunted pressor response to peripheral sensory afferent nerve stimulation in intracerebroventricular-streptozotocin injected rats.},
journal = {Autonomic neuroscience : basic & clinical},
volume = {260},
number = {},
pages = {103315},
doi = {10.1016/j.autneu.2025.103315},
pmid = {40561701},
issn = {1872-7484},
abstract = {Alzheimer's disease (AD) is the most common neurodegenerative disorder. It is characterized by synaptic loss and the increase of amyloid β (Aβ) in the brain often detrimentally affecting function. Brainstem is the key central integration site for sensory input from working skeletal muscle. Stimulation of skeletal muscle afferent fibers during muscle contraction increases blood pressure. However, whether AD alters or preserves the central processing of peripheral sensory afferent signals remains to be elucidated. Thus, we tested the hypothesis that the magnitude of the pressor response is functionally altered in intracerebroventricular-streptozotocin injected rats (ICV-STZ). Streptozotocin (3 mg/kg) was intracerebroventricularly injected into the lateral ventricle of male Sprague-Dawley rats. In parallel, a separate group of rats were treated with ICV saline as a vehicle control. Spatial learning and memory function were assessed using the Morris Water Maze behavioral test. Results demonstrate that ICV-STZ rats had a significantly longer time to reach a target platform compared to controls (P = 0.0046). ICV-STZ injection also significantly increased brainstem Aβ1-40 (P = 0.0082), but not Aβ1-42 (P = 0.0744). Further, the peak pressor and cardioaccelerator responses to tibial nerve stimulation were significantly attenuated in ICV-STZ rats compared to controls (ΔMAP: P = 0.0003, ΔHR: P = 0.0035). The findings suggest that the cardiovascular responses to electrical stimulation of sensory afferents are blunted in ICV-STZ rats.},
}

@article {pmid40561557,
year = {2025},
author = {Choo, CM and Tan, CH and , },
title = {Effects of regional white matter hyperintensities and β-amyloid on domain-specific cognition and progression to dementia.},
journal = {Brain and cognition},
volume = {188},
number = {},
pages = {106332},
doi = {10.1016/j.bandc.2025.106332},
pmid = {40561557},
issn = {1090-2147},
abstract = {White matter hyperintensities (WMHs) and cerebral β-amyloid (Aβ) have been characterized as clinically significant biomarkers associated with greater cognitive decline and incidence of Alzheimer's Disease (AD) dementia. However, it remains unclear how their regional manifestations co-contribute to domain-specific cognition and dementia onset. We investigated 200 cognitively normal (CN) and 523 individuals with mild cognitive impairment (MCI). We first quantified regional WMHs and Aβ accumulation in the four cerebral lobes. Next, we evaluated the effects of both WMHs and Aβ in each lobe on memory, executive function (EF), language, and visuospatial function. We used Cox proportional hazard models to determine the contributions of both regional WMHs and Aβ to dementia progression. In CN individuals, greater WMHs in parietal and temporal regions were associated with poorer EF beyond Aβ. In MCI individuals, greater Aβ burden in all lobes were associated with poorer memory, EF, and language abilities beyond WMHs. Lastly, both greater occipital WMHs and Aβ predicted progression to dementia. Temporo-parietal WMHs may drive early decline in EF beyond regional Aβ, while occipital WMHs play a critical role in disease progression to AD dementia beyond regional Aβ, highlighting the complex interplay of regional WMHs and Aβ on domain-specific cognitive and clinical function.},
}

@article {pmid40561381,
year = {2025},
author = {Gogniat, MA and Khan, OA and Ratangee, B and Bolton, CJ and Zhang, P and Liu, D and Pechman, KR and Yates, A and Gaynor, LS and Eaton, J and Peterson, A and Gifford, KA and Hohman, TJ and Blennow, K and Zetterberg, H and Jefferson, AL},
title = {Cross-Sectional and Longitudinal Associations of Neighborhood Disadvantage With Fluid Biomarkers of Neuroinflammation and Neurodegeneration.},
journal = {Neurology},
volume = {105},
number = {2},
pages = {e213770},
doi = {10.1212/WNL.0000000000213770},
pmid = {40561381},
issn = {1526-632X},
mesh = {Humans ; Male ; Female ; Cross-Sectional Studies ; Aged ; Biomarkers/cerebrospinal fluid/blood ; Longitudinal Studies ; Chitinase-3-Like Protein 1/cerebrospinal fluid ; tau Proteins/cerebrospinal fluid/blood ; Amyloid beta-Peptides/cerebrospinal fluid/blood ; *Neuroinflammatory Diseases/cerebrospinal fluid/blood/epidemiology ; *Alzheimer Disease/cerebrospinal fluid/blood/epidemiology ; Aged, 80 and over ; *Neighborhood Characteristics ; Peptide Fragments/cerebrospinal fluid ; },
abstract = {BACKGROUND AND OBJECTIVES: Living in a socioeconomically disadvantaged neighborhood has an adverse impact on health outcomes, including increased risk of Alzheimer disease (AD). The biological mechanisms underlying this risk are poorly understood. We sought to examine how neighborhood disadvantage relates to core AD pathology, neurodegeneration, and inflammatory biomarkers in community-dwelling older adults cross-sectionally and over time.

METHODS: Participants included older adults from the Vanderbilt Memory and Aging Project who underwent fasting blood and CSF acquisition serially over a 9-year follow-up period (mean follow-up = 6.4 years [blood] and 4.0 years [CSF]). Area Deprivation Index (ADI), representing neighborhood disadvantage, was quantified at baseline using 17 components (e.g., housing, income, education, and household characteristics), with higher values indicating greater disadvantage. Ordinary least-squares regressions cross-sectionally related ADI to plasma and CSF inflammatory biomarkers adjusting for age, sex, race/ethnicity, education, modified Framingham Stroke Risk Profile score, APOE ε4 status, and cognitive status. Linear mixed-effects regression models related ADI to longitudinal biomarkers with identical covariates plus follow-up time. Outcomes included CSF chitinase-3-like protein 1 (YKL-40), CSF soluble-triggering receptor expressed on myeloid cells 2, CSF amyloid-β42 (Aβ42), CSF Aβ40/Aβ42 ratio, CSF tau, CSF phosphorylated tau (ptau), plasma high-sensitivity C-reactive protein (CRP), and plasma and CSF neurofilament light chain.

RESULTS: Participants (n = 334; 73 ± 8 years old, 59% male, 86% White, non-Hispanic) on average were from relatively less disadvantaged neighborhoods (ADI national decile = 33 ± 25, range = 1-98). Greater neighborhood disadvantage at study entry was cross-sectionally associated with elevated CSF YKL-40 (β = 0.7, p = 0.003) and tau (β = 1.8, p = 0.04) after excluding outliers. Greater neighborhood disadvantage at study entry related to faster longitudinal increases in plasma CRP (β = 0.005, p = 0.03).

DISCUSSION: Greater neighborhood disadvantage was associated with elevated inflammatory and AD CSF biomarkers cross-sectionally and longitudinal increases in a nonspecific inflammatory blood biomarker. Findings suggest that neighborhood disadvantage confers risk of systemic inflammation and AD pathology, providing a possible sociobiological mechanism underlying health disparities in aging adults; however, results were limited by use of ADI at study entry.},
}

Humans
Male
Female
Cross-Sectional Studies
Aged
Biomarkers/cerebrospinal fluid/blood
Longitudinal Studies
Chitinase-3-Like Protein 1/cerebrospinal fluid
tau Proteins/cerebrospinal fluid/blood
Amyloid beta-Peptides/cerebrospinal fluid/blood
*Neuroinflammatory Diseases/cerebrospinal fluid/blood/epidemiology
*Alzheimer Disease/cerebrospinal fluid/blood/epidemiology
Aged, 80 and over
*Neighborhood Characteristics
Peptide Fragments/cerebrospinal fluid

@article {pmid40561143,
year = {2025},
author = {Bsoul, R and Simonsen, AH and Frederiksen, KS and Svenstrup, K and Bech, S and Salvesen, L and Hejl, AM and Rossi, M and Parchi, P and Lund, EL and Areškevičiūtė, A},
title = {Seeding amplification assay with Universal Control Fluid: Standardized detection of α-synucleinopathies.},
journal = {PloS one},
volume = {20},
number = {6},
pages = {e0326568},
doi = {10.1371/journal.pone.0326568},
pmid = {40561143},
issn = {1932-6203},
mesh = {Humans ; *alpha-Synuclein/cerebrospinal fluid/genetics ; *Synucleinopathies/diagnosis/cerebrospinal fluid ; Parkinson Disease/cerebrospinal fluid/diagnosis ; Sensitivity and Specificity ; Lewy Body Disease/cerebrospinal fluid/diagnosis ; Male ; Aged ; Female ; Multiple System Atrophy/cerebrospinal fluid/diagnosis ; },
abstract = {Seeding amplification assays, specifically the Real-Time Quaking-Induced Conversion method (RT-QuIC), have shown great diagnostic potential for α-synucleinopathies. Numerous research groups have demonstrated the method's high sensitivity and specificity using cerebrospinal fluid (CSF) samples and various RT-QuIC workflows. However, establishing a uniform and stably performing RT-QuIC protocol remains challenging. To address this, we established an RT-QuIC protocol with a Universal Control Fluid (UCF), which is simple to adopt, performs stably, and allows uniform preparation of both sample and control reactions. Firstly, we adapted and established a published 48-hour RT-QuIC protocol, including the in-house production of recombinant α-synuclein (rec α-syn), and evaluated its sensitivity and specificity through a blinded screening of an 81 CSF sample cohort consisting of Parkinson's disease (PD), dementia with Lewy bodies (DLB), Alzheimer's disease, motor neuron disease, multiple system atrophy, unidentified neurodegenerative diseases, and healthy controls. Additionally, we tested all CSF samples in three volumes to determine which volume provides the best diagnostic accuracy. The established RT-QuIC performs nearly equally well with 7 µL and 15 µL added CSF, resulting in 94% and 94.5% diagnostic accuracy, respectively. Secondly, we developed a UCF solution and tested its performance with the established RT-QuIC protocol. Results indicate that UCF, used in defined volume and concentration, standardizes the preparation of both sample and control reactions without compromising the assay's diagnostic accuracy and provides a stabilizing environment for the reactions, ensuring higher reproducibility. The established RT-QuIC protocol for pathologic α-synuclein detection in PD and DLB CSF samples is highly sensitive (92-96%) and specific (93-96%). Therefore, it is important that its adoption in clinical laboratories is uncomplicated and uniform. RT-QuIC with UCF simplifies, standardizes, and stabilizes the assay's performance and, thus, could be recommended as a standard protocol for accurate detection of α-synucleinopathies.},
}

Humans
*alpha-Synuclein/cerebrospinal fluid/genetics
*Synucleinopathies/diagnosis/cerebrospinal fluid
Parkinson Disease/cerebrospinal fluid/diagnosis
Sensitivity and Specificity
Lewy Body Disease/cerebrospinal fluid/diagnosis
Male
Aged
Female
Multiple System Atrophy/cerebrospinal fluid/diagnosis

@article {pmid40561107,
year = {2025},
author = {Jock, J and Beidelman, ET and Phillips, M and Kobayashi, LC and Chen, X and Tollman, S and Kabudula, CW and Bassil, DT and Wagner, R and Berkman, L and Rosenberg, M},
title = {Effects of pension eligibility expansion on men's memory decline and dementia probability: Findings from the HAALSI cohort in rural South Africa, 2014-2021.},
journal = {PloS one},
volume = {20},
number = {6},
pages = {e0326321},
doi = {10.1371/journal.pone.0326321},
pmid = {40561107},
issn = {1932-6203},
mesh = {Humans ; Male ; South Africa/epidemiology ; *Pensions/statistics & numerical data ; Rural Population ; *Dementia/epidemiology ; Aged ; Middle Aged ; *Memory Disorders/epidemiology ; Cohort Studies ; Cognitive Dysfunction/epidemiology ; Alzheimer Disease/epidemiology ; },
abstract = {Alzheimer's disease and related dementias (ADRD) are a growing global health concern, with burdens projected to expand rapidly in the coming decades. Since cognitive decline typically precedes ADRD, it is crucial to identify interventions that may help slow cognitive decline and reduce ADRD risk. We used a quasi-experimental design, exploiting exogenous expansions of South Africa's Older Persons Grant for men, to estimate its impact on memory decline and ADRD risk in the rural Mpumalanga province of South Africa. We found that expanded pension eligibility was associated with slower memory decline for men who were eligible to receive the pension 5 years earlier [β = 0.027 SD, 95% CI = 0.023, 0.031], as well as for men who were eligible to receive the pension 1-4 years earlier [β = 0.009 SD, 95% CI = 0.004, 0.013]. We also found a 5.2 percentage point lower probability of dementia for men who were eligible for pension 5 years earlier [95% CI = -0.062, -0.032] and a 4.8 percentage point lower probability of dementia for men who became eligible to receive pension 1-4 years earlier [95% CI = -0.062, -0.032]. These findings demonstrate that beyond the policy intent of cash transfers to strengthen individual and household livelihoods, an important further benefit lies in promoting healthy cognitive aging in low- and middle- income countries.},
}

Humans
Male
South Africa/epidemiology
*Pensions/statistics & numerical data
Rural Population
*Dementia/epidemiology
Aged
Middle Aged
*Memory Disorders/epidemiology
Cohort Studies
Cognitive Dysfunction/epidemiology
Alzheimer Disease/epidemiology

@article {pmid40560959,
year = {2025},
author = {Shah, M and Pervaiz, S and Ahmad, I and Ansari, SH and Junior, VFP and Ahmed, S and Khan, MU and Fawy, KF and Nishan, U and Dib, H and Abdelfattah, MAO},
title = {Computer-aided discovery of dual-target compounds for Alzheimer's from ayurvedic medicinal plants.},
journal = {PloS one},
volume = {20},
number = {6},
pages = {e0325441},
doi = {10.1371/journal.pone.0325441},
pmid = {40560959},
issn = {1932-6203},
mesh = {*Alzheimer Disease/drug therapy ; Humans ; Amyloid Precursor Protein Secretases/antagonists & inhibitors/metabolism/chemistry ; Molecular Dynamics Simulation ; *Plants, Medicinal/chemistry ; *Medicine, Ayurvedic ; Acetylcholinesterase/metabolism/chemistry ; *Cholinesterase Inhibitors/chemistry/pharmacology ; Aspartic Acid Endopeptidases/antagonists & inhibitors/metabolism/chemistry ; *Drug Discovery/methods ; Molecular Docking Simulation ; Principal Component Analysis ; Hydrogen Bonding ; Triterpenes/chemistry ; },
abstract = {Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive decline, driven by the accumulation of amyloid-beta plaques and neurofibrillary tangles. It involves the dysfunction of key enzymes such as Acetylcholinesterase (AChE) and β-secretase (BACE1), making them critical targets for therapeutic intervention. In this study we investigated an in-house library of 820 secondary metabolites obtained from Ayurvedic plants against AChE and BACE1 with the aim to discover novel leads for AD. Virtual screening resulted in 15 ligands, mostly belonging to the ursane-type or dammarene-type triterpene saponins of Centella asiatica, reestablishing the potency of this plant in drug discovery against AD. The binding affinities were further verified by molecular dynamics (MD) simulation trajectories, including root mean square fluctuations (RMSF), root mean square deviation (RMSD), hydrogen bonding analysis, Coulomb interaction calculation, Lennard-Jones interactions, and the total interaction energy. Moreover, extensive Principal Component Analysis (PCA) and Gibbs free energy landscape were performed. Our results demonstrated three compounds, namely (S)-eriodictyol 7-O-(6-β-O-trans-p-coumaroyl)-β-d-glucopyranoside, sitoindoside-X and 1,5-di-o-caffeoyl quinic acid as more effective in treating AD due to their comparable drug-like properties. Drug-likeness, structural chemistry, pharmacophore, and ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) analysis support their potential for future drug development. To establish the effectiveness of these lead compounds against AD, additional experimental testing should be performed.},
}

*Alzheimer Disease/drug therapy
Humans
Amyloid Precursor Protein Secretases/antagonists & inhibitors/metabolism/chemistry
Molecular Dynamics Simulation
*Plants, Medicinal/chemistry
*Medicine, Ayurvedic
Acetylcholinesterase/metabolism/chemistry
*Cholinesterase Inhibitors/chemistry/pharmacology
Aspartic Acid Endopeptidases/antagonists & inhibitors/metabolism/chemistry
*Drug Discovery/methods
Molecular Docking Simulation
Principal Component Analysis
Hydrogen Bonding
Triterpenes/chemistry

@article {pmid40560947,
year = {2025},
author = {Krick, KE and Wilcock, DM},
title = {A Change of Mind: Targeting Amyloid-β with Better Safety Profile.},
journal = {Annual review of pharmacology and toxicology},
volume = {},
number = {},
pages = {},
doi = {10.1146/annurev-pharmtox-062124-113434},
pmid = {40560947},
issn = {1545-4304},
abstract = {Alzheimer's disease (AD) is a complex neurodegenerative disease that leads to cognitive decline and dementia. Over the past two decades, many scientists have contributed to the discovery of therapeutics that target amyloid-beta (Aβ) to slow the progression of AD. These discoveries have led to the development of the first disease-modifying therapeutics in AD, though these come with the risk of side effects known as amyloid-related imaging abnormalities (ARIA). There are currently many exciting studies and trials working to mitigate ARIA risk that range from modifying antibodies to potential combination therapeutics. This review addresses some of the ongoing research areas for improving safety in Aβ targeting as well as clinical considerations for current patient treatment.},
}

@article {pmid40560886,
year = {2025},
author = {Wang, J and Yu, ZW and Liu, Q and Wu, JX and Zhang, YD and Wan, HJ and Bi, M and Xiao, NA and Zheng, KM and Jiang, B},
title = {Novel insights from comprehensive analysis: The role of cuproptosis and peripheral immune infiltration in Alzheimer's disease.},
journal = {PloS one},
volume = {20},
number = {6},
pages = {e0325799},
doi = {10.1371/journal.pone.0325799},
pmid = {40560886},
issn = {1932-6203},
mesh = {*Alzheimer Disease/immunology/genetics/pathology ; Humans ; Molecular Docking Simulation ; Gene Expression Profiling ; },
abstract = {BACKGROUND: Cuproptosis is increasingly recognized as an essential factor in the pathological process of Alzheimer's disease (AD). However, the specific role of cuproptosis-related genes in AD remains poorly understood.

METHODS: Our first step was to obtain gene expression data from the GEO database and identify differentially expressed cuproptosis-associated genes (DECAGs) in AD. GO, KEGG, and GSEA analyses were then conducted on these genes. Subsequently, we attempted to classify AD patients by unsupervised clustering. Then, four machine-learning models were used to screen hub-genes from the DECAGs. We also explored the immune features of these genes and predicted target drugs. Molecular docking analysis was then performed on the predicted drugs and their corresponding hub-gene related proteins. Candidate markers were then validated by single-cell analysis and intracellular communication was investigated in a GEO scRNA-seq dataset. Lastly, we examined the expression levels of the hub-genes in peripheral blood cells using real-time quantitative PCR.

RESULTS: 19 DECAGs were found in AD and the key biological processes and molecular functions associated with AD were further determined. Two subtypes of peripheral blood cells showed significant alternations in AD: Cluster1 and Cluster2. Five hub-genes including FDX1, GLS, PDK1, MAP2K1, and SOD1 were then screened out from the machine-learning study. All of the five hub-genes were significantly correlated with various immunocytes. We discovered compounds targeting hub-gene related proteins and forecasted multiple strong hydrogen bonding interactions between the picked predicted drugs and the target proteins by molecular docking analysis. Subsequently, in the single-cell analysis of AD peripheral blood, all hub-genes except SOD1 were found to be up-regulated in B cells, NK cells, and CD4+ T cells, possibly acting on the MIF pathway. Finally, we discovered that the levels of PDK1 expression in AD patients were remarkably upregulated, while FDX1 and GLS were significantly decreased using qPCR.

CONCLUSION: This study examined changes in intercellular communication between immune cells in the peripheral blood and identified five novel feature genes associated with cuproptosis in AD patients. These results facilitated a deeper understanding of the molecular mechanisms of AD and suggested novel therapeutic targets.},
}

*Alzheimer Disease/immunology/genetics/pathology
Humans
Molecular Docking Simulation
Gene Expression Profiling

@article {pmid40560822,
year = {2025},
author = {Turner, CG and Good, ME and DuPont, JJ},
title = {New clues on sex-specific cerebrovascular aging.},
journal = {American journal of physiology. Heart and circulatory physiology},
volume = {},
number = {},
pages = {},
doi = {10.1152/ajpheart.00421.2025},
pmid = {40560822},
issn = {1522-1539},
support = {F32HL176055//HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R21AG075796//HHS | NIH | National Institute on Aging (NIA)/ ; R01HL160834//HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; },
}

@article {pmid40560635,
year = {2025},
author = {Gottlieb, M and Golovashkina, N and Stein, BD and Casey, P and Walker, G and Thompson, D},
title = {Factors associated with unplanned admissions among patients with chronic conditions.},
journal = {The American journal of managed care},
volume = {31},
number = {Spec. No. 6},
pages = {SP312-SP321},
doi = {10.37765/ajmc.2025.89755},
pmid = {40560635},
issn = {1936-2692},
mesh = {Humans ; Female ; Male ; Retrospective Studies ; United States ; Middle Aged ; Aged ; *Multiple Chronic Conditions/epidemiology ; Chronic Disease/epidemiology ; Medicare/statistics & numerical data ; Adult ; Risk Factors ; *Hospitalization/statistics & numerical data ; Medicaid/statistics & numerical data ; Aged, 80 and over ; },
abstract = {OBJECTIVES: Value-based care models, such as the Medicare Shared Savings Program, have placed increasing emphasis on unplanned admissions among patients with multiple chronic conditions (UAMCCs) as a quality metric. However, there are limited data on which factors are associated with the highest risk of UAMCCs. This study sought to determine which factors were associated with increased risk of UAMCCs.

STUDY DESIGN: Retrospective study conducted among all adult patients with 2 or more chronic conditions defined by CMS presenting to 2 hospitals within a major Midwest health care system from November 1, 2022, to October 31, 2023.

METHODS: Demographics, chronic conditions, primary care physician (PCP) visit utilization, and annual wellness visit (AWV) utilization were analyzed using multivariable logistic regression to identify associations with UAMCCs.

RESULTS: Among 18,448 patients (55.8% women) included in the study, 3842 (20.8%) had at least 1 UAMCC. Patients with UAMCCs were more likely to have Medicare or Medicaid insurance; be widowed; speak Spanish; have a higher Charlson Comorbidity Index score; and have Alzheimer disease, atrial fibrillation, heart failure, chronic kidney disease, depression, chronic obstructive pulmonary disease, and/or stroke. When examining PCP visit measures, AWVs and having 1 or more PCP visits were associated with fewer UAMCCs.

CONCLUSIONS: Higher Charlson Comorbidity Index scores, several health conditions, and Spanish language were associated with increased UAMCCs. AWVs and having 1 or more PCP visits were associated with fewer UAMCCs.},
}

Humans
Female
Male
Retrospective Studies
United States
Middle Aged
Aged
*Multiple Chronic Conditions/epidemiology
Chronic Disease/epidemiology
Medicare/statistics & numerical data
Adult
Risk Factors
*Hospitalization/statistics & numerical data
Medicaid/statistics & numerical data
Aged, 80 and over

@article {pmid40560607,
year = {2025},
author = {Pignataro, P and Dicarlo, M and Zecca, C and Urso, D and Dell'Abate, MT and Vilella, D and Borlizzi, F and Zerlotin, R and Oranger, A and Colaianni, G and Colucci, S and Grano, M and Logroscino, G},
title = {Correlation Between Irisin and Cognitive Functions in Alzheimer Dementia.},
journal = {Annals of clinical and translational neurology},
volume = {},
number = {},
pages = {},
doi = {10.1002/acn3.70117},
pmid = {40560607},
issn = {2328-9503},
support = {//Regione Puglia and CNR for Tecnopolo per la Medicina di Precisione. D.G.R. n. 2117 of 21.11.2018 (CUP: B84I18000540002)-C.I.R.E.M.I.C. (Research Center of Excellence for Neurodegenerative Diseases and Brain Aging)-University of Bari "Aldo Moro"/ ; //Next Generation EU, in the context of the National Recovery and Resilience Plan, Investment PE8 - Project Age-It: "Ageing Well in an Ageing Society". This resource was co-financed by the Next Generation EU [DM 1557 11.10.2022] (CUP:H33C22000680006)/ ; },
abstract = {OBJECTIVE: The myokine irisin, a recent positive mediator of exercise in the brain, shows neuroprotective functions against Alzheimer's disease (AD). The association between irisin and cognition has never been explored in a biologically defined cohort of patients. Thus, in the present study, we investigated the association of irisin with multidomain cognition in patients showing dementia-related symptomatology.

METHODS: Cerebrospinal fluid (CSF) and serum irisin levels were evaluated using enzyme-linked immunoassays in a cohort of subjects with a confirmed biomarker evidence of AD, including AD (n = 82), mild cognitive impairment (MCI, n = 44), and subjective memory complaint (SMC, n = 20) patients. The results of this analysis were correlated with global cognitive efficiency assessed by Mini-Mental State Examination, and multidomain cognition evaluated by a battery of psychometric tests.

RESULTS: Decreased CSF and serum irisin levels were observed in AD and MCI patients compared to SMC. A significant correlation has been found between irisin in the CSF and global cognitive efficiency, as well as with specific cognitive domains such as memory, executive functions, attention, visuospatial abilities, and language. For serum irisin, the correlation analysis evidenced similar results to those observed for the CSF.

INTERPRETATION: Our results highlight the key involvement of irisin in multidomain cognition, indicating its potential role as a cognitive biomarker of AD progression.},
}

@article {pmid40560489,
year = {2025},
author = {Abdel-Aziem, A and Fouad, SA},
title = {Recent advances in pyrazolo[3,4-b]pyridine chemistry: synthesis techniques and biological activity.},
journal = {Molecular diversity},
volume = {},
number = {},
pages = {},
pmid = {40560489},
issn = {1573-501X},
abstract = {In recent years, attention has been drawn to pyrazolo[3,4-b] pyridine and its derivatives due to their substantial pharmacological activities such as antidepressant, anticancer, antiviral, antifungal, antioxidant, anticoagulant, anti-Alzheimer, and antimicrobial. Besides their medicinal uses, they act as herbicides, fungicides, and are also used as agrochemicals, inhibitors for a wide range of kinases, and fibroblast growth factor receptors. Additionally, pyrazolo[3,4-b] pyridines are used in developing organic materials for different applications such as chemosensors and corrosion inhibitors for mild steel. This review aims to provide an in-depth overview of the latest advancements regarding synthetic routes, reactions, and biological importance of pyrazolo [3,4-b] pyridine during 2019-2025 which will be a useful resource for interested researchers engaged in this area. The synthetic methodologies focus on metal-catalyst, nanocatalyst, microwave-assisted synthesis, multicomponent reactions, and other green chemistry approaches. Emphasizing the significance of these scaffolds in drug discovery and medicinal chemistry, new developments and future directions in the design of innovative pyrazolo[3,4-b]pyridine-based therapies are also covered.},
}

@article {pmid40560468,
year = {2025},
author = {Sumra, V and Hadian, M and Dilliott, AA and Farhan, SMK and Frank, AR and Lang, AE and Roberts, AC and Troyer, A and Arnott, SR and Marras, C and Tang-Wai, DF and Finger, E and Rogaeva, E and Orange, JB and Ramirez, J and Zinman, L and Binns, M and Borrie, M and Freedman, M and Ozzoude, M and Bartha, R and Swartz, RH and Munoz, D and Masellis, M and Black, SE and Dixon, RA and Dowlatshahi, D and Grimes, D and Hassan, A and Hegele, RA and Kumar, S and Pasternak, S and Pollock, B and Rajji, T and Sahlas, D and Saposnik, G and Tartaglia, MC and , },
title = {Regional free-water diffusion is more strongly related to neuroinflammation than neurodegeneration.},
journal = {Journal of neurology},
volume = {272},
number = {7},
pages = {478},
pmid = {40560468},
issn = {1432-1459},
mesh = {Humans ; Male ; Aged ; Female ; *Neurodegenerative Diseases/diagnostic imaging/metabolism ; *Diffusion Magnetic Resonance Imaging/methods ; *Neuroinflammatory Diseases/diagnostic imaging/metabolism ; Middle Aged ; Neurofilament Proteins/blood ; Glial Fibrillary Acidic Protein/blood ; Biomarkers/blood ; Aged, 80 and over ; Cognitive Dysfunction/diagnostic imaging ; },
abstract = {INTRODUCTION: Recent research has suggested that neuroinflammation may be important in the pathogenesis of neurodegenerative diseases. Free-water diffusion (FWD) has been proposed as a non-invasive neuroimaging-based biomarker for neuroinflammation.

METHODS: Free-water maps were generated using diffusion MRI data in 367 patients from the Ontario Neurodegenerative Disease Research Initiative (108 Alzheimer's Disease/Mild Cognitive Impairment, 42 Frontotemporal Dementia, 37 Amyotrophic Lateral Sclerosis, 123 Parkinson's Disease, and 58 vascular disease-related Cognitive Impairment). The ability of FWD to predict neuroinflammation and neurodegeneration from biofluids was estimated using plasma glial fibrillary-associated protein (GFAP) and neurofilament light chain (NfL), respectively.

RESULTS: Recursive Feature Elimination (RFE) performed the strongest out of all feature selection algorithms used and revealed regional specificity for areas that are the most important features for predicting GFAP over NfL concentration. Deep learning models using selected features and demographic information revealed better prediction of GFAP over NfL.

DISCUSSION: Based on feature selection and deep learning methods, FWD was found to be more strongly related to GFAP concentration (measure of astrogliosis) over NfL (measure of neuro-axonal damage), across neurodegenerative disease groups, in terms of predictive performance. Non-invasive markers of neurodegeneration such as MRI structural imaging that can reveal neurodegeneration already exist, while non-invasive markers of neuroinflammation are not available. Our results support the use of FWD as a non-invasive neuroimaging-based biomarker for neuroinflammation.},
}

Humans
Male
Aged
Female
*Neurodegenerative Diseases/diagnostic imaging/metabolism
*Diffusion Magnetic Resonance Imaging/methods
*Neuroinflammatory Diseases/diagnostic imaging/metabolism
Middle Aged
Neurofilament Proteins/blood
Glial Fibrillary Acidic Protein/blood
Biomarkers/blood
Aged, 80 and over
Cognitive Dysfunction/diagnostic imaging

@article {pmid40560244,
year = {2025},
author = {Alum, EU and Akwari, AA and Okoroh, PN and Aniokete, UC and Abba, JN and Uti, DE},
title = {Phytochemicals as modulators of ferroptosis: a novel therapeutic avenue in cancer and neurodegeneration.},
journal = {Molecular biology reports},
volume = {52},
number = {1},
pages = {636},
pmid = {40560244},
issn = {1573-4978},
mesh = {*Ferroptosis/drug effects ; Humans ; *Phytochemicals/pharmacology/therapeutic use ; *Neurodegenerative Diseases/drug therapy/metabolism ; *Neoplasms/drug therapy/metabolism ; Oxidative Stress/drug effects ; Animals ; Lipid Peroxidation/drug effects ; Antioxidants/pharmacology ; Iron/metabolism ; Catechin/analogs & derivatives ; },
abstract = {Ferroptosis, a controlled cell death mechanism characterised by iron-dependent lipid peroxidation, has become a significant factor in the pathophysiology of cancer and neurodegenerative disorders. Its dual role as a tumor suppressor and mediator of neuronal damage highlights its significance as a therapeutic target. Phytochemicals, natural bioactive molecules in plants, have attracted interest for their ability to modulate ferroptosis through diverse mechanisms, including regulation of oxidative stress, iron metabolism, and antioxidant defense systems. This review examines the complex relationship between ferroptosis and disease mechanisms, emphasizing its relevance in treatment-resistant cancers and neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. Information was taken from reputable databases such as PubMed, Scopus, and Web of Science. We thoroughly analyzed the current evidence on phytochemicals-including polyphenols like curcumin and epigallocatechin gallate, flavonoids like quercetin and luteolin, and alkaloids like berberine-as modulators of ferroptotic pathways. Despite their promising therapeutic potential, challenges such as limited bioavailability, pharmacokinetics, and clinical validation remain significant hurdles. Future research focusing on advanced delivery systems, synergistic approaches, and personalized medicine strategies could unlock the full potential of phytochemicals in ferroptosis-targeted therapies. This review underscores phytochemicals as a novel and versatile avenue in addressing the unmet therapeutic needs in cancer and neurodegenerative diseases.},
}

*Ferroptosis/drug effects
Humans
*Phytochemicals/pharmacology/therapeutic use
*Neurodegenerative Diseases/drug therapy/metabolism
*Neoplasms/drug therapy/metabolism
Oxidative Stress/drug effects
Animals
Lipid Peroxidation/drug effects
Antioxidants/pharmacology
Iron/metabolism
Catechin/analogs & derivatives

@article {pmid40560182,
year = {2025},
author = {Katabathula, S and Gurney, M and Perry, G and Davis, PB and Xu, R},
title = {Identifying patients with mild cognitive impairment at high risk of transitioning to Alzheimer's disease using routinely collected data.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877251351622},
doi = {10.1177/13872877251351622},
pmid = {40560182},
issn = {1875-8908},
abstract = {BackgroundMild cognitive impairment (MCI) is a heterogeneous condition with variable progression to Alzheimer's disease (AD). Identifying MCI individuals at high risk for progression typically requires cerebrospinal fluid (CSF) biomarkers, magnetic resonance imaging (MRI), which are costly and invasive.ObjectiveThis study aimed to develop a cost-effective approach using routinely collected clinical data to identify a subgroup of MCI individuals at high risk for AD progression.MethodsAnalyses were conducted using the UK Biobank dataset, focusing on 1019 participants identified as having MCI, using the ICD-10 code F06.7 (mild neurocognitive disorder due to known physiological condition) in the absence of a dedicated diagnostic code for MCI. Participants (mean age = 71.7 years; 44% women) were characterized using routinely recorded demographic, comorbidity, and lifestyle data. A mixed-data clustering model was applied to classify individuals into subgroups. Clinical relevance of each cluster was evaluated using Kaplan-Meier survival analysis of MCI-to-AD progression over an average follow-up of 4.5 years.ResultsThree subtypes were identified with distinct progression risks: high-risk (HR), medium-risk (MR), and low-risk (LR). The HR subtype had significantly higher prevalence of hypertension (98%), cardiovascular disease (89%), diabetes (48%), and high cholesterol (67%) than MR and LR (p < 0.05). The HR group was younger on average but had greater comorbidity burden and higher likelihood of AD progression.ConclusionsThis study demonstrates the feasibility of using routinely collected data to identify high-risk MCI individuals. This approach offers a practical preliminary screening tool to prioritize individuals for targeted interventions and further specialized assessments.},
}

@article {pmid40560181,
year = {2025},
author = {Salvioni Chiabotti, P and Nasuti, M and Rouaud, O and Allali, G},
title = {Posterior cortical atrophy in the age of anti-amyloid treatments: An 11-year retrospective study of eligible patients from the Leenaards Memory Center.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877251342266},
doi = {10.1177/13872877251342266},
pmid = {40560181},
issn = {1875-8908},
abstract = {At the era of the anti-amyloid treatments (AAT), it is striking to note posterior cortical atrophy (PCA) cases, the most predictive phenotype of Alzheimer's disease neuropathology, have not been explicitly included or excluded from clinical trials. In a retrospective analysis of the Leenaards Memory Center registry, we identified 41 PCA cases and, applying the recent appropriate use recommendations for lecanemab, estimate high (20%) eligibility rate, that doubles in pure PCA phenotypes with biomarker work-up available (40%). This high proportion of PCA patients eligible for AAT should prompt a timely exploration to assess inclusion/exclusion criteria for these novel therapies.},
}

@article {pmid40560007,
year = {2025},
author = {Nemoto, K and Mathis, BJ and Iwasaka, A and Nakayama, K and Kaneta, T and Arai, T},
title = {The Image Clarity Paradox: Higher CZT SPECT Contrast Does Not Always Translate to Diagnostic Accuracy for Alzheimer's Disease.},
journal = {Tomography (Ann Arbor, Mich.)},
volume = {11},
number = {6},
pages = {},
doi = {10.3390/tomography11060061},
pmid = {40560007},
issn = {2379-139X},
mesh = {Humans ; *Alzheimer Disease/diagnostic imaging ; *Tomography, Emission-Computed, Single-Photon/methods/instrumentation ; Female ; Male ; Zinc ; Cadmium ; Aged ; Tellurium ; Middle Aged ; Sensitivity and Specificity ; Gray Matter/diagnostic imaging ; Brain/diagnostic imaging ; Aged, 80 and over ; },
abstract = {Background: Recent advances in single-photon emission computed tomography (SPECT) technology, particularly cadmium-zinc-telluride (CZT) detectors, have improved spatial resolution and contrast in cerebral blood flow imaging. This study aimed to investigate whether these improvements translate to enhanced diagnostic accuracy for Alzheimer's disease (AD). Methods: We compared conventional SPECT (eCAM) with CZT SPECT in 29 patients (mean age 60.9 ± 17.6 years, 69% female) with suspected neurodegenerative diseases. Results: Gray matter/white matter contrast was significantly higher in CZT SPECT compared to eCAM (1.615 ± 0.096 vs. 1.458 ± 0.068, p < 0.001). However, diagnostic accuracy for AD did not improve with CZT SPECT. For the participating psychiatrist, sensitivity decreased from 0.750 (eCAM) to 0.625 (CZT), while for the radiologist, specificity dropped from 0.571 (eCAM) to 0.429 (CZT). Overall accuracy slightly decreased for both readers. Conclusions: These findings suggest that while CZT SPECT offers superior image quality, it may not immediately translate to improved diagnostic accuracy for AD. The study highlights the importance of specialized training for clinicians in interpreting higher-resolution CZT SPECT images to fully leverage their potential in neurodegenerative disease diagnosis. Future research should focus on developing standardized training protocols and larger, multi-center studies to validate these findings.},
}

Humans
*Alzheimer Disease/diagnostic imaging
*Tomography, Emission-Computed, Single-Photon/methods/instrumentation
Female
Male
Zinc
Cadmium
Aged
Tellurium
Middle Aged
Sensitivity and Specificity
Gray Matter/diagnostic imaging
Brain/diagnostic imaging
Aged, 80 and over

@article {pmid40559632,
year = {2025},
author = {Zhang, R and Ren, Y and Ren, T and Yu, Y and Li, B and Zhou, X},
title = {Marine-Derived Antioxidants: A Comprehensive Review of Their Therapeutic Potential in Oxidative Stress-Associated Diseases.},
journal = {Marine drugs},
volume = {23},
number = {6},
pages = {},
doi = {10.3390/md23060223},
pmid = {40559632},
issn = {1660-3397},
mesh = {*Oxidative Stress/drug effects ; *Antioxidants/pharmacology/therapeutic use/chemistry/isolation & purification ; Humans ; *Aquatic Organisms/chemistry ; Animals ; Neurodegenerative Diseases/drug therapy ; Cardiovascular Diseases/drug therapy ; *Biological Products/pharmacology ; Reactive Oxygen Species/metabolism ; },
abstract = {Oxidative stress is a critical factor contributing to the pathogenesis of numerous diseases, including cardiovascular disorders, diabetes, and neurodegenerative conditions. In recent years, marine-derived antioxidants have emerged as promising therapeutic agents due to their unique biological activities and diverse sources. This comprehensive review explores the therapeutic potential of various marine antioxidants in mitigating oxidative stress-associated diseases. Marine organisms are rich in bioactive compounds, such as polysaccharides, polyphenols, carotenoids, peptides, and vitamins, which exhibit potent antioxidant and free radical scavenging abilities. These compounds have been shown to effectively inhibit oxidative reactions, repair oxidative damage, and enhance the body's antioxidant defense mechanisms. For instance, marine polysaccharides and their derivatives can scavenge reactive oxygen species (ROS), protect neurons from oxidative damage, and alleviate inflammation in neurodegenerative diseases like Alzheimer's and Parkinson's diseases. Similarly, marine unsaturated fatty acids, such as omega-3 polyunsaturated fatty acids (PUFAs), have been found to reduce cardiovascular risks by lowering serum triglyceride levels and improving vascular endothelial function. Additionally, marine-derived superoxide dismutase (SOD) plays a crucial role in neutralizing ROS, thereby offering protection against oxidative stress in various diseases. Despite these promising findings, challenges remain in the field, including the need for improved extraction and purification technologies, more comprehensive activity evaluation systems, and further research into the safety and bioavailability of these compounds. This review provides a detailed overview of the current research status, highlighting the types, structural characteristics, antioxidant activities, and mechanisms of action of marine antioxidants. It also identifies key areas for future research and development, aiming to harness the full potential of marine-derived antioxidants in the prevention and treatment of oxidative stress-related diseases.},
}

*Oxidative Stress/drug effects
*Antioxidants/pharmacology/therapeutic use/chemistry/isolation & purification
Humans
*Aquatic Organisms/chemistry
Animals
Neurodegenerative Diseases/drug therapy
Cardiovascular Diseases/drug therapy
*Biological Products/pharmacology
Reactive Oxygen Species/metabolism

@article {pmid40559623,
year = {2025},
author = {Gisa, V and Islam, MR and Lbik, D and Hofmann, RM and Pena, T and Krüger, DM and Burkhardt, S and Schütz, AL and Sananbenesi, F and Toischer, K and Fischer, A},
title = {Role of Compensatory miRNA Networks in Cognitive Recovery from Heart Failure.},
journal = {Non-coding RNA},
volume = {11},
number = {3},
pages = {},
doi = {10.3390/ncrna11030045},
pmid = {40559623},
issn = {2311-553X},
support = {priority program 1738, SFB1286 and GRK2824, Excellence Strategy - EXC 2067/1 390729940//German Research Foundation/ ; EPI-3E//The EU Joint Programme- Neurodegenerative Diseases (JPND)/ ; miRassay (16LW0055)//German Federal Ministry of Science and Education/ ; DZHK Innovation Cluster Brain and Heart Interfaces//DZHK/ ; Heisenberg Stipend//German Resarch Foundation/ ; },
abstract = {Background: Heart failure (HF) is associated with an increased risk of cognitive impairment and hippocampal dysfunction, yet the underlying molecular mechanisms remain poorly understood. This study aims to investigate the role of microRNA (miRNA) networks in hippocampus-dependent memory recovery in a mouse model of HF. Methods: CaMKIIδC transgenic (TG) mice, a model for HF, were used to assess hippocampal function at 3 and 6 months of age. Memory performance was evaluated using hippocampus-dependent behavioral tasks. Small RNA sequencing was performed to analyze hippocampal miRNA expression profiles across both time points. Bioinformatic analyses identified miRNAs that potentially regulate genes previously implicated in HF-induced cognitive impairment. Results: We have previously shown that at 3 months of age, CaMKIIδC TG mice exhibited significant memory deficits associated with dysregulated hippocampal gene expression. In this study, we showed that these impairments, memory impairment and hippocampal gene expression, were no longer detectable at 6 months, despite persistent cardiac dysfunction. However, small RNA sequencing revealed a dynamic shift in hippocampal miRNA expression, identifying 27 miRNAs as "compensatory miRs" that targeted 73% of the transcripts dysregulated at 3 months but reinstated by 6 months. Notably, miR-181a-5p emerged as a central regulatory hub, with its downregulation coinciding with restored memory function. Conclusions: These findings suggest that miRNA networks contribute to the restoration of hippocampal function in HF despite continued cardiac pathology and provide an important compensatory mechanism towards memory impairment. A better understanding of these compensatory miRNA mechanisms may provide novel therapeutic targets for managing HF-related cognitive dysfunction.},
}

@article {pmid40559413,
year = {2025},
author = {Malcangi, G and Marinelli, G and Inchingolo, AD and Trilli, I and Ferrante, L and Casamassima, L and Nardelli, P and Inchingolo, F and Palermo, A and Inchingolo, AM and Dipalma, G},
title = {Salivaomics: New Frontiers in Studying the Relationship Between Periodontal Disease and Alzheimer's Disease.},
journal = {Metabolites},
volume = {15},
number = {6},
pages = {},
doi = {10.3390/metabo15060389},
pmid = {40559413},
issn = {2218-1989},
abstract = {BACKGROUND: This study explores the link between oral biofluids, microbial dysbiosis, and Alzheimer's disease (AD), highlighting saliva and gingival crevicular fluid (GCF) as non-invasive diagnostic sources. AD onset and progression appear to be influenced not only by genetic and environmental factors but also by changes in the oral microbiome and related inflammatory and metabolic alterations. As global populations age, the incidence of AD is projected to rise significantly. Emerging evidence implicates the oral microbiome and salivary metabolites in neurodegenerative pathways, suggesting that oral health may mirror or influence brain pathology.

MATERIALS AND METHODS: A systematic review of recent multi-omics studies was performed, focusing on salivary and GCF analysis in patients with AD, those with mild cognitive impairment (MCI), and cognitively healthy individuals. Databases searched included PubMed, Web of Science, and Scopus, following PRISMA guidelines.

RESULTS: Across the 11 included studies, significant alterations were reported in both the salivary microbiome and metabolome in AD patients. Notable microbial shifts involved increased abundance of Veillonella parvula and Porphyromonas gingivalis, while key metabolites such as L-tyrosine, galactinol, and mannitol were consistently dysregulated. These biomarkers correlated with cognitive performance and systemic inflammation.

CONCLUSIONS: Oral biofluids represent promising, accessible sources of biomarkers for early AD detection. Multi-omics integration reveals the oral-brain axis as a potential target for diagnosis, monitoring, and therapeutic strategies.},
}

@article {pmid40559330,
year = {2025},
author = {Twiss, E and McPherson, C and Weaver, DF},
title = {Global Diseases Deserve Global Solutions: Alzheimer's Disease.},
journal = {Neurology international},
volume = {17},
number = {6},
pages = {},
doi = {10.3390/neurolint17060092},
pmid = {40559330},
issn = {2035-8385},
abstract = {Alzheimer's Disease (AD) is a global issue, with increasing incidence and prevalence as the world's population ages and life expectancy increases. Projections indicate that by 2050, over 150 million individuals worldwide will be personally living with AD, an impending crisis made worse by the absence of cure therapies. Moreover, the risk factor relationship of dementia with rising global temperatures and air pollution further necessitates the urgency of a coordinated international response. With an extensive economic and emotional burden, AD is no longer just a disease; it is a worldwide societal crisis. This review presents five calls to action to address the AD global health emergency. First, AD research must be approached as an internationally performed activity, involving standardized data sharing, collaborative innovation, and improved access to pharmaceutical studies in low- and middle-income countries (LMICs), alongside increased diversity, inclusion, and equity in research. Second, there must be a commitment to develop universally accessible, affordable, and non-invasive diagnostic tools for AD. Third, advancements in AD therapeutics should prioritize the development of affordable agents, allowing for widespread geographic distribution. Fourth, we identify focus areas for global dementia risk reduction: sleep, head injury prevention, exercise, learning, and diet (SHIELD risk reduction strategy). Fifth, improving care for individuals with AD requires eliminating stigma through educational programs for both the public and caregivers. The escalating AD crisis demands an unprecedented global coalition in research, diagnostics, therapeutics, prevention, and education to avoid a future where the disease becomes the defining crisis of our era.},
}

@article {pmid40559329,
year = {2025},
author = {Vo, T and Ibrahim, AK and Zhuang, H},
title = {A Multimodal Multi-Stage Deep Learning Model for the Diagnosis of Alzheimer's Disease Using EEG Measurements.},
journal = {Neurology international},
volume = {17},
number = {6},
pages = {},
doi = {10.3390/neurolint17060091},
pmid = {40559329},
issn = {2035-8385},
abstract = {Background/Objectives: Alzheimer's disease (AD) is a progressively debilitating neurodegenerative disorder characterized by the accumulation of abnormal proteins, such as amyloid-beta plaques and tau tangles, leading to disruptions in memory storage and neuronal degeneration. Despite its portability, non-invasiveness, and cost-effectiveness, electroencephalography (EEG) as a diagnostic tool for AD faces challenges due to its susceptibility to noise and the complexity involved in the analysis. Methods: This study introduces a novel methodology employing three distinct stages for data-driven AD diagnosis: signal pre-processing, frame-level classification, and subject-level classification. At the frame level, convolutional neural networks (CNNs) are employed to extract features from spectrograms, scalograms, and Hilbert spectra. These features undergo fusion and are then fed into another CNN for feature selection and subsequent frame-level classification. After each frame for a subject is classified, a procedure is devised to determine if the subject has AD or not. Results: The proposed model demonstrates commendable performance, achieving over 80% accuracy, 82.5% sensitivity, and 81.3% specificity in distinguishing AD patients from healthy individuals at the subject level. Conclusions: This performance enables early and accurate diagnosis with significant clinical implications, offering substantial benefits over the existing methods through reduced misdiagnosis rates and improved patient outcomes, potentially revolutionizing AD screening and diagnostic practices. However, the model's efficacy diminishes when presented with data from frontotemporal dementia (FTD) patients, emphasizing the need for further model refinement to address the intricate nuances associated with the simultaneous detection of various neurodegenerative disorders alongside AD.},
}

@article {pmid40559320,
year = {2025},
author = {Gharaibeh, S and Alsabbah, A and Alloubani, A and Gharaibeh, A},
title = {Reciprocal Interactions Between Periodontal Disease and Alzheimer's Disease: Implications for Mutual Triggering, Exacerbation, and Treatment Interventions-A Comprehensive Review of the Literature.},
journal = {Neurology international},
volume = {17},
number = {6},
pages = {},
doi = {10.3390/neurolint17060081},
pmid = {40559320},
issn = {2035-8385},
abstract = {Periodontal health is connected to many systemic diseases, such as cardiovascular, diabetes mellitus, and neurodegenerative diseases. The oral-brain axis has gained increasing interest in the pathogenesis of diseases. Emerging studies have highlighted the potential role of periodontal disease in the development and progression of Alzheimer's disease. However, Alzheimer's disease also affects periodontal disease and oral health. In this review, we address the correlation between the two diseases and the mechanisms by which one contributes to the other. Exploring the correlation between Alzheimer's disease and periodontal disease will assist in better understanding the pathophysiology of diseases and pave the way for the development of therapeutic and preventive strategies.},
}

@article {pmid40559280,
year = {2025},
author = {Milisavljević, K and Milanović, Ž and Matić, J and Antonijević, M and Simić, V and Milošević, M and Kosanić, M and Kaluđerović, GN},
title = {(Alkyl-ω-ol)triphenyltin(IV)-Loaded Mesoporous Silica as Biocompatible Potential Neuroprotectors: Evaluation of Inhibitory Activity Against Enzymes Associated with the Pathophysiology of Alzheimer's Disease.},
journal = {Nanomaterials (Basel, Switzerland)},
volume = {15},
number = {12},
pages = {},
doi = {10.3390/nano15120914},
pmid = {40559280},
issn = {2079-4991},
abstract = {Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by synaptic dysfunction and neuronal loss due to the accumulation of amyloid-β peptides and tau proteins. In the pursuit of novel neuroprotective strategies, organotin(IV) compounds have garnered attention due to their unique chemical and biological properties. This study evaluates the inhibitory potential of two triphenyltin(IV) derivatives-(3-propan-1-ol)triphenyltin(IV) (Ph3SnL1) and (4-butan-1-ol)triphenyltin(IV) (Ph3SnL2)-in both free form and immobilized into mesoporous silica SBA-15~Cl, targeting acetylcholinesterase (AChE), a key enzyme involved in AD pathophysiology. The SBA-15~Cl|Ph3SnL2 nanostructures exhibited the most potent inhibitory activity against AChE (IC50 = 0.58 μM), significantly outperforming the standard drug galantamine. Molecular docking, molecular dynamics simulations, and MM/GBSA and MM/PBSA analyses confirmed the stability and selectivity of interactions with AChE, primarily driven by hydrophobic interactions. Compound transport was also simulated using a multi-scale 3D mouse brain model to evaluate brain tissue distribution and blood-brain barrier permeability. The results highlight the strong potential of SBA-15-loaded organotin(IV) compounds as biocompatible neuroprotective agents for novel treatments of neurodegenerative diseases.},
}

@article {pmid40559217,
year = {2025},
author = {Wojtecki, L},
title = {Commentary: Treating Diseases from Alzheimer's to Parkinson's Using Transcranial Pulse Stimulation: Mechanistic Insights, Recent Evidence, and Ethical Considerations.},
journal = {NeuroSci},
volume = {6},
number = {2},
pages = {},
doi = {10.3390/neurosci6020056},
pmid = {40559217},
issn = {2673-4087},
abstract = {Transcranial pulse stimulation (TPS) is a non-invasive neuromodulation method that uses, high-intensity acoustic shockwaves to deliver focused mechanical stimulation to neural tissue with minimal thermal effects. The mechanism of action includes but is not limited to promotion of blood flow and angiogenesis through mechanotransduction. Clinical data to date are limited and preliminary. In Alzheimer's disease (AD), TPS has demonstrated cognitive and mood improvements in pilot studies and secondary endpoint analysis in first randomized trials. The enhancement of gamma-band oscillations and network connectivity has been reported. Clinical observations in Parkinson's disease (PD) suggest TPS as a hypothesis-generating approach to address non-motor symptoms-such as depression, cognitive decline, and the freezing of gait-through theoretical modulation of basal ganglia-cortical circuits. TPS is CE-marked in Europe for AD and shows a favorable safety profile; however, ethical considerations arise from the limited evidence base, potential impairment of patient autonomy and judgment in dementia, and the risk of withholding established treatments. TPS should only be offered under structured scientific protocols or within patient registries to ensure rigorous oversight. Ensuring that consent processes account for cognitive capacity, and that TPS is applied as adjunct rather than replacement therapy, is paramount. Future research must include large-scale randomized controlled trials (RCTs), standardize stimulation protocols, deepen mechanistic insight, and embed robust ethical frameworks.},
}

@article {pmid40559212,
year = {2025},
author = {Lee, AW and Hirani, R and Ogulnick, J and Tiwari, RK and Etienne, M},
title = {Emerging Therapies for Neurological Disorders: A Clinical Review of MANAGED (Music, Art, Nature-Based, Animal-Assisted, Game, Essential Oil, Dance) Care.},
journal = {NeuroSci},
volume = {6},
number = {2},
pages = {},
doi = {10.3390/neurosci6020051},
pmid = {40559212},
issn = {2673-4087},
abstract = {In the face of the limitations in pharmacological and surgical interventions for neurological conditions such as Parkinson's and Alzheimer's disease, patients are increasingly turning to non-pharmacological and alternative therapies to manage their symptoms and improve their quality of life. This shift underscores the urgent need for accessible, effective, and affordable treatments. This literature review examines a range of alternative and personalized therapies, including game therapy, animal-assisted therapy, dance therapy, art therapy, music therapy, aroma therapy, and shinrin-yoku therapy. These modalities have demonstrated promising results in mitigating symptoms and enhancing well-being among individuals grappling with neurological disorders. Moreover, these therapies offer a holistic approach that complements traditional medical interventions, underscoring the importance of integrating diverse treatment modalities. Despite their historical roots in non-clinical settings, their potential in modern clinical practice remains untapped. The findings suggest the necessity for further research, particularly large cohort studies, to validate the efficacy of these personalized therapies and advocate for their widespread adoption. In an era marked by escalating healthcare costs, the exploration of alternative therapies presents a compelling avenue for enhancing patient care while simultaneously addressing economic challenges within the healthcare system.},
}

@article {pmid40559211,
year = {2025},
author = {Agostini, M and Traldi, P and Hamdan, M},
title = {Isoforms of Phosphorylated Tau as Potential Biomarkers for Alzheimer's Disease: The Contribution of Mass Spectrometry-Based Proteomics.},
journal = {NeuroSci},
volume = {6},
number = {2},
pages = {},
doi = {10.3390/neurosci6020050},
pmid = {40559211},
issn = {2673-4087},
abstract = {Alzheimer's disease (AD) is a progressive neurodegenerative disorder, heterogeneous at the molecular level and characterized by diverse and complex pathological features. Such features are known to accumulate silently in the brain over years or even decades before the onset of detectable symptoms. Despite long years of intense research activities, the disease remains orphaned of either disease-modifying therapies or a specific blood test capable of predicting the disease in the pre-symptomatic stages. This disappointing outcome of such efforts can be attributed to a number of factors. One of these factors is the failure of earlier research to capture the heterogeneity of the disease. Such failure has the direct consequence of poor patient stratification, which in turn impacts negatively on the development of specific and effective therapy. The second factor is the absence of detailed and accurate information on proteins and associated post-translational modifications, which may influence the initiation and progress of the disease. Recent studies have demonstrated that the quantification of various isoforms of phosphorylated tau protein in plasma and other biofluids can be considered as potential biomarkers for the early detection of Alzheimer's disease. Mass spectrometry-based proteomics and immunoassay-based multiplex proteomics are the two technologies in current use for probing the human proteome, both in tissues and biofluids. In the present review, we discuss the contribution of MS-based proteomics to efforts aimed at the identification and eventual characterization of the heterogeneity of the disease, and the key role of the same technique in the analysis of protein post-translational modifications associated with the disease is also discussed.},
}

@article {pmid40559207,
year = {2025},
author = {Ahmad, SO and Stiles, D and Brown, K and Dillon, L and Shroba, E},
title = {Meta-Analysis of Exercise Effects on Cognition in Persons with Parkinson's Disease.},
journal = {NeuroSci},
volume = {6},
number = {2},
pages = {},
doi = {10.3390/neurosci6020046},
pmid = {40559207},
issn = {2673-4087},
abstract = {BACKGROUND: Parkinson's disease (PD) is a debilitating neurodegenerative disorder affecting millions of people worldwide. PD results in motor and cognitive dysfunction. While there is no proven cure for PD, it is widely agreed that aerobic exercises and occupations can help slow the progression of the disease and keep some motor-related symptoms from developing. The most effective forms of exercise to slow the progression of motor symptoms in Parkinson's disease have also been studied.

RESEARCH QUESTION: This research article aims to compare the differences in outcomes of exercise on cognitive outcomes in Parkinson's Disease, as evaluated by meta-analysis.

METHODS: Key terms were Parkinson's Disease and exercise terms. These search terms were then entered to electronic databases-Ovid MEDLINE, SCOPUS, and CINAHL-from March 2018 to May 2023. An ancestral bibliography was also performed.

RESULTS: Two reviewers screened the title and abstract records (n = 528) found in the initial search. Our review identified 18 studies which met inclusion criteria for meta-analysis. The meta-analysis found an effect of exercise on cognition of patients with PD (d = -0.03) which was not significant (CI95% of -0.13 < µ < 0.08; p > 0.05, as the CI includes zero). Additionally, the homogeneity analysis was not significant (Q (17) = 2.83; p > 0.05).},
}

@article {pmid40559130,
year = {2025},
author = {Chaple-Gil, AM and Santiesteban-Velázquez, M and Urbizo Vélez, JJ},
title = {Association Between Oral Microbiota Dysbiosis and the Risk of Dementia: A Systematic Review.},
journal = {Dentistry journal},
volume = {13},
number = {6},
pages = {},
doi = {10.3390/dj13060227},
pmid = {40559130},
issn = {2304-6767},
abstract = {Background/Objectives: Growing evidence suggests that oral microbiota dysbiosis may contribute to the development of systemic conditions, including neurodegenerative diseases. This dysregulation promotes immunoinflammatory responses that are increasingly associated with dementia. This systematic review aimed to evaluate the association between oral microbiota dysbiosis and the risk of dementia in older adults. Methods: Eligible studies evaluated oral microbial composition using validated methods such as genetic sequencing, bacterial culture, or metagenomic analysis. Following PRISMA guidelines and a PICO framework, the review included cohort, case-control, and cross-sectional studies. Searches were conducted across PubMed, Scopus, Web of Science, Embase, and Cochrane Library. Two independent reviewers screened and selected studies, resolving disagreements through a third evaluator. Results: This systematic review revealed that Tannerella forsythia, Fusobacterium nucleatum, Porphyromonas, Prevotella, Leptotrichia, Fusobacteriota, Peptostreptococcaceae, and Candida spp. were consistently associated with Alzheimer's disease and mild cognitive impairment, indicating their potential role in neurodegeneration. In contrast, Streptococcus gordonii, Gemella haemolysans, Rothia, Neisseria, and Haemophilus were reduced in cognitively impaired individuals, suggesting a link with healthy cognition. Studies also showed decreased microbial diversity in Alzheimer's disease and the possible modifying effect of the APOE4 allele. Oral health interventions improved microbial composition and slowed cognitive decline, supporting the diagnostic and therapeutic potential of oral microbiota modulation. Conclusions: The findings suggest that oral microbiota dysbiosis may not only result from cognitive decline but also contribute to its pathogenesis. Future studies with larger and more diverse cohorts are recommended to validate these associations.},
}

@article {pmid40559126,
year = {2025},
author = {Li, Z and Zhang, Y and Su, R and Yang, J and Chen, F and Chen, L and Yao, C and Li, S and Cui, P and Meng, X and Huang, G},
title = {Notoginsenoside R1, a Novel Natural PPARγ Agonist, Attenuates Cognitive Deficits in a Mouse Model of Diabetic Alzheimer's Disease Through Enhancing GLUT4-Dependent Neuronal Glucose Uptake.},
journal = {Phytotherapy research : PTR},
volume = {},
number = {},
pages = {},
doi = {10.1002/ptr.70006},
pmid = {40559126},
issn = {1099-1573},
support = {82474108//National Natural Science Foundation of China/ ; 82371423//National Natural Science Foundation of China/ ; 2023A1515220241//Basic and Applied Basic Research Foundation of Guangdong Province/ ; 2023A1515030035//Natural Science Foundation of Guangdong Province/ ; 2022A1515012323//Natural Science Foundation of Guangdong Province/ ; 2021A151510836//Natural Science Foundation of Guangdong Province/ ; //Shenzhen Science and Technology Program/ ; JCYJ20220530151006013//Basic research projects of Shenzhen Science and Technology Program/ ; JCYJ20180507184656626//Basic research projects of Shenzhen Science and Technology Program/ ; ZDSYS20140509173142601//Shenzhen Key Laboratory of Neurosurgery/ ; RCBS20210609104629074//Shenzhen Development and Reform Commissions Stroke Screening and Prevention Public Service Platform improving program/ ; //Guangdong Innovation Platform of Translational Research for Cerebrovascular Diseases/ ; },
abstract = {Our previous studies demonstrated the potential of notoginsenoside R1 (NGR1), a primary bioactive compound from Panax notoginseng, in alleviating diabetic encephalopathy in db/db mice and mitigating amyloid-β (Aβ)-induced neuronal damage. This study aimed to investigate the positive effects of NGR1 against cognitive deficits in a diabetic Alzheimer's disease (AD) mouse model (APP/PS1xdb/db mice). APP/PS1xdb/db mice were intragastrically administrated with NGR1 (40 mg/kg/day) or co-administrated with NGR1 and a selective PPARγ inhibitor GW9662 for 16 weeks. We identified NGR1 as a novel PPARγ agonist through molecular docking, surface plasmon resonance, and dual-luciferase reporter assay. NGR1 treatment significantly promoted the membrane translocation of GLUT4 and enhanced 2-deoxyglucose uptake in primary mouse hippocampal neurons. Furthermore, NGR1 treatment notably mitigated cognitive deficits in APP/PS1xdb/db mice. This treatment correlated with reduced blood glucose levels, lowered blood HbA1c, and decreased serum insulin levels, coupled with enhanced glucose tolerance and insulin sensitivity. Additionally, NGR1 treatment ameliorated Aβ burden, suppressed microglia-induced neuroinflammation, and notably increased cerebral glucose uptake, as demonstrated by [18]F-FDG PET scans. NGR1 treatment could upregulate PPARγ and GLUT4 expression and increase phosphorylation of Akt at Ser473 while decreasing phosphorylation of IRS-1 at Ser616 in the hippocampus of APP/PS1xdb/db mice. Crucially, the protective effects of NGR1 were abolished by co-administration with GW9662. NGR1 demonstrated efficacy in enhancing neuronal glucose uptake through the activation of the PPARγ/Akt/GLUT4 signaling pathways in APP/PS1xdb/db mice, positioning it as a promising candidate for diabetic AD treatment.},
}

@article {pmid40558866,
year = {2025},
author = {Botnaru, AA and Lupu, A and Morariu, PC and Jităreanu, A and Nedelcu, AH and Morariu, BA and Anton, E and Di Gioia, ML and Lupu, VV and Dragostin, OM and Vieriu, M and Morariu, ID},
title = {Neurotoxic Effects of Pesticides: Implications for Neurodegenerative and Neurobehavioral Disorders.},
journal = {Journal of xenobiotics},
volume = {15},
number = {3},
pages = {},
doi = {10.3390/jox15030083},
pmid = {40558866},
issn = {2039-4713},
abstract = {Pesticides play an essential role in modern agriculture, yet increasing evidence links their widespread use to neurotoxic effects that contribute to both neurodegenerative and neurodevelopmental disorders. In recent years, new classes of pesticides such as neonicotinoids and pyrethroids have garnered attention due to their potential to disrupt neurodevelopment, even at low exposure levels. Furthermore, emerging evidence underscores the involvement of the gut-brain axis, neuroinflammation, and epigenetic modulation in pesticide-induced neuropathology. This review aims to synthesize these latest advancements while highlighting underexplored mechanisms, thereby offering a comprehensive and current perspective on pesticide-related neurotoxicity. Data from the Rapid Alert System for Food and Feed (RASFF) indicate that several food products include residues of pesticides recognized for their neurotoxic properties. Although environmental exposure levels are lower than those in occupational contexts, the magnitude and persistence of food-based exposure demand thorough evaluation. This review integrates evidence coming from epidemiological, in vivo and in vitro investigations, emphasizing the correlations between pesticide exposure and conditions such as Alzheimer's disease, Parkinson's disease, and cognitive deficits in children. Neurodevelopmental toxicity is especially alarming since symptoms may manifest subtly and with a delayed onset after early-life exposure, indicating the significant neurotoxic potential of pesticide residues and emphasizing the need for their careful evaluation in food safety assessments. Improved regulatory procedures and public health efforts are essential to reducing long-term brain damage.},
}

@article {pmid40558561,
year = {2025},
author = {Jarne-Ferrer, J and Pallàs, M and Griñán-Ferré, C and Bellver-Sanchis, A},
title = {Investigating the Synergistic Neuroprotective Effects of Plant-Derived Antioxidants and the Psychedelic N,N-Dimethyltryptamine in Alzheimer's Disease Therapy.},
journal = {Cells},
volume = {14},
number = {12},
pages = {},
doi = {10.3390/cells14120934},
pmid = {40558561},
issn = {2073-4409},
mesh = {*Alzheimer Disease/drug therapy/pathology ; Animals ; *Antioxidants/pharmacology/therapeutic use ; *Neuroprotective Agents/pharmacology/therapeutic use ; Caenorhabditis elegans/drug effects ; Oxidative Stress/drug effects ; Drug Synergism ; Amyloid beta-Peptides/metabolism ; Humans ; Disease Models, Animal ; Animals, Genetically Modified ; },
abstract = {Alzheimer's disease (AD) is a chronic and complex neurodegenerative disorder characterized by progressive cognitive decline, memory loss, and irreversible impairment of brain functions. The etiology of AD is multifactorial, involving a complex interplay of genetic, environmental, and physiological factors, including the aggregation of amyloid-β (Aβ) and oxidative stress (OS). The role of OS in AD pathogenesis is of particular significance, given that an imbalance between oxidants and antioxidants promotes cellular damage, exacerbates Aβ deposition, and leads to cognitive deterioration. Despite extensive research, current therapeutic strategies have largely failed, likely due to the use of single-target drugs unable to halt the multifactorial progression of the disease. In this study, we investigated the synergistic therapeutic effect of plant-derived bioactive compounds Withanone, Apigenin, Bacoside A, Baicalin, and Thymoquinone in combination with N,N-Dimethyltryptamine (NN-DMT), a psychedelic molecule. We used a transgenic Caenorhabditis elegans model to assess the behavioral and molecular outcomes following compound exposure. Motility assays, thioflavin S staining, and survival assays under oxidative stress were employed to evaluate the treatment efficacy. The results of the behavioral and molecular analyses indicated that the combination therapy exhibited a higher efficacy than the monotherapies, leading to a significant reduction in age-related motility defects in the AD model. Furthermore, the combination treatment substantially reduced Aβ plaque burden, enhanced survival following OS insult, and demonstrated a synergistic effect in mitigating AD-related hallmarks. Taken together, these findings support the potential of combining NN-DMT with specific bioactive compounds as a promising multi-target therapeutic approach for AD.},
}

*Alzheimer Disease/drug therapy/pathology
Animals
*Antioxidants/pharmacology/therapeutic use
*Neuroprotective Agents/pharmacology/therapeutic use
Caenorhabditis elegans/drug effects
Oxidative Stress/drug effects
Drug Synergism
Amyloid beta-Peptides/metabolism
Humans
Disease Models, Animal
Animals, Genetically Modified

@article {pmid40558538,
year = {2025},
author = {Hein, ZM and Vishnumukkala, T and Karikalan, B and Alkatiri, A and Hussan, F and Jagadeesan, S and Kamaruzzaman, MA and Che Ramli, MD and Che Mohd Nassir, CMN and Gopalakrishna, PK},
title = {Autophagy and Alzheimer's Disease: Mechanisms and Impact Beyond the Brain.},
journal = {Cells},
volume = {14},
number = {12},
pages = {},
doi = {10.3390/cells14120911},
pmid = {40558538},
issn = {2073-4409},
mesh = {*Alzheimer Disease/pathology/metabolism ; Humans ; *Autophagy ; *Brain/pathology/metabolism ; Animals ; Amyloid beta-Peptides/metabolism ; Mitophagy ; },
abstract = {Alzheimer's disease (AD) is a progressive neurodegenerative disorder marked by neuronal loss, cognitive decline, and pathological hallmarks such as amyloid-beta (Aβ) plaques and tau neurofibrillary tangles. Recent evidence highlights autophagy as a pivotal mechanism in cellular homeostasis, mediating the clearance of misfolded proteins and damaged organelles. However, impaired autophagy contributes significantly to AD pathogenesis by disrupting proteostasis, exacerbating neuroinflammation, and promoting synaptic dysfunction. This review aims to scrutinize the intricate relationship between autophagy dysfunction and AD progression, explaining key pathways including macroautophagy, chaperone-mediated autophagy (CMA), and selective autophagy processes such as mitophagy and aggrephagy. This further extends the discussion beyond the central nervous system, evaluating the role of hepatic autophagy in Aβ clearance and systemic metabolic regulation. An understanding of autophagy's involvement in AD pathology via various mechanisms could give rise to a novel therapeutic strategy targeting autophagic modulation to mitigate disease progression in the future.},
}

*Alzheimer Disease/pathology/metabolism
Humans
*Autophagy
*Brain/pathology/metabolism
Animals
Amyloid beta-Peptides/metabolism
Mitophagy

@article {pmid40558534,
year = {2025},
author = {Guo, X and Xiang, J and Ye, K and Zhang, Z},
title = {Development of Positron Emission Tomography Radiotracers for Imaging α-Synuclein Aggregates.},
journal = {Cells},
volume = {14},
number = {12},
pages = {},
doi = {10.3390/cells14120907},
pmid = {40558534},
issn = {2073-4409},
support = {No. 82271447//National Natural Science Foundation of China/ ; },
mesh = {Humans ; *alpha-Synuclein/metabolism ; *Positron-Emission Tomography/methods ; Animals ; *Protein Aggregates ; Synucleinopathies/diagnostic imaging/metabolism ; *Radiopharmaceuticals/chemistry ; },
abstract = {Neurodegenerative diseases (NDDs) that are characterized by the accumulation of alpha-synuclein (α-syn) aggregates in both neurons and the non-neuronal cells of the brain are called synucleinopathies. The most common synucleinopathies includes Parkinson's disease (PD), Parkinson's disease dementia (PDD), multiple system atrophy (MSA), and dementia with Lewy bodies (DLB). Significant progress has been made in the development of positron emission tomography (PET) radiotracers for synucleinopathies, yielding several α-syn tracers that have entered clinical studies. However, selective α-syn imaging still faces inherent challenges. This review provides a comprehensive overview of the progress in α-syn PET radiotracers from three angles: Alzheimer's disease (AD)-derived scaffolds, representative compound scaffolds and analogs, and the identification of α-syn tracers through high-throughput screening (HTS). We discuss the characteristics, advantages, and limitations of the tracers for preclinical and clinical application. Finally, future directions in the development of radioligands for proteinopathies are discussed. There is no clinical available PET radiotracer for imaging α-syn aggregates, but these advances have laid a key foundation for non-invasive α-syn imaging and early diagnosis of synucleinopathies.},
}

Humans
*alpha-Synuclein/metabolism
*Positron-Emission Tomography/methods
Animals
*Protein Aggregates
Synucleinopathies/diagnostic imaging/metabolism
*Radiopharmaceuticals/chemistry

@article {pmid40558500,
year = {2025},
author = {Mai, HA and Thomas, CM and Nge, GG and Elefant, F},
title = {Modulating Cognition-Linked Histone Acetyltransferases (HATs) as a Therapeutic Strategy for Neurodegenerative Diseases: Recent Advances and Future Trends.},
journal = {Cells},
volume = {14},
number = {12},
pages = {},
doi = {10.3390/cells14120873},
pmid = {40558500},
issn = {2073-4409},
support = {2RF1NS095799//National Institutes of Health NINDS/ ; 2RF1NS095799/NS/NINDS NIH HHS/United States ; },
mesh = {Humans ; *Neurodegenerative Diseases/therapy/enzymology/drug therapy ; *Histone Acetyltransferases/metabolism ; *Cognition/physiology ; Animals ; Protein Processing, Post-Translational ; Histones/metabolism ; Epigenesis, Genetic ; Acetylation ; Aging ; },
abstract = {Recent investigations into the neuroepigenome of the brain are providing unparalleled understanding into the impact of post-translational modifications (PTMs) of histones in regulating dynamic gene expression patterns required for adult brain cognitive function and plasticity. Histone acetylation is one of the most well-characterized PTMs shown to be required for neuronal function and cognition. Histone acetylation initiates neural circuitry plasticity via chromatin control, enabling neurons to respond to external environmental stimuli and adapt their transcriptional responses accordingly. While interplay between histone acetylation and deacetylation is critical for these functions, dysregulation during the aging process can lead to significant alterations in the neuroepigenetic landscape. These alterations contribute to impaired cognitive functions, neuronal cell death, and brain atrophy, all hallmarks of age-related neurodegenerative disease. Significantly, while age-related generation of DNA mutations remains irreversible, most neuroepigenetic PTMs are reversible. Thus, manipulation of the neural epigenome is proving to be an effective therapeutic strategy for neuroprotection in multiple types of age-related neurodegenerative disorders (NDs) that include Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS) and Huntington's disease (HD). Here, we highlight recent progress in research focusing on specific HAT-based neuroepigenetic mechanisms that underlie cognition and pathogenesis that is hallmarked in age-related NDs. We further discuss how these findings have potential to be translated into HAT-mediated cognitive-enhancing therapeutics to treat these debilitating disorders.},
}

Humans
*Neurodegenerative Diseases/therapy/enzymology/drug therapy
*Histone Acetyltransferases/metabolism
*Cognition/physiology
Animals
Protein Processing, Post-Translational
Histones/metabolism
Epigenesis, Genetic
Acetylation
Aging

@article {pmid40558496,
year = {2025},
author = {Varrone, A and Sousa, VC and Mugnaini, M and Biesinger, S and Nordvall, G and Kingston, L and Guzzetti, I and Elmore, CS and Sunnemark, D and Saturnino Guarino, D and Finnema, SJ and Schou, M},
title = {Development and In Vitro Characterization of [[3]H]GMC-058 as Radioligand for Imaging Parkinsonian-Related Proteinopathies.},
journal = {Cells},
volume = {14},
number = {12},
pages = {},
doi = {10.3390/cells14120869},
pmid = {40558496},
issn = {2073-4409},
support = {10908//Michael J Fox Foundation for Parkinson Research/ ; 1268/20//Swedish Parkinson Foundation (Parkinsonfonden)/ ; },
mesh = {Humans ; *Parkinson Disease/diagnostic imaging/metabolism/pathology ; *alpha-Synuclein/metabolism ; Brain/metabolism/pathology/diagnostic imaging ; Aged ; Alzheimer Disease/diagnostic imaging/metabolism ; Male ; Autoradiography ; Ligands ; Female ; *Radiopharmaceuticals ; },
abstract = {The molecular imaging of α-synuclein (α-syn) pathology in Parkinson's disease (PD) and related movement disorders is a clinically unmet need. The aim of this study was to discover and characterize in vitro a radioligand for imaging α-syn pathology. A library of 78 small molecules was developed and screened using recombinant α-syn fibrils and brain homogenates from Alzheimer's disease (AD) donors. The selection criteria were as follows: Kiα-syn < 30 nM, Kitau and KiA-β > 200 nM. Three compounds, GMC-073 (Kiα-syn: 8 nM), GMC-098 (Kiα-syn: 9.7 nM), and GMC-058 (Kiα-syn: 22.5 nM), fulfilled the criteria and were radiolabeled with [3]H. [[3]H]GMC-058 was the only compound with negligible binding in controls, and was further evaluated using tissue microarrays, autoradiography on fresh-frozen brain slices, and in vitro saturation binding assay on brain homogenates. [[3]H]GMC-058 binding co-localized with α-syn inclusions in Parkinson's disease (PD) and multiple-system atrophy (MSA), with dense A-β plaques in cerebral amyloid angiopathy and AD and with p-tau inclusions in progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). Specific binding was highest in PSP and CBD. In vitro KD was highest in AD (5.4 nM), followed by PSP (41 nM) and CBD (75 nM). The KD in MSA, PD, and controls was >100 nM. [[3]H]GMC-058 is a novel radioligand displaying a low affinity for aggregated α-syn in tissue, with an in vitro profile also suitable for detecting tau pathology in 4R tauopathies.},
}

Humans
*Parkinson Disease/diagnostic imaging/metabolism/pathology
*alpha-Synuclein/metabolism
Brain/metabolism/pathology/diagnostic imaging
Aged
Alzheimer Disease/diagnostic imaging/metabolism
Male
Autoradiography
Ligands
Female
*Radiopharmaceuticals

@article {pmid40558456,
year = {2025},
author = {Arpaia, P and Cacciapuoti, M and Cataldo, A and Criscuolo, S and De Benedetto, E and Masciullo, A and Pesola, M and Schiavoni, R},
title = {Assessing the Role of EEG Biosignal Preprocessing to Enhance Multiscale Fuzzy Entropy in Alzheimer's Disease Detection.},
journal = {Biosensors},
volume = {15},
number = {6},
pages = {},
doi = {10.3390/bios15060374},
pmid = {40558456},
issn = {2079-6374},
support = {B89J23002490005//Italian Ministry of Enterpise and Made in Italy/ ; B69J23001290005//Italian Ministry of Enterpise and Made in Italy/ ; PNRR DM 351/2022 - M4C1//Italian Ministry of University and Research/ ; },
mesh = {*Alzheimer Disease/diagnosis ; *Electroencephalography/methods ; Humans ; Entropy ; Fuzzy Logic ; Support Vector Machine ; *Signal Processing, Computer-Assisted ; Algorithms ; },
abstract = {Quantitative electroencephalography (QEEG) has emerged as a promising tool for detecting Alzheimer's disease (AD). Among QEEG measures, Multiscale Fuzzy Entropy (MFE) shows great potential in identifying AD-related changes in EEG complexity. However, MFE is intrinsically linked to signal amplitude, which can vary substantially among EEG systems, and this hinders the adoption of this metric for AD detection. To overcome this issue, this study investigates different preprocessing strategies to make the calculation of MFE less dependent on the specific amplitude characteristics of the EEG signals at hand. This contributes to generalizing and making more robust the adoption of MFE for AD detection. To demonstrate the robustness of the proposed preprocessing methods, binary classification tasks with Support Vector Machines (SVMs), Random Forest (RF), and K-Nearest Neighbor (KNN) classifiers are used. Performance metrics, such as classification accuracy and Matthews Correlation Coefficient (MCC), are employed to assess the results. The methodology is validated on two public EEG datasets. Results show that amplitude transformation, particularly normalization, significantly enhances AD detection, achieving mean classification accuracy values exceeding 80% with an uncertainty of 10% across all classifiers. These results highlight the importance of preprocessing in improving the accuracy and the reliability of EEG-based AD diagnostic tools, offering potential advancements in patient management and treatment planning.},
}

*Alzheimer Disease/diagnosis
*Electroencephalography/methods
Humans
Entropy
Fuzzy Logic
Support Vector Machine
*Signal Processing, Computer-Assisted
Algorithms

@article {pmid40558428,
year = {2025},
author = {De Silva, PIT and Hiniduma, K and Canete, R and Bhalerao, KS and Shawky, SM and Gunathilaka, H and Rouge, JL and Mosa, IM and Steffens, DC and Manning, K and Diniz, BS and Rusling, JF},
title = {Multiplexed CRISPR Assay for Amplification-Free Detection of miRNAs.},
journal = {Biosensors},
volume = {15},
number = {6},
pages = {},
doi = {10.3390/bios15060346},
pmid = {40558428},
issn = {2079-6374},
support = {2231490//U.S. National Science Foundation/ ; },
mesh = {*MicroRNAs/blood/analysis ; Humans ; *Biosensing Techniques ; *CRISPR-Cas Systems ; Limit of Detection ; },
abstract = {CRISPR-Cas proteins from bacteria are powerful tools for gene editing and molecular diagnostics. Expanding capacity of CRISPR to low cost, multiplexed assays of biomarkers is a key to future disease diagnostics, since multiple biomarker detection is essential for reliable diagnostics. Herein we describe a multiplexed assay in a 3D-printed 96-well plate with CRISPR-Cas13a immobilized in each well to target three circulating blood biomarker microRNAs (miRNAs 34c-5p, 200c-3p, and 30e-5p) for Alzheimer's disease (ALZ). Immobilized Cas13a is equipped with different crRNAs complementary to each miRNA target. MiRNA binding to crRNA complements activates the collateral RNase activity of Cas13a, cleaving a quenched fluorescent reporter (RNaseAlert) with fluorophore and quencher connected by an RNA oligonucleotide to enable fluorescence measurements. We achieved ultralow limits of detection (LOD) of 0.74 fg/mL for miRNA 34c-5p, 0.70 fg/mL for miRNA 30e-5p, and 7.4 fg/mL for miRNA 200c-3p, with dynamic ranges from LODs up to about 1800 pg/mL. The accuracy of the assay was validated by spike-recovery studies and good correlation of levels of patient plasma samples vs. a referee method. This new approach provides selective, sensitive multiplex miRNA biosensing, and simultaneously accommodates analysis of standards and controls.},
}

*MicroRNAs/blood/analysis
Humans
*Biosensing Techniques
*CRISPR-Cas Systems
Limit of Detection

@article {pmid40558228,
year = {2025},
author = {Niculescu, V and Dimitriu, AL and Nistor-Cseppento, DC and Tirla, S and Gherle, A and Uivaraseanu, B and Burnei, C},
title = {Multicenter Study of Comorbidities in Patients with Periprosthetic Fractures After Total Hip Arthroplasty and Their Association with Immediate Postoperative Complications.},
journal = {Clinics and practice},
volume = {15},
number = {6},
pages = {},
doi = {10.3390/clinpract15060110},
pmid = {40558228},
issn = {2039-7275},
abstract = {Background/Objectives: Periprosthetic fractures (PFs) can occur in both the upper and lower limbs, commonly resulting from falls at the same level. The frequency of PFs following total hip arthroplasty (THA) ranges from 0.045% to 4.1%, and this incidence is influenced by several factors, including age, gender, the type of prosthesis used, and existing comorbidities. Previous studies on this subject have been small in scale and did not adequately address the associated comorbidities, which pose a challenge for the aging population. This study aims to comparatively assess the incidence of THA-related PFs, immediate postoperative complications, and comorbidities in patients with PFs from three emergency hospitals. Methods: A retrospective observational study was conducted from 1 January to 31 December 2024, in which 54 patients with PFs hospitalized in three emergency hospitals (Bucharest, Oradea, and Ploiești) were evaluated, divided into Group B (n = 29), Group O (n = 14), and Group P (n = 11). Results: Of all patients with PFs, 81.48% had minor complications-grade 1, 9.26% had grade 2 complications (complications requiring medical treatment or other minor interventions), and 3.70% had complications requiring surgery or invasive procedures. Clavien-Dindo grade 5 (patient death) had an incidence of 3.70%. Cardiac pathology was the most common pathology; hypertension predominated in Group O (42.85%). Alzheimer's disease was associated in 7 patients (12.96%). Without associated pathology, about 13% of patients were identified. Diabetes mellitus also occurred frequently in 31.50%. Data analysis indicates a very weak positive correlation between the Dindo Index and the Charlson Comorbidity Index (r = 0.046), which is not statistically significant (p = 0.628). The effect size, measured by Fisher's z, is also reported as 0.046. Conclusions: No significant differences were found among the evaluated centers regarding therapeutic approaches, postoperative complications, and associated comorbidities. Furthermore, there is insufficient evidence to suggest a significant association between the Charlson Comorbidity Index and the Clavien-Dindo Index.},
}

@article {pmid40558015,
year = {2025},
author = {Tanaka, T and Suzuki, H and Taruta, H and Saga, A and Li, G and Fujisawa, S and Kaneko, MK and Kato, Y},
title = {Development of a Novel Anti-human EphA1 Monoclonal Antibody, Ea1Mab-30, for Multiple Applications.},
journal = {Monoclonal antibodies in immunodiagnosis and immunotherapy},
volume = {44},
number = {3},
pages = {41-52},
doi = {10.1089/mab.2025.0006},
pmid = {40558015},
issn = {2167-9436},
mesh = {Humans ; Animals ; *Receptor, EphA1/immunology/genetics ; CHO Cells ; Cricetulus ; *Antibodies, Monoclonal/immunology/biosynthesis ; Mice ; Caco-2 Cells ; Cricetinae ; Antibody Specificity/immunology ; Cell Line, Tumor ; },
abstract = {Erythropoietin-producing hepatocellular receptor A1 (EphA1) is one of the Eph receptor family members, the largest group of receptor tyrosine kinases. EphA1 is expressed in various tissues and regulates cellular homeostasis by interacting with its membrane-bound ephrin ligands and other receptors. EphA1 critically correlates with the pathogenesis in several disorders, including Alzheimer's disease and cancers. Therefore, establishing sensitive monoclonal antibodies (mAbs) for EphA1 has been desired for basic research, diagnosis, and treatment. In this study, a novel specific and sensitive anti-human EphA1 mAb, clone Ea1Mab-30 (mouse IgG1, kappa), was established by the Cell-Based Immunization and Screening (CBIS) method. Ea1Mab-30 demonstrated reactivity with an EphA1-overexpressed Chinese hamster ovary-K1 cell line (CHO/EphA1), an endogenously EphA1-expressing bladder carcinoma cell line (5637), and a colorectal adenocarcinoma cell line (Caco-2) in flow cytometry. Crossreactivities of Ea1Mab-30 with other Eph receptors were not observed. Furthermore, the values of apparent binding affinity for CHO/EphA1 and 5637 were determined to be 8.9 × 10[-9] M and 1.7 × 10[-9] M, respectively. Furthermore, Ea1Mab-30 detected EphA1 protein in CHO/EphA1 and 5637 lysates using Western blot analysis. Ea1Mab-30 also clearly stained EphA1 of formalin-fixed paraffin-embedded CHO/EphA1 using immunohistochemistry. Ea1Mab-30, established by CBIS method, could help analyze the EphA1-contributed cellular functions and have potential applications in pathological diagnosis and treatment with specificity and high affinity for EphA1-expressing cells.},
}

Humans
Animals
*Receptor, EphA1/immunology/genetics
CHO Cells
Cricetulus
*Antibodies, Monoclonal/immunology/biosynthesis
Mice
Caco-2 Cells
Cricetinae
Antibody Specificity/immunology
Cell Line, Tumor

@article {pmid40557877,
year = {2025},
author = {Wang, S and Sun, M and Zhang, Y and Wang, S and Wang, Z and Zhang, Z and Gao, Y and Lu, W and Wang, Y and Zhang, Y and Han, L},
title = {Concurrent Detection of Amyloid-β Biomarkers via Dual-Channel Graphene Field-Effect Transistor with Liquid-Metal Van Der Waals Contacts for Alzheimer Screening.},
journal = {ACS sensors},
volume = {},
number = {},
pages = {},
doi = {10.1021/acssensors.5c01060},
pmid = {40557877},
issn = {2379-3694},
abstract = {Early and accurate detection of Alzheimer's disease (AD) is demanding for timely interventions to slow disease progression. Graphene field-effect transistors (GFETs) are promising in AD biosensors due to their surface sensitivity, nonlabeling, and quick signal detection. Here, we developed a dual-channel GFET integrated with Galinstan liquid-metal electrodes. These electrodes establish van der Waals contacts with graphene, simplifying the manufacturing process by eliminating the need for high temperatures or significant energy inputs. This liquid metal electrodes reduce channel damage and significantly boost charge carrier mobility, with electron mobility reaching 5320 cm[2]·V[-1]·s[-1] and hole mobility at 5572 cm[2]·V[-1]·s[-1], surpassing traditional gold electrodes. The enhanced electrical performance of the Liquid metal GFET (LM-GFET) facilitates the highly sensitive and specific detection of Alzheimer's disease (AD) biomarkers. Its dual-channel configuration allows for the simultaneous detection of amyloid-β (Aβ) peptides Aβ40 and Aβ42, and the calculation of the Aβ42/Aβ40 ratio, providing a reliable marker for early stage AD diagnosis. The demonstrated robustness, stability, and improved performance position the LM-GFET as an effective tool for noninvasive AD diagnostics, underscoring its potential in advancing graphene-based biosensors for clinical use.},
}

@article {pmid40557760,
year = {2025},
author = {El-Ghazawi, K and Mills Iii, WA and Peirce, SM and Eyo, UB},
title = {Two-Photon Microscopy Functional Assays for Serial Imaging of Brain Microvessels and the Neurovascular Unit Through Disease Progression.},
journal = {Current protocols},
volume = {5},
number = {6},
pages = {e70167},
doi = {10.1002/cpz1.70167},
pmid = {40557760},
issn = {2691-1299},
mesh = {Animals ; *Microvessels/diagnostic imaging/pathology ; Mice ; *Brain/blood supply/diagnostic imaging ; Disease Progression ; *Microscopy, Fluorescence, Multiphoton/methods ; Astrocytes ; Microglia ; Pericytes ; },
abstract = {Microvascular impairments are a major issue in many diseases of the brain. In fact, they are often considered the earliest pathological phenomena in neurodegenerative diseases like Alzheimer's Disease or the locus of pathology as in stroke. Still, little is known about the mechanistic and cellular level events that contribute to these impairments. Given the importance of the neurovascular unit (NVU) in maintaining functional brain tissue, alterations to NVU cell types are important to study in the context of disease progression. With the use of two-photon microscopy, microvessels and cells can be imaged and evaluated throughout disease progression. Herein we aim to provide a comprehensive protocol for setting up and using two-photon microscopy for serial imaging of neurovascular unit cell types (i.e., pericytes, astrocytes, and microglia). We also describe interpreting results from cell and vessel changes based on disease or functional tests through multiple timepoints. © 2025 The Author(s). Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Mouse set up for serial, live 2-photon imaging Basic Protocol 2: Field of view acquisitions over multiple timepoints Basic Protocol 3: Line scan acquisitions for acquiring red blood cell metrics Basic Protocol 4: Quantitative measurements of vessel and cell changes Basic Protocol 5: Documenting changes in astrocyte morphology following induction of transient focal photothrombotic stroke using Rose Bengal.},
}

Animals
*Microvessels/diagnostic imaging/pathology
Mice
*Brain/blood supply/diagnostic imaging
Disease Progression
*Microscopy, Fluorescence, Multiphoton/methods
Astrocytes
Microglia
Pericytes

@article {pmid40557569,
year = {2025},
author = {Ye, Z and Li, L and Duan, Q and Sheng, X and Zhang, C and Fan, X and Li, Z and Xiao, L},
title = {KLVFF-Guided Molecular Scissors: a Trojan Horse Strategy for Precision Photodynamic Dissolution of Aβ Aggregates.},
journal = {Advanced healthcare materials},
volume = {},
number = {},
pages = {e2502595},
doi = {10.1002/adhm.202502595},
pmid = {40557569},
issn = {2192-2659},
support = {2024JJ3030//Natural Science Foundation of Hunan Province/ ; 22204147//National Natural Science Foundation of China/ ; },
abstract = {Alzheimer's disease (AD) is pathologically linked to the aggregation of amyloid-β (Aβ) peptides into neurotoxic fibrils. Despite advancements in Alzheimer's therapeutics, current strategies fail to simultaneously target amyloid-β aggregation and oxidative stress, particularly with spatiotemporal precision. To address the limitations of conventional therapies, this study develops a photo-responsive nanomaterial, conjugated polymer nanodots functionalized with chlorin e6 (Ce6) and KLVFF peptides (CNPs-Ce650-K0.5), for targeted inhibition of Aβ1-42 fibrillization. The nanomaterial is synthesized via nanoprecipitation, integrating Ce6 for reactive oxygen species (ROS) generation and KLVFF for Aβ-specific recognition. Systematic characterization confirms its structural stability, tunable ROS production, and high biocompatibility. Fluorescence microscopy, TEM, and CD spectroscopy demonstrate that CNPs-Ce650-K0.5 synergistically inhibits Aβ1-42 aggregation through dual mechanisms: 1) KLVFF-mediated high-affinity binding to Aβ monomers, preventing nucleation; 2) Ce6-generated ROS under light irradiation, destabilizing β-sheet structures. This work establishes CNPs-Ce650-K0.5 as a multifunctional platform for precise Aβ modulation, offering a promising strategy for AD therapeutics with spatiotemporal controllability and minimal off-target effects.},
}

@article {pmid40557283,
year = {2025},
author = {Liang, J and Xue, Z and Zhou, W and Guo, X and Wen, Y},
title = {Auto-branch multi-task learning for simultaneous prediction of multiple correlated traits associated with Alzheimer's disease.},
journal = {Frontiers in genetics},
volume = {16},
number = {},
pages = {1538544},
pmid = {40557283},
issn = {1664-8021},
abstract = {INTRODUCTION: Correlated phenotypes may have both shared and unique causal factors, and jointly modeling these phenotypes can enhance prediction performance by enabling efficient information transfer.

METHODS: We propose an auto-branch multi-task learning model within a deep learning framework for the simultaneous prediction of multiple correlated phenotypes. This model dynamically branches from a hard parameter sharing structure to prevent negative information transfer, ensuring that parameter sharing among phenotypes is beneficial.

RESULTS: Through simulation studies and analysis of seven Alzheimer's disease-related phenotypes, our method consistently outperformed Multi-Lasso model, single-task learning approaches, and commonly used hard parameter sharing models with predefine shared layers. These analyses also reveal that while genetic contributions across phenotypes are similar, the relative influence of each genetic factor varies substantially among phenotypes.},
}

@article {pmid40557139,
year = {2025},
author = {Trieu, C and van Leeuwenstijn, MSSA and Schlüter, LM and Ebenau, JL and Verberk, IMW and Sikkes, SAM and Verfaillie, SCJ and van de Giessen, E and Teunissen, CE and van der Flier, WM and van Harten, AC},
title = {Longitudinal associations between amyloid and symptoms of depression and anxiety in subjective cognitive decline: the impact of personality characteristics.},
journal = {Frontiers in psychiatry},
volume = {16},
number = {},
pages = {1572174},
pmid = {40557139},
issn = {1664-0640},
abstract = {INTRODUCTION: Depressive/anxiety symptoms are common in subjective cognitive decline (SCD) and may relate to Alzheimer's pathology, potentially modulated by personality characteristics.

METHODS: Depressive/anxiety symptoms were assessed over 4 ± 2 years in 329 SCD (88 amyloid-positive/241 amyloid-negative) using Geriatric Depression Scale-15 (GDS), Center for Epidemiological Studies-Depression (CES-D), and Hospital Anxiety and Depression Scale-Anxiety (HADS-A). Mixed-effects models assessed associations between amyloid status and these symptoms, with neuroticism and somatization as effect-modifiers.

RESULTS: Amyloid status was not directly associated with GDS, CES-D or HADS-A. However, neuroticism modified the association between amyloid status and GDS (p<0.05). In lower neuroticism, amyloid positivity was associated with GDS increase (β:0.10 ± 0.08), but not in higher neuroticism (β:-0.04 ± 0.12). Somatization modified the association between amyloid status and CES-D (p<0.05). In lower somatization, amyloid positivity was associated with CES-D increase (β:0.65 ± 0.23), but not in higher somatization (β:-0.12 ± 0.29).

DISCUSSION: Amyloid-positive individuals with lower neuroticism/somatization increased more in depressive symptoms over time, suggesting a preclinical AD-related depressive phenotype.},
}

@article {pmid40556904,
year = {2025},
author = {He, Z and Zhang, H and Hu, G and Qiao, Y and Yin, C and Li, J and Lin, H and Wu, A and Qin, D and Law, BY and Hu, G and Yu, L},
title = {The current status, trends, and challenges of Alzheimer's disease and other dementias in Asia (1990-2036).},
journal = {Frontiers in public health},
volume = {13},
number = {},
pages = {1583339},
pmid = {40556904},
issn = {2296-2565},
mesh = {Humans ; *Alzheimer Disease/epidemiology/mortality ; Female ; Asia/epidemiology ; Prevalence ; Aged ; Male ; *Dementia/epidemiology/mortality ; Risk Factors ; Disability-Adjusted Life Years/trends ; Aged, 80 and over ; Middle Aged ; Cost of Illness ; },
abstract = {BACKGROUND: With global aging, Alzheimer's disease (AD) and other dementias have emerged as significant health threats to the older adults, garnering considerable attention due to their impact on public health. Despite the substantial burden of dementia in Asia, targeted research remains limited. This study aims to assess the current burden, future trends, risk factors, and inequalities in Asia.

METHOD: The GBD 2021 study was utilized to evaluate the numbers and age-standardized rates (ASRs) of prevalence, mortality, and disability-adjusted life-years (DALYs) of AD and other dementias from 1990 to 2021. Joinpoint regression analysis was performed to assess the trends during this period, while the Autoregressive Integrated Moving Average (ARIMA) model was employed to predict future trends. Additionally, the relationship between disease burden and sociodemographic index (SDI) was also analyzed.

RESULTS: In 2021, Asia experienced a 250.44% increase in prevalent cases, a 297.34% rise in mortality, and a 249.54% surge in DALYs for AD and other dementias compared to 1990. Meanwhile, the age-standardized prevalence rate, age-standardized mortality rate, and age-standardized DALY rate also exhibited varying degrees of rise from 1990 to 2021. Demographically, the disease burden was higher in women and those aged 65 and above. Regionally, the burden was highest in East Asia and relatively low in South and Central Asia. Nationally, China, India, Japan, and Indonesia reported the most cases. Over the next 15 years, the age-standardized prevalence rate in Asia is expected to peak in 2028 before declining, while the age-standardized mortality rate is anticipated to keep rising. An overall "V" shaped association was found between sociodemographic index (SDI) and the age-standardized DALY rate in Asia. Only smoking, high fasting plasma glucose (FPG), and high BMI were identified as causal risk factors within the GBD framework.

CONCLUSION: The burden of AD and other dementias in Asia has significantly increased over the past three decades and is expected to persistently impact Asian populations, particularly in developing countries experiencing rapid demographic shifts. Women and the older adult should be a focus of attention. It is imperative to implement targeted prevention and intervention strategies, enhance chronic disease management, and control risk factors.},
}

Humans
*Alzheimer Disease/epidemiology/mortality
Female
Asia/epidemiology
Prevalence
Aged
Male
*Dementia/epidemiology/mortality
Risk Factors
Disability-Adjusted Life Years/trends
Aged, 80 and over
Middle Aged
Cost of Illness

@article {pmid40556738,
year = {2025},
author = {Golovynska, I and Chen, Q and Stepanov, YV and Lin, D and Qu, J},
title = {Amyloid-induced mitochondrial network disruption in neurons monitored by STED super-resolution imaging.},
journal = {Frontiers in cell and developmental biology},
volume = {13},
number = {},
pages = {1610204},
pmid = {40556738},
issn = {2296-634X},
abstract = {INTRODUCTION: Disruptions in mitochondrial metabolism are accompanied by morphological changes in mitochondrial network caused by amyloid-beta (Aβ). In the study, mitochondrial network analysis is performed using stimulated emission depletion (STED) super-resolution fluorescence microscopy to examine alterations in neurons exposed to Aβ in vitro.

METHODS: A detailed analysis of mitochondrial network in healthy neurons and those exposed to Aβ is performed using STED compared to conventional laser-scanning confocal fluorescence microscopy. The functional analysis is applied to mitochondrial volume, surface area, branch length, diameter, junctions, and endpoints. Neurons incubated with or without Aβ were also stained with fluorescent mitochondrial function indicators.

RESULTS: In neurons exposed to Aβ, the number of mitochondria increases by 2.6 times, while their total volume decreases by 2.2 times. As a result, the volume and surface area per mitochondrion decrease by 6-fold and 4-fold, respectively. Increases in sphericity, branch diameter, and donut-like structures are observed. The total mitochondrial length is 3.7-fold reduced, while the number of branches is 2.5-fold decreased, and the branch count is 7.5-fold reduced. Additional measurements reveal decreased mitochondrial membrane potential, increased reactive oxygen species generation, and reduced cell viability. This may indicate that Aβ exposure causes significant oxidative stress, mitochondrial integrity loss, and ultimately neuronal death.

CONCLUSION: Aβ induces mitochondrial fragmentation, thickening, increased sphericity, and deformation of mitochondrial matrix in neurons. The results provide insights into the impact of Aβ on neurons and show the aptitude of the high-resolution STED microscopy diagnostic tool for neurodegenerative diseases.},
}

@article {pmid40556661,
year = {2025},
author = {Ahammad, RU and Spencer, B and Quach, B and Salehi, S and Rissman, RA},
title = {A splice-switching antisense oligonucleotide targeting APP reduces accumulation of α-synuclein in a mouse model of Parkinson's disease.},
journal = {Alzheimer's & dementia (New York, N. Y.)},
volume = {11},
number = {2},
pages = {e70117},
pmid = {40556661},
issn = {2352-8737},
abstract = {INTRODUCTION: Alzheimer's disease (AD) and Parkinson's disease (PD) are neurodegenerative disorders characterized by abnormal protein aggregation, with amyloid beta (Aβ) and α-synuclein (α-syn) as key pathological markers. Increasing evidence highlights a pathological interplay between Aβ and α-syn, exacerbating neurodegeneration in both AD and PD. In this study, we evaluated the effects of reducing amyloid precursor protein (APP) processing on α-syn pathology using a splice-switching oligonucleotide (SSO) targeting APP exon 15 in Thy1-α-syn transgenic (α-syn-tg) mice.

METHODS: α-syn-tg mice received systemic APP SSO treatment. Immunohistochemistry and immunoblotting assessed α-syn, phosphorylated α-syn (P-Syn), and APP C-terminal fragments (CTFs) in the cortex, hippocampus, and thalamus. Neuronal integrity in different brain regions were examined, and behavioral assessments evaluated cognitive and motor functions.

RESULTS: APP SSO treatment significantly reduced α-syn and P-Syn in the cortex, hippocampus, and thalamus while also reversing neuronal loss in the hippocampal CA3 region. Interestingly, α-syn-tg mice exhibited elevated levels of alternative APP CTFs, which were reduced by APP SSO treatment, implicating APP processing dysregulation in α-syn pathology. Although behavioral assessments revealed no significant impairments or improvements in female α-syn-tg mice.

DISCUSSION: Our findings demonstrate that targeting APP reduces α-syn pathology and rescues neuronal loss, supporting the therapeutic potential of APP modulation in synucleinopathies. While no behavioral changes were observed in transgenic mice, further research exploring different models and conditions may provide additional insights into the full range of therapeutic benefits. Future studies should optimize delivery methods and explore combination therapies to enhance outcomes in neurodegenerative diseases with overlapping proteinopathies.

HIGHLIGHTS: APP-targeting SSO reduces α-syn and P-Syn in α-syn-tg mice.APP SSO lowers APP CTFs, linking APP processing to α-syn pathology.Neuronal loss in the hippocampal CA3 region is restored following APP SSO treatment.Behavioral assessments show no significant changes in female α-syn-tg mice.Findings support APP modulation as a potential strategy for synucleinopathies.},
}

@article {pmid40556653,
year = {2025},
author = {Lan, Y and Ding, J and Yu, T and Cheng, C},
title = {Research progress of platelets in neurodegenerative diseases.},
journal = {Frontiers in aging neuroscience},
volume = {17},
number = {},
pages = {1544605},
pmid = {40556653},
issn = {1663-4365},
abstract = {Neurodegenerative disease (NDD) is a disease state characterized by the loss of neuronal cells in the brain and spinal cord, including Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS). They have become a major challenge for the world's health system in the twenty-first century, with an increasing incidence year by year, complex and diverse causes, and a lack of effective therapeutic. The brain and spinal cord are composed of neurons, and activated platelets are highly similar to neurons. The occurrence and development of these diseases are often accompanied by platelet activation, suggesting that platelets play an important role in the pathological process of NDDs. This article reviews the research progress of platelets in common NDDs, and elaborates on the mechanisms of platelets' involvement in NDDs and the use as a therapeutic option for NDDs to providing new ideas for the diagnosis and treatment of NDDs.},
}

@article {pmid40556526,
year = {2025},
author = {Yener, K and Hayat, A},
title = {Evaluation of the effects of tideglusib and calcium sulfate on the healing of experimental bone defects in rabbits.},
journal = {Polish journal of veterinary sciences},
volume = {28},
number = {2},
pages = {213-223},
doi = {10.24425/pjvs.2025.154940},
pmid = {40556526},
issn = {2300-2557},
mesh = {Animals ; Rabbits ; *Calcium Sulfate/pharmacology/therapeutic use/administration & dosage ; Bone Regeneration/drug effects ; Bone Transplantation/veterinary ; Wound Healing/drug effects ; Male ; },
abstract = {This study aimed to evaluate the effects of tideglusib and bone graft mixture on bone healing. Tideglusib is a drug used in the treatment of various neurological disorders such as Alzheimer's disease. In a relevant study, the positive effect of tideglusib on the Wnt pathway, one of the pathways involved in bone regeneration and dentin tissue regeneration, was demonstrated. Dentin and bone tissues have structurally similar healing mechanisms. Therefore, tideglusib may have a similar effect on the bone tissue. The main goal of bone grafting is to provide bone regeneration and functional healing through remodeling. Bone graft materials are divided into four types based on their source: autogenous, allogenous, xenogenous, and alloplastic. Because these graft materials have various advantages and disadvantages, research continues to focus on alternative materials and applications. Sixteen New Zealand rabbits were included in this study. A unicortical 3.5 mm diameter defect was created in the tibia of rabbits under general anesthesia. The groups in the study were as follows: Group 1, left proximal tibia defect area was controlled (defect area was left empty); Group 2, left distal tibia defect area was treated with tideglusib + calcium sulfate; Group 3, right proximal tibia defect area was treated with calcium sulfate only; Group 4, right distal tibia defect area was treated with tideglusib only. Mediolateral (M/L) radiographs of the tibia were taken on the 30th and 60th postoperative days. On the 30th day, the first eight rabbits were sacrificed, and on the 60th day, the remaining eight were sacrificed for histopathological examination. New bone formation in the obtained samples was evaluated by radiological and histopathological analyses. The study concluded that the combination of tideglusib and calcium sulfate significantly enhanced bone healing compared with the other groups (p<0.005). This suggests that tideglusib, either alone or in combination with bone graft materials, could serve as a promising alternative for the repair of bone defects.},
}

Animals
Rabbits
*Calcium Sulfate/pharmacology/therapeutic use/administration & dosage
Bone Regeneration/drug effects
Bone Transplantation/veterinary
Wound Healing/drug effects
Male

@article {pmid40556345,
year = {2025},
author = {Hu, Y and Niu, L and Chen, Y and Yang, H and Qiu, X and Jiang, F and Liu, C and Cai, H and Le, W},
title = {Voluntary wheel running exercise improves sleep disorder, circadian rhythm disturbance, and neuropathology in an animal model of Alzheimer's disease.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21},
number = {6},
pages = {e70314},
doi = {10.1002/alz.70314},
pmid = {40556345},
issn = {1552-5279},
support = {32220103006//National Natural Science Foundation of China/ ; 82271524//National Natural Science Foundation of China/ ; 2024ZDJH01PT066//life and health guidance program of Dalian city/ ; HC//the intramural research program of National Institute on Aging, NIH/ ; AG000540//the intramural research program of National Institute on Aging, NIH/ ; YDZX20213100001002//Fundamental Research Funds for Central Universities of the Central South University/ ; },
mesh = {Animals ; *Alzheimer Disease/pathology/complications/therapy ; Disease Models, Animal ; *Physical Conditioning, Animal/physiology ; Mice, Transgenic ; *Sleep Wake Disorders/etiology/pathology/therapy ; Mice ; *Chronobiology Disorders/etiology/pathology/therapy ; Male ; *Brain/pathology/metabolism ; Suprachiasmatic Nucleus/pathology/metabolism ; Mice, Inbred C57BL ; Circadian Rhythm/physiology ; },
abstract = {INTRODUCTION: The sleep-wake cycle and circadian rhythm disturbances are common in Alzheimer's disease (AD). However, it is not known if exercise has any benefit for the sleep disorders in AD.

METHODS: We conducted a 2-month voluntary wheel running (VWR) exercise (Ex) in an animal model of AD (APP[SWE]/PS1[dE9] mice). We assessed behavioral circadian rhythm, sleep structure, circadian clock genes, cognitive function, and neurodegeneration in the suprachiasmatic nucleus (SCN), the hippocampus, and the cortex.

RESULTS: After VWR exercise in the AD mice, the rapid eye movement sleep was increased by 89%. The levels of circadian clock genes were significantly changed (brain and muscle arnt-like protein 1 [BMAL1] and retinoic acid receptor-related orphan receptorsα [RORα] reduced by 45.7% and 36.4%, reverse erythroblastosis virusα (REV-ERBα) increased by 119%) in the SCN by immunofluorescence staining, with the mRNA levels were markedly altered (Bmal1 and Rorα decreased by 57% and 68%, Rev-erbα elevated by 79%) in the hypothalamus at Zeitgeber Time 1; phospho-tau 231 (p-tau231) was reduced by 35%, whereas vesicular GABA transporter (VGAT) was elevated by 38.7% in the SCN. In addition, ionized calcium binding adapter molecude 1 (Iba1), glial fibrillary acidic protein (GFAP), amyloid β (Aβ), and p-tau231 were significantly reduced in the hippocampus and cortex.

DISCUSSION: Our results demonstrate that VWR exercise improves sleep disorders, cognitive deficits, and neuropathology in AD mice.

HIGHLIGHTS: Voluntary wheel running (VWR) exercise improves the behavioral circadian rhythm disorder and sleep structure disturbance in Alzheimer's disease (AD) mice. After VWR exercise, there is a significant change in the expression levels of circadian clock genes, and a remarkable reduction of tau phosphorylation and axonal damage in the γ-aminobutyric acid (GABA)ergic neurons in the suprachiasmatic nucleus (SCN). The levels of beta-site amyloid precurson protein cleaving enzyme 1 (BACE1) and glycogen synthase kinase-3β (GSK3β) are reduced in the hypothalamus after VWR exercise in AD mice. Furthermore, VWR exercise attenuates cognitive deficits, neuroinflammation, amyloid beta (Aβ), and phospho-tau protein accumulation in the hippocampus and cortex.},
}

Animals
*Alzheimer Disease/pathology/complications/therapy
Disease Models, Animal
*Physical Conditioning, Animal/physiology
Mice, Transgenic
*Sleep Wake Disorders/etiology/pathology/therapy
Mice
*Chronobiology Disorders/etiology/pathology/therapy
Male
*Brain/pathology/metabolism
Suprachiasmatic Nucleus/pathology/metabolism
Mice, Inbred C57BL
Circadian Rhythm/physiology

@article {pmid40556318,
year = {2025},
author = {Bradley, J and Pottier, C and da Fonseca, EL and Kurup, JT and Western, D and Wang, C and Neupane, A and Ray, NR and Jean-Francois, M and Ali, M and Timsina, J and Bergmann, K and Budde, J and Martin, ER and Pericak-Vance, MA and Cuccaro, M and Naj, AC and Kunkle, BW and , and Schellenberg, GD and Fernandez, V and Haines, J and Morris, JC and Holtzman, DM and Perrin, RJ and Reitz, C and Beecham, GW and Cruchaga, C},
title = {Novel early-onset Alzheimer-associated genes influence risk through dysregulation of glutamate, immune activation, and intracellular signaling pathways.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21},
number = {6},
pages = {e70377},
doi = {10.1002/alz.70377},
pmid = {40556318},
issn = {1552-5279},
support = {R01AG044546/NH/NIH HHS/United States ; P01AG003991/NH/NIH HHS/United States ; RF1AG053303/NH/NIH HHS/United States ; RF1AG058501/NH/NIH HHS/United States ; U01AG058922/NH/NIH HHS/United States ; RF1AG074007/NH/NIH HHS/United States ; R00AG062723/NH/NIH HHS/United States ; P30 AG066515/NH/NIH HHS/United States ; //Chan Zuckerberg Initiative/ ; //Michael J. Fox Foundation/ ; W81XWH-12-2-0012//Department of Defense/ ; ZEN-22-848604//Alzheimer's Association Zenith Fellows Award/ ; U01 AG032984/AG/NIA NIH HHS/United States ; RC2 AG036528/AG/NIA NIH HHS/United States ; AG052410/AG/NIA NIH HHS/United States ; U24 AG21886//National Cell Repository for Alzheimer's Disease/ ; //National Institute on Aging Alzheimer's Disease Data Storage Site/ ; U24-AG041689//University of Pennsylvania/ ; U54 AG052427/AG/NIA NIH HHS/United States ; U24 AG072122/AG/NIA NIH HHS/United States ; U24 AG026395/AG/NIA NIH HHS/United States ; U24 AG026390//University of Pennsylvania/ ; R01AG041797//University of Pennsylvania/ ; P30 AG019610/AG/NIA NIH HHS/United States ; P30 AG013846/AG/NIA NIH HHS/United States ; U01 AG10483//Boston University/ ; R01 CA129769/CA/NCI NIH HHS/United States ; R01 MH080295/MH/NIMH NIH HHS/United States ; R01 AG017173/AG/NIA NIH HHS/United States ; R01 AG025259/AG/NIA NIH HHS/United States ; R01 AG048927/AG/NIA NIH HHS/United States ; R01AG33193//Boston University/ ; R01 AG009029/AG/NIA NIH HHS/United States ; P50 AG008702/AG/NIA NIH HHS/United States ; R37 AG015473/AG/NIA NIH HHS/United States ; R01 AG037212/AG/NIA NIH HHS/United States ; R01 AG028786/AG/NIA NIH HHS/United States ; P30 AG028377/AG/NIA NIH HHS/United States ; AG05128//Duke University/ ; AG025688//Emory University/ ; UO1 AG006781//Group Health Research Institute/ ; UO1 HG004610//Group Health Research Institute/ ; UO1 HG006375//Group Health Research Institute/ ; U01 HG008657/HG/NHGRI NIH HHS/United States ; P30 AG10133//Indiana University/ ; R01 AG009956/AG/NIA NIH HHS/United States ; RC2 AG036650/AG/NIA NIH HHS/United States ; P50 AG005146/AG/NIA NIH HHS/United States ; R01 AG020688/AG/NIA NIH HHS/United States ; P50 AG005134/AG/NIA NIH HHS/United States ; P50 AG016574/AG/NIA NIH HHS/United States ; R01 AG032990/AG/NIA NIH HHS/United States ; KL2 RR024151/RR/NCRR NIH HHS/United States ; P50 AG005138/AG/NIA NIH HHS/United States ; P01 AG002219/AG/NIA NIH HHS/United States ; P30 AG08051//New York University/ ; UL1 RR029893/RR/NCRR NIH HHS/United States ; 5R01AG012101//New York University/ ; 5R01AG022374//New York University/ ; 5R01AG013616//New York University/ ; 1RC2AG036502//New York University/ ; 1R01AG035137//New York University/ ; P20 MD000546/MD/NIMHD NIH HHS/United States ; R01 AG28786-01A1//North Carolina A&T University/ ; P30 AG013854/AG/NIA NIH HHS/United States ; P30 AG008017/AG/NIA NIH HHS/United States ; R01 AG026916/AG/NIA NIH HHS/United States ; P30 AG010161/AG/NIA NIH HHS/United States ; R01 AG019085/AG/NIA NIH HHS/United States ; R01 AG15819//Rush University/ ; R01 AG17917//Rush University/ ; R01 AG030146/AG/NIA NIH HHS/United States ; R01 AG01101//Rush University/ ; RC2 AG036650/AG/NIA NIH HHS/United States ; R01 AG22018//Rush University/ ; R01 NS059873/NS/NINDS NIH HHS/United States ; P50 AG016582/AG/NIA NIH HHS/United States ; R01 AG031581/AG/NIA NIH HHS/United States ; P30 AG010129/AG/NIA NIH HHS/United States ; P50 AG016573/AG/NIA NIH HHS/United States ; P50 AG016570/AG/NIA NIH HHS/United States ; P50 AG005131/AG/NIA NIH HHS/United States ; P50 AG023501/AG/NIA NIH HHS/United States ; P01 AG019724/AG/NIA NIH HHS/United States ; P30 AG028383/AG/NIA NIH HHS/United States ; AG05144//University of Kentucky/ ; P50 AG008671/AG/NIA NIH HHS/United States ; P30 AG010124/AG/NIA NIH HHS/United States ; P50 AG005133/AG/NIA NIH HHS/United States ; AG030653//University of Pittsburgh/ ; AG041718//University of Pittsburgh/ ; AG07562//University of Pittsburgh/ ; AG02365//University of Pittsburgh/ ; P50 AG005142/AG/NIA NIH HHS/United States ; P30 AG012300/AG/NIA NIH HHS/United States ; R01 AG027944/AG/NIA NIH HHS/United States ; AG010491//University of Miami/ ; AG027944//University of Miami/ ; AG021547//University of Miami/ ; AG019757//University of Miami/ ; P50AG005136//University of Washington/ ; R01AG042437//University of Washington/ ; P50AG033514//University of Wisconsin/ ; R01AG019085//Vanderbilt University/ ; P50AG005681//Washington University/ ; P01AG03991//Washington University/ ; P01AG026276//Washington University/ ; //Kathleen Price Bryan Brain Bank at Duke University Medical Center/ ; IIRG-08-89720//Glaxo Smith Kline/ ; IIRG-05-14147//Glaxo Smith Kline/ ; //US Department of Veterans Affairs Administration/ ; //Office of Research and Development/ ; //Biomedical Laboratory Research Program/ ; A2111048//BrightFocus Foundation/ ; /WT_/Wellcome Trust/United Kingdom ; /HHMI/Howard Hughes Medical Institute/United States ; //the Canadian Institute of Health Research/ ; AG041232//Kronos Science/ ; //The Banner Alzheimer's Foundation/ ; //Johnnie B. Byrd Sr. Alzheimer's Institute/ ; /MRC_/Medical Research Council/United Kingdom ; //Newcastle Brain Tissue Resource/ ; //local NHS trusts and Newcastle University/ ; //London Brain Bank for Neurodegenerative Diseases/ ; //South West Dementia Brain Bank/ ; //Higher Education Funding Council for England (HEFCE), Alzheimer's Research Trust (ART)/ ; //BRACE/ ; //North Bristol NHS Trust Research and Innovation Department and DeNDRoN/ ; //Netherlands Brain Bank/ ; //Stichting MS Research/ ; //Brain Net Europe/ ; //Hersenstichting Nederland Breinbrekend Werk/ ; //International Parkinson Fonds/ ; //Internationale Stiching Alzheimer Onderzoek/ ; //Institut de Neuropatologia/ ; //Servei Anatomia Patologica/ ; //Universitat de Barcelona/ ; /EB/NIBIB NIH HHS/United States ; //AbbVie/ ; /ALZ/Alzheimer's Association/United States ; //Alzheimer's Drug Discovery Foundation/ ; //Araclon Biotech/ ; //CereSpir, Inc./ ; //Eisai Inc./ ; //Elan Pharmaceuticals, Inc./ ; //EuroImmun/ ; //GE Healthcare/ ; //IXICO Ltd./ ; //Janssen Alzheimer Immunotherapy Research & Development, LLC./ ; //Johnson & Johnson Pharmaceutical Research & Development LLC./ ; //Lumosity/ ; //Meso Scale Diagnostics, LLC./ ; //NeuroRx Research/ ; //Neurotrack Technologies/ ; //Piramal Imaging/ ; //Servier/ ; //Takeda Pharmaceutical Company/ ; //Transition Therapeutics/ ; //Northern California Institute for Research and Education/ ; //Alzheimer's Disease Cooperative Study/ ; P30AG066444//Laboratory for Neuro Imaging at the University of Southern California/ ; P01AG03991//Laboratory for Neuro Imaging at the University of Southern California/ ; P01AG026276//Laboratory for Neuro Imaging at the University of Southern California/ ; //the Hope Center for Neurological Disorders/ ; //NeuroGenomics and Informatics Center/ ; //Departments of Neurology and Psychiatry at Washington University School of Medicine/ ; //Genotype-Tissue Expression (GTEx/ ; P30AG10161//Accelerating Medicines Partnership (AMP-AD)/ ; P30AG72975//Accelerating Medicines Partnership (AMP-AD)/ ; R01AG15819//Accelerating Medicines Partnership (AMP-AD)/ ; R01AG17917//Accelerating Medicines Partnership (AMP-AD)/ ; R01AG036836//Accelerating Medicines Partnership (AMP-AD)/ ; U01AG46152//Accelerating Medicines Partnership (AMP-AD)/ ; U01AG61356//Accelerating Medicines Partnership (AMP-AD)/ ; U01AG046139//Accelerating Medicines Partnership (AMP-AD)/ ; P50AG016574//Accelerating Medicines Partnership (AMP-AD)/ ; R01AG032990//Accelerating Medicines Partnership (AMP-AD)/ ; U01AG046139//Accelerating Medicines Partnership (AMP-AD)/ ; R01AG018023//Accelerating Medicines Partnership (AMP-AD)/ ; U01AG006576//Accelerating Medicines Partnership (AMP-AD)/ ; U01AG006786//Accelerating Medicines Partnership (AMP-AD)/ ; R01AG025711//Accelerating Medicines Partnership (AMP-AD)/ ; R01AG017216//Accelerating Medicines Partnership (AMP-AD)/ ; R01AG003949//Accelerating Medicines Partnership (AMP-AD)/ ; R01NS080820//Accelerating Medicines Partnership (AMP-AD)/ ; U24NS072026//Accelerating Medicines Partnership (AMP-AD)/ ; P30AG19610//Accelerating Medicines Partnership (AMP-AD)/ ; U01AG046170//Accelerating Medicines Partnership (AMP-AD)/ ; RF1AG057440//Accelerating Medicines Partnership (AMP-AD)/ ; U24AG061340//Accelerating Medicines Partnership (AMP-AD)/ ; //Cure PSP/ ; //Mayo and Michael J Fox foundations/ ; //Arizona Department of Health Services and the Arizona Biomedical Research Commission/ ; //Sun Health Research Institute Brain and Body Donation Program/ ; //Mayo Clinic Brain Bank/ ; //Mount Sinai/JJ Peters VA Medical Center NIH Brain and Tissue Repository/ ; //Nilüfer Ertekin-Taner/ ; //Steven Younkin/ ; //Todd Golde/ ; //Nathan Price/ ; //David Bennett, Christopher Gaiteri/ ; //Philip De Jager/ ; //Bin Zhang/ ; //Eric Schadt/ ; //Michelle Ehrlich/ ; //Vahram Haroutunian/ ; //Sam Gandy/ ; //Koichi Iijima/ ; //National Center for Geriatrics and Gerontology, Japan/ ; //Scott Noggle/ ; //Lara Mangravite/ ; },
mesh = {Humans ; *Alzheimer Disease/genetics/immunology ; Genome-Wide Association Study ; *Signal Transduction/genetics ; Age of Onset ; *Genetic Predisposition to Disease/genetics ; *Glutamic Acid/metabolism ; Male ; Female ; Quantitative Trait Loci/genetics ; Aged ; Polymorphism, Single Nucleotide/genetics ; Middle Aged ; },
abstract = {INTRODUCTION: Most genetic studies for Alzheimer's disease (AD) have been focused on late-onset AD (LOAD). There are no large genetic studies on early-onset AD (EOAD).

METHODS: We performed a multi-ancestry (non-Hispanic European, African, and East Asian) genome-wide association study (GWAS) including a total of 7,349 cases and 17,887 control. Cases with age at onset younger than 70 years were included. Sensitivity analysis including cases with onset <65 was performed. Only controls older than 70 were included to decrease the risk of developing LOAD.

RESULTS: We identified eight novel significant loci: six in the ancestry-specific analyses and two in the trans-ancestry analysis. By integrating gene-based analysis, expression quantitative trait loci (eQTL), protein quantitative trait loci (pQTL), and functional annotations, we nominate eight novel genes that are involved in microglia activation, glutamate production, and signaling pathways.

DISCUSSION: EOAD, although sharing genes with LOAD, harbors unique genes and pathways that could be used to create better prediction models or target identification.

HIGHLIGHTS: We performed the largest and first multi-ethnic genetic screening for early-onset Alzheimer's disease (AD). We identified eight novel significant loci: six in the ancestry-specific analyses and two in the trans-ancestry analysis. The novel genes are implicated microglia activation, glutamate production, and signaling pathways. EOAD, although sharing many genes with LOAD, harbors unique genes and pathways that could be used to create better prediction models or target identification for this type of AD.},
}

Humans
*Alzheimer Disease/genetics/immunology
Genome-Wide Association Study
*Signal Transduction/genetics
Age of Onset
*Genetic Predisposition to Disease/genetics
*Glutamic Acid/metabolism
Male
Female
Quantitative Trait Loci/genetics
Aged
Polymorphism, Single Nucleotide/genetics
Middle Aged

@article {pmid40556311,
year = {2025},
author = {Whitmer, RA and Baker, LD and Carrillo, MC and Snyder, HM and Cleveland, ML and Gitelman, DR and Kivipelto, M and Leng, XI and Lovato, L and Papp, KV and Pavlik, VN and Salloway, SP and Tangney, CC and Farias, ST and Williamson, JD and Wilmoth, S and Woolard, N and Yu, M and Espeland, MA and , },
title = {Baseline characteristics of the U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.S. POINTER): Successful enrollment of a diverse clinical trial cohort at risk for cognitive decline.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21},
number = {6},
pages = {e70351},
doi = {10.1002/alz.70351},
pmid = {40556311},
issn = {1552-5279},
support = {AG066910//U.S. POINTER/ ; AG062689//U.S. POINTER/ ; AG064440//U.S. POINTER/ ; AG063744//U.S. POINTER/ ; },
mesh = {Humans ; Male ; Female ; Aged ; *Cognitive Dysfunction/prevention & control ; Middle Aged ; *Life Style ; United States ; Cohort Studies ; *Risk Reduction Behavior ; Risk Factors ; },
abstract = {INTRODUCTION: The U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.S. POINTER) is a 2-year randomized controlled trial of two lifestyle interventions in 2111 older adults at increased risk for cognitive decline.

METHODS: Sociodemographic and clinical characteristics and rates of ancillary study participation were described with means and frequencies.

RESULTS: U.S. POINTER successfully enrolled a cohort, ages 60-79 years, which was ethno-racially inclusive (>30% individuals from groups often under-represented in clinical trials with cognitive outcomes) and 18% residing in neighborhoods with moderate or high levels of socioeconomic deprivation. Enrollees were cognitively intact but at increased risk for cognitive decline. Participation in ancillary studies (overall 73%) was uniformly high across sociodemographic groups.

DISCUSSION: The trial cohort meets study goals and provides a basis for assessing multidomain lifestyle intervention effects on cognitive function and other health outcomes that will generalize to large portions of the at-risk US populations.

GOV IDENTIFIER: NCT00017953.

HIGHLIGHTS: The U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.S. POINTER) enrolled individuals at enhanced risk for cognitive decline. Efforts to engage socio-demographically representative individuals were successful. Four ancillary studies with high rate of recruitment extend scientific impact.},
}

Humans
Male
Female
Aged
*Cognitive Dysfunction/prevention & control
Middle Aged
*Life Style
United States
Cohort Studies
*Risk Reduction Behavior
Risk Factors

@article {pmid40556306,
year = {2025},
author = {McVea, A and DiFilippo, A and McLachlan, M and Betcher, B and Zammit, M and Betthauser, TJ and Converse, A and Murali, D and Stone, C and Hartley, S and Johnson, S and Tudorascu, DL and Laymon, CM and Cohen, AD and Minhas, D and Luo, W and Mathis, C and Lao, PJ and Ances, B and Zaman, S and Mapstone, M and Head, E and Handen, BL and Christian, BT and , },
title = {PET-measured amyloid beta accumulates at an accelerated rate in Down syndrome compared to neurotypical populations.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21},
number = {6},
pages = {e70357},
doi = {10.1002/alz.70357},
pmid = {40556306},
issn = {1552-5279},
support = {//Eunice Kennedy Shriver National Institute of Child Health and Human Development/ ; /AG/NIA NIH HHS/United States ; },
mesh = {Humans ; *Down Syndrome/diagnostic imaging/metabolism ; *Amyloid beta-Peptides/metabolism ; Male ; Female ; *Positron-Emission Tomography ; *Alzheimer Disease/diagnostic imaging/metabolism ; Middle Aged ; *Brain/diagnostic imaging/metabolism ; Adult ; Aged ; Aniline Compounds ; Thiazoles ; },
abstract = {INTRODUCTION: Individuals with Down syndrome (DS) have a high prevalence of Alzheimer's disease (AD) and reveal an earlier age of amyloid beta (Aβ) onset compared to sporadic AD. Differences in amyloid accumulation rates between DS and sporadic AD populations have not been established.

METHODS: Participants with ≥ 3 [C-11]PiB scans (spanning > 6 years) and transitioning to Aβ+ were included, resulting in 20 DS and 23 neurotypical (NT) participants. Amyloid accumulation was compared using global standardized uptake value ratio (SUVR) for Aβ deposition, with individual growth rates (r) estimated using the logistic growth model (S U V R (t) = S U V R B L + K 1 + e - r (t - t 50) $SUVR\ (t) = SUV{{R}_
{BL}}
+ \frac{K}{
{1 + {{e}^
{ - r({t - {{t}_
{50}}
})
}}
}}
$).

RESULTS: The average growth rate in the DS cohort was 0.28 (0.08)/year versus 0.20 (0.08)/year for NT (p = . 002 $p = .002$), an increase of 40%.

DISCUSSION: Using individual longitudinal analyses, accelerated amyloid accumulation in DS is observed, This has important considerations for informing treatment trial design and monitoring beta-amyloid changes in future AD studies involving individuals with DS.

HIGHLIGHTS: Aβ accumulation rate was estimated using a logistic growth model. There was no overlap in the age of amyloid positivity between DS and NT cohorts. Participants with DS accumulate amyloid 40% faster than those with sporadic AD.},
}

Humans
*Down Syndrome/diagnostic imaging/metabolism
*Amyloid beta-Peptides/metabolism
Male
Female
*Positron-Emission Tomography
*Alzheimer Disease/diagnostic imaging/metabolism
Middle Aged
*Brain/diagnostic imaging/metabolism
Adult
Aged
Aniline Compounds
Thiazoles

@article {pmid40555893,
year = {2025},
author = {Asani, E and Hatami, H and Hamidian, G and Hatami, S},
title = {Investigating the Effects of Niosome Curcumin on the Alteration of NF-κB Gene Expression and Memory and Learning in the Prefrontal Cortex of Alzheimer's Rats.},
journal = {Molecular neurobiology},
volume = {},
number = {},
pages = {},
pmid = {40555893},
issn = {1559-1182},
abstract = {Alzheimer's disease is a neurodegenerative disorder that is the primary cause of dementia, affecting memory and learning abilities. Inflammation, oxidative stress, and the accumulation of heavy metals such as aluminum in the brain are hypothesized as key contributors to this disease. The aim of this study is to investigate the stereological changes and alterations in nuclear factor-kappa B (NF-κB) gene expression in the prefrontal cortex (PFC) of Alzheimer's male rats and the therapeutic effects of curcumin nanoparticles. Fifty-six adult male Wistar rats were divided into one of seven groups (n = 8): control, sham (ethanol), Alzheimer's disease (AD, AlCl3 at a dose of 4.2 mg/kg for 28 days), curcumin (Cur, 20 mg/kg), niosome curcumin (Niosome.Cur, 20 mg), AD + curcumin, and AD + niosome curcumin. Administration of free curcumin and niosome curcumin was carried out intraperitoneally for 14 and 7 days following the induction of Alzheimer's disease (AD). The object recognition test was performed to assess memory and learning parameters, and the T-maze test was conducted to evaluate working memory. Expression of the NF-κB inflammatory gene was detected using real-time PCR. Stereological evaluation was performed to quantitatively assess tissue damage. Results indicated that AD induction caused an increase in NF-κB gene expression, and both curcumin and niosome curcumin modulated this expression. Stereological changes revealed a quantitative increase in tissue damage in AD, and curcumin, particularly niosome curcumin, improved the disease state by modulating these parameters. Niosome curcumin enhanced memory in Alzheimer's disease. Finally, niosomes as drug-carrying nanoparticles offer a suitable option for better efficacy in a shorter time frame for antioxidants like curcumin.},
}

@article {pmid40555833,
year = {2025},
author = {Mason, HD and Latour, YL and Boughter, CT and Johnson, KR and Maric, D and Dorrier, CE and Guedes, VA and Lai, C and Duncker, PC and Johnson, AM and Manglani, M and Gill, JM and Perl, DP and Meier-Schellersheim, M and McGavern, DB},
title = {Granzyme K[+] CD8 T cells slow tauopathy progression by targeting microglia.},
journal = {Nature immunology},
volume = {},
number = {},
pages = {},
pmid = {40555833},
issn = {1529-2916},
support = {1ZIANS003111-16//U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; },
abstract = {Neurodegenerative diseases activate innate and adaptive immune responses that can either slow or accelerate disease progression. Here, we sought to define beneficial immune pressures that emerge during tauopathy development in mice and humans. Using mice that express mutant human tau in neurons, we observed that microglia slowed tauopathy development by controlling the spread of phosphorylated tau (pTau) in the central nervous system and blood. However, over time microglia converted into distressed antigen-presenting cells, acquired neuronal transcripts and were targeted by resident, clonally expanded CD8[+] T cells. These cells did not express traditional effector molecules, such as IFNγ, TNF or granzymes a/b/c, but instead deposited granzyme K (GZMK) onto microglia and were regulated by immune checkpoint proteins (TIGIT, PD-1), as blockade of TIGIT and PD-1 enhanced disease progression. GZMK[+]CD8[+] T cells also targeted microglia in pTau-rich human brain lesions resulting from age, Alzheimer's disease or chronic traumatic encephalopathy. Deletion of CD8[+] T cells in mice promoted the emergence of distressed microglia containing neuronal transcripts, markedly enhanced pTau spread and accelerated neurological decline. These data demonstrate that GZMK[+]CD8[+] T cells are a signature of tauopathy development and could potentially be harnessed to slow disease progression.},
}

@article {pmid40555736,
year = {2025},
author = {Yeasmin, S and Sharma, K and Nicolet, C and DeCristofano, L and Ataian, Y and Ranjit, A and Aghazadeh-Habashi, A and Xu, D and Schulte, M},
title = {HSV1 glycoprotein D utilizes an LY6-like binding domain to inhibit alpha7 nicotinic receptors.},
journal = {Npj viruses},
volume = {3},
number = {1},
pages = {52},
pmid = {40555736},
issn = {2948-1767},
abstract = {Herpes virus1(HSV1) is a neurotropic virus that has been linked to Alzheimer's disease. An In-silico structural homology search using α -Bgtx, identified structural homology between HSV1 gD and the nicotinic receptor neurotoxin α-Bgtx. SPR binding studies using acetylcholine binding protein from Lymnaea stagnalis, and functional two electrode voltage clamp studies of α7 nAChRs demonstrate the ability of HSV1 to interact directly with nAChRs. Molecular docking studies support the binding of a neurotoxin-like binding loop in HSV1 to a binding site similar to the neurotoxin binding domain. Interaction of HSV1 with nAChRs provides novel insights into a potential mechanism of action of HSV and its potential role in Alzheimer's disease.},
}

@article {pmid40555646,
year = {2025},
author = {Wang, Q and Sun, X and Wu, X and Liu, J and Chang, C and Liu, Y and Xu, T and Liu, Q},
title = {An Ultrasensitive Wearable Nanosensor for Minimally Invasive Self-Screening of Alzheimer's Disease.},
journal = {Nano letters},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.nanolett.5c02255},
pmid = {40555646},
issn = {1530-6992},
abstract = {The rising global prevalence of Alzheimer's disease (AD) has emerged as a critical public health challenge, placing strain on families, communities, and healthcare systems. Despite advances in diagnostic methods, current techniques for early AD detection remain limited, often being invasive, costly, and impractical for regular use. Here, we report a fully integrated wearable nanosensor offering an easily accessible and user-friendly strategy for AD screening. This biosensing platform incorporates a microneedle-based interstitial fluid (ISF) sampling device and an ultrasensitive graphene field-effect transistor (GFET) chip, enabling rapid and precise detection of AD biomarkers. Furthermore, this nanosensor was successfully validated in transgenic murine models, demonstrating reliable differentiation between AD and non-AD mouse groups with high specificity. Overall, this study offers a promising alternative tool to the existing invasive and expensive techniques for the AD preliminary screening, paving the way for drug discovery, early diagnosis, and personalized treatment of AD.},
}

@article {pmid40555627,
year = {2025},
author = {Cummings, JL and Lindle, J and Dalla, I and Zhou, Y and Zhong, K and Cheng, F},
title = {Globalization of Alzheimer's disease clinical trials: Current characteristics and future goals.},
journal = {International psychogeriatrics},
volume = {},
number = {},
pages = {100108},
doi = {10.1016/j.inpsyc.2025.100108},
pmid = {40555627},
issn = {1741-203X},
abstract = {There are 182 active trials and 138 unique drugs in the current Alzheimer's disease drug development pipeline. Of these, 33 % of trials are global involving both North American and non-North American sites. Phase 3 clinical trials are more likely to have a global distribution of sites (73 %) than Phase 1 or Phase 2 trials. Considering all global trials together, 32,284 participants are needed to populate the ongoing trials; 25,628 of these are required for Phase 3 trials. From a world region perspective, 100 % of global trials include North America, 45 % involve South America or Mexico, 71 % include Europe Western Europe or Israel, 39 % include Eastern Europe or Russia, 30 % include Asia (not including Japan), 39 % include Japan, and 43 % include South Africa, Australia, or New Zealand. A total of 46 countries are participating in current global trials. Of the 46 countries, 28 % are classified as low-and-middle-income countries. There are 5361 trial sites in active global trials; of these, 50 % are in the United States and 50 % are in other global regions. Seven percent of sites are in low-and-middle income countries. Eighty-nine percent of global trials are sponsored and funded by biopharmaceutical companies. Together these observations suggest that many global regions are involved in Alzheimer's disease clinical trials. North America has a larger number of trials and trials sites than other global regions. Low- and middle-income countries are poorly represented in terms of clinical trial sites. These regions have many patients with Alzheimer's disease and are well suited to advance trial recruitment if adequate infrastructure can be developed.},
}

@article {pmid40555521,
year = {2025},
author = {Lokesh, M and Bandaru, LJM and Rajanna, A and Dhayal, VS and Challa, S},
title = {Microglial Dysfunction Mediated by Pb and Amyloid Beta Peptides as a Possible Mechanism of Neurotoxicity.},
journal = {Journal of applied toxicology : JAT},
volume = {},
number = {},
pages = {},
doi = {10.1002/jat.4839},
pmid = {40555521},
issn = {1099-1263},
support = {58/57/2012-BMS//Indian Council of Medical Research/ ; },
abstract = {This study delves into the inflammatory and degenerative impacts of lead (Pb) toxicity and amyloid beta peptides (Aβ-peptide 1-40 and Aβ-peptide 25-35) on brain cells, particularly by fostering M1 polarization in microglial cells and subsequent neuronal cell death, crucial in conditions like Alzheimer's disease. Microglia were exposed to IC50 concentrations of Pb, and Aβ-peptide 1-40 and Aβ-peptide 25-35 exhibited notable increases in intracellular ROS levels (32.95%) upon exposure to combinatorial treatments. Moreover, there was a significant decline in total antioxidant capacity to 69.57%, suggesting oxidative damage and compromised cellular defenses against stress, coupled with heightened glutamate levels (921.3 μM). Treatment with Pb alongside Aβ-peptide 1-40 and Aβ-peptide 25-35 also led to elevated intracellular calcium levels (33.83%) and increased production of pro-inflammatory cytokines IL-6 (5.54 pg/mL), TNF-α (5.8 pg/mL), and IFN-γ (13.52 pg/mL) and reduced levels of anti-inflammatory cytokines IL-10 (5.61 pg/mL) and IL-4 (14.46 pg/mL) in microglial cells compared with the control group. Furthermore, upregulation of NF-κB/p65 pathway-associated markers was observed, and when co-cultured with neuronal cells for 24 h, polarized microglia induced neuronal cell death (57.9%). These findings provide insights into the complex molecular mechanisms involved in lead-induced neurotoxicity and neurodegenerative disorders.},
}

@article {pmid40555519,
year = {2025},
author = {Gerasimov, E and Rakovskaya, A and Pchitskaya, E and Vlasova, O and Dahl, R and Bezprozvanny, I},
title = {A positive allosteric modulator of the SERCA pump rescues hippocampal neuronal circuits dysfunction and cognitive defects in a mouse model of Alzheimer's disease.},
journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1523/JNEUROSCI.2337-24.2025},
pmid = {40555519},
issn = {1529-2401},
abstract = {Alzheimer's disease (AD) is a common neurodegenerative disorder that affects normal neuronal functioning, alters neuronal circuits activity and memory formation and storage. Disrupted neuronal calcium (Ca[2+]) signaling is one of the drivers of AD pathogenesis. Previously we suggested that positive allosteric modulators (PAMs) of the sarco/endoplasmic reticulum Ca[2+] ATPase (SERCA) pump may help to stabilize cytosolic Ca[2+] levels and exert neuroprotective effects in AD neurons. In the current manuscript we demonstrate synaptoprotective properties of several SERCA PAMs using an in vitro model of amyloid toxicity. Based on in vitro experiments, we selected the SERCA PAM NDC-9009 for in vivo evaluation in male and female 5xFAD transgenic mice model of Alzheimer's disease. Using the miniscope imaging technique, we observed hyperactivity and abnormal connectivity of hippocampal neuronal ensembles 5xFAD mice. We further discovered that the function of the hippocampal neuronal circuits in 5xFAD mice was normalized by NDC-9009 intraperitoneal administration. NDC-9009 intraperitoneal administration also rescued memory defects in 5xFAD mice as quantified by the fear conditioning behavioral test and significantly reduced accumulation of amyloid plaques in hippocampal region of these mice. The obtained results support the potential utility of NDC-9009 and other SERCA PAMs as lead molecules for development of disease-modifying treatments for AD and potentially other neurodegenerative disorders.Significance statement Alzheimer's disease (AD) is a significant medical and social burden, yet no treatment currently exists. One of the hallmarks of AD is disrupted Ca[2+] signaling, which contributes to neuronal dysfunction and degeneration. In the current study, we demonstrate the potential of the SERCA pump positive allosteric modulators (PAMs) as promising disease-modifying agents. Through an in vitro screening, we identified NDC-9009 as the most effective SERCA PAM, promoting robust cytosolic calcium clearance and exhibiting neuroprotective properties. Furthermore, using miniature fluorescence in vivo imaging, a significant restoration of hippocampal neuronal ensembles activity and cognitive function after chronic administration of NDC-9009 in the transgenic AD mouse model was demonstrated.},
}

@article {pmid40555284,
year = {2025},
author = {Park, KH and Kim, KW},
title = {Optogenetics to Biomolecular Phase Separation in Neurodegenerative Diseases.},
journal = {Molecules and cells},
volume = {},
number = {},
pages = {100247},
doi = {10.1016/j.mocell.2025.100247},
pmid = {40555284},
issn = {0219-1032},
abstract = {Neurodegenerative diseases involve toxic protein aggregation. Recent evidence suggests that biomolecular phase separation, a process in which proteins and nucleic acids form dynamic, liquid-like condensates, plays a key role in this aggregation. Optogenetics, originally developed to control neuronal activity with light, has emerged as a powerful tool to investigate phase separation in living systems. This is achieved by fusing disease-associated proteins to light-sensitive oligomerization domains, enabling researchers to induce or reverse condensate formation with precise spatial and temporal control. This review highlights how optogenetic systems such as OptoDroplet are being used to dissect the mechanisms of neurodegenerative disease. We examine how these tools have been applied in models of neurodegenerative diseases such as amyotrophic lateral sclerosis, Alzheimer's, Parkinson's, and Huntington's disease. These studies implicate small oligomeric aggregates as key drivers of toxicity and highlight new opportunities for therapeutic screening. Finally, we discuss advances in light-controlled dissolution of condensates and future directions for applying optogenetics to combat neurodegeneration. By enabling precise, dynamic control of protein phase behavior in living systems, optogenetic approaches provide a powerful framework for elucidating disease mechanisms and informing the development of targeted therapies.},
}

@article {pmid40555242,
year = {2025},
author = {Maloney, EK and Bleakley, A and White, AJ},
title = {Alzheimer's and Dementia Research Coverage in News Media Outlets Consumed by Population Groups that Are Underrepresented on Alzheimer's and Dementia-Focused Research Registries.},
journal = {Research on aging},
volume = {},
number = {},
pages = {1640275251346851},
doi = {10.1177/01640275251346851},
pmid = {40555242},
issn = {1552-7573},
abstract = {A lack of diversity in Alzheimer's (AD) and dementia research is an important barrier to identifying strategies for prevention and treatment. Research suggests media coverage of AD/dementia research will familiarize people with the issue and motivate them to place more importance in the issue in general. This study explores how news media may inform groups that are under-represented in AD/dementia through coverage of the issue. A national survey identified the media outlets that were most often consumed and used for health information within target populations. Transcripts from these media outlets were content analyzed to examine AD/dementia coverage. The timeframe included the months before and after the US FDA's approval of the drug Aduhelm and the controversy surrounding it. Results highlight differences in under-represented groups' media consumption patterns and coverage of AD/dementia and indicates a failure to inform about an event that may have widespread effect on Medicare and AD/dementia research.},
}

@article {pmid40555238,
year = {2025},
author = {Naguib, S and Lopez-Lee, C and Torres, ER and Lee, SI and Zhu, J and Zhu, D and Ye, P and Norman, K and Zhao, M and Wong, MY and Ambaw, YA and Muñoz-Castañeda, R and Wang, W and Patel, T and Bhagwat, M and Norinsky, R and Mok, SA and Walther, TC and Farese, RV and Luo, W and Sinha, SC and Wu, Z and Fan, L and Gong, S and Gan, L},
title = {The R136S mutation in the APOE3 gene confers resilience against tau pathology via inhibition of the cGAS-STING-IFN pathway.},
journal = {Immunity},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.immuni.2025.05.023},
pmid = {40555238},
issn = {1097-4180},
abstract = {The Christchurch mutation (R136S) in the APOE3 (E3S/S) gene is associated with attenuated tau load and cognitive decline despite the presence of a causal PSEN1 mutation and high amyloid burden in the carrier. However, the molecular mechanisms enabling the E3S/S mutation to mitigate tau-induced neurodegeneration remain unclear. Here, we replaced mouse Apoe with wild-type human APOE3 or APOE3S/S on a tauopathy background. The R136S mutation decreased tau load and protected against tau-induced synaptic loss, myelin loss, and reduction in hippocampal theta and gamma power. Additionally, the R136S mutation reduced interferon responses to tau pathology in both mouse and human microglia, suppressing cGAS-STING pathway activation. Treating E3 tauopathy mice with a cGAS inhibitor protected against tau-induced synaptic loss and induced transcriptomic alterations similar to the R136S mutation across brain cell types. Thus, suppression of the microglial cGAS-STING-interferon (IFN) pathway plays a central role in mediating the protective effects of R136S against tauopathy.},
}

@article {pmid40555105,
year = {2025},
author = {Zhang, Q and Zhao, H and Zhang, Z and Wei, Y and Li, N and Cui, M and Zhang, Y and Li, M and Zhang, C},
title = {Ultrasensitive photoelectrochemical biosensor of amyloid-β oligomer detection via porphyrin-based covalent organic frameworks enhanced by iron single-atom catalysts.},
journal = {Biosensors & bioelectronics},
volume = {287},
number = {},
pages = {117717},
doi = {10.1016/j.bios.2025.117717},
pmid = {40555105},
issn = {1873-4235},
abstract = {Accurate and sensitive detection of amyloid-β oligomer (AβO) is essential for understanding the development and progression of Alzheimer's disease (AD). Herein, an ultrasensitive photoelectrochemical (PEC) biosensing platform was developed by integrating photoelectrically active porphyrin-based covalent organic frameworks with Fe single-atom catalysts (Fe SACs) to enhance PEC signal. The Fe SACs demonstrate remarkable peroxidase-like activity, enabling them to oxidize 4-chloro-1-naphthol (4-CN) to generate insoluble 4-chloro-1-naphthol dimer (4-CD) precipitation on the photoelectrode surface. This process effectively reduces the PEC signal, providing a mechanism for signal amplification. the synergistic amplification effect of Fe SACs, which enhance interfacial catalytic reactions and mimic enzyme activity, the developed PEC biosensor utilizing Fe SACs enables highly sensitive and precise detection of AβO in both solution and real cerebrospinal fluid (CSF) samples with a broad linear relationship range from 10 fM to 200 nM and a low LOD of 7.4 fM. The designed novel sandwich-type PEC biosensor presents an innovative strategy for diagnosing AD at preliminary stages, while the findings also establish a foundation for the creation of advanced PEC biosensing systems that utilize p-COF-based nanomaterials integrated with multifunctional single-atom catalysts.},
}

@article {pmid40555059,
year = {2025},
author = {Faysal, M and Zehravi, M and Amin, MA and Rab, SO and Jahnavi, P and Arjun, UVNV and Gupta, JK and Billah, AAM and Vodeti, R and Prasad, PD and Aseri, SSS and Siddiqui, FA and Bin Emran, T},
title = {Clinical insights into the mechanisms of infectious microbes and microbiota in chronic neurologic and psychiatric diseases.},
journal = {Pathology, research and practice},
volume = {272},
number = {},
pages = {156090},
doi = {10.1016/j.prp.2025.156090},
pmid = {40555059},
issn = {1618-0631},
abstract = {Chronic neurologic and psychiatric diseases such as schizophrenia, depression, Parkinson's, and Alzheimer's are increasingly linked to infectious microorganisms and gut microbiota. This review explores how pathogenic microorganisms and microbial communities impact neuropsychiatric, neurodegenerative, and neuroinflammatory processes, highlighting the gut-brain axis' crucial communication network in influencing behavior and brain function. Infectious agents like bacteria, viruses, and fungi cause disease by causing neurotoxic reactions, disrupting the blood-brain barrier, and activating neuroinflammatory cascades. Gut dysbiosis impacts immunological homeostasis and neural transmission by altering the synthesis of metabolites from microorganisms, such as short-chain fatty acids and neurotransmitter precursors. Neurodegeneration and psychiatric diseases are influenced by molecular mechanisms such as toll-like receptor signaling, microglial activation, and mitochondrial dysfunction. This review highlights the potential of microbiota-targeted treatments such as probiotics, prebiotics, and microbiome transplantation as novel treatments for chronic diseases. Understanding the intricate interactions between infectious microorganisms, microbiota, and the central nervous system enables the formation of precision medicine strategies to challenge the rising incidence of neurologic and psychiatric diseases. Future research should explore causal relationships and identify specific microbial biomarkers to enhance early diagnosis, prevention, and personalized treatment plans.},
}

@article {pmid40554613,
year = {2025},
author = {Yagi-Utsumi, M and Yanaka, S and Burton-Smith, RN and Song, C and Ganser, C and Yamazaki, C and Kasahara, H and Shimazu, T and Uchihashi, T and Murata, K and Kato, K},
title = {Microgravity-Assisted Exploration of the Conformational Space of Amyloid β Affected by Tottori-Type Familial Mutation D7N.},
journal = {ACS chemical neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1021/acschemneuro.5c00217},
pmid = {40554613},
issn = {1948-7193},
abstract = {The amyloid β (Aβ) Tottori variant (D7N) exhibits unique aggregation behaviors and altered fibril formation, posing challenges for structural characterization. To overcome this, the microgravity environment on the International Space Station was employed to study Tottori-type Aβ40 fibril formation and structure. Under Earth gravity, Tottori-type Aβ40 primarily formed nonfibrillar aggregates, hindering detailed structural analysis. In contrast, microgravity significantly enhanced fibril formation and minimized amorphous aggregates. Cryo-electron microscopy revealed two structurally distinct fibril types, each comprising different protomer conformations. In both types, the N-terminal segment was disordered and nor resolved in the density maps. The D7N mutation disrupts the protection of the core by the N-terminal segment often observed in wild-type Aβ40 fibrils, enhancing the hydrophobicity-mediated aggregation propensity. However, microgravity suppressed kinetic traps and facilitated high-quality fibril formation suitable for structural studies that can explore the free energy landscape of Aβ fibril formation. These findings demonstrate the utility of microgravity for studying familial Aβ variants and potentially accelerate our understanding of Aβ aggregation mechanisms in Alzheimer's disease.},
}

@article {pmid40554602,
year = {2025},
author = {Chanda, K and Grinman, E and Clark, K and Sadhu, A and Raveendra, B and Swarnkar, S and Puthanveettil, SV},
title = {The lncRNA Gas5 is an activity-responsive scaffold that mediates cAMP-dependent synaptic plasticity.},
journal = {Science signaling},
volume = {18},
number = {892},
pages = {eadn2044},
doi = {10.1126/scisignal.adn2044},
pmid = {40554602},
issn = {1937-9145},
mesh = {Animals ; *RNA, Long Noncoding/genetics/metabolism ; *Neuronal Plasticity/genetics ; Mice ; Hippocampus/metabolism/cytology ; *Cyclic AMP/metabolism ; Receptors, Metabotropic Glutamate/metabolism/genetics ; MicroRNAs/genetics/metabolism ; Dendrites/metabolism ; Signal Transduction ; Neurons/metabolism ; Kinesins/metabolism/genetics ; Receptor, Metabotropic Glutamate 5/metabolism/genetics ; Mice, Inbred C57BL ; Mice, Knockout ; },
abstract = {Changes in the transcriptome are critical in shaping the structural plasticity of neurons, which underpins learning and long-term memory storage. Here, we explored the effect of two opposing, plasticity-associated pathways-cAMP second-messenger signaling and metabotropic glutamate receptor (mGluR1 and mGluR5) signaling-on the transcriptome in hippocampal neurons and how these pathways operate in distinct and coordinated manners to induce structural changes. Integration of transcriptome data and molecular pathway analysis identified central "hub" genes that were rapidly induced by cAMP and/or mGluR1/5 in hippocampal neurons. These included the long noncoding RNA (lncRNA) Gas5, whose expression was induced specifically by cAMP and which was targeted to dendrites by the kinesin motor protein KIF1A. In the dendrites, Gas5 interacted with various proteins and coding and noncoding RNAs associated with synaptic function and plasticity, and these interactions were altered by cAMP signaling. Gas5 interacted with the microRNA miR-26a-5p and sequestered it from several of its mRNA targets associated with neuronal function and whose translation was induced by cAMP. Gas5 was critical for excitatory synaptic transmission induced by cAMP but not those induced by mGluR1/5. Furthermore, Gas5 deficiency impaired dendritic branching and synapse morphology, and Gas5 abundance was decreased in the hippocampus of a mouse model of Alzheimer's disease. Together, these findings provide insight into the transcriptional networks involved in synaptic plasticity and a lncRNA interactome that mediates dendritically localized regulation of excitatory synaptic transmission and neuronal architecture.},
}

Animals
*RNA, Long Noncoding/genetics/metabolism
*Neuronal Plasticity/genetics
Mice
Hippocampus/metabolism/cytology
*Cyclic AMP/metabolism
Receptors, Metabotropic Glutamate/metabolism/genetics
MicroRNAs/genetics/metabolism
Dendrites/metabolism
Signal Transduction
Neurons/metabolism
Kinesins/metabolism/genetics
Receptor, Metabotropic Glutamate 5/metabolism/genetics
Mice, Inbred C57BL
Mice, Knockout

@article {pmid40554441,
year = {2025},
author = {Tu, H and Zhou, S and Lin, J},
title = {Combined Effects of Donepezil and Memantine on Behavioral and Psychological Symptoms, Cognitive Function, and Daily Living Abilities in Patients With Alzheimer's Disease.},
journal = {British journal of hospital medicine (London, England : 2005)},
volume = {86},
number = {6},
pages = {1-15},
doi = {10.12968/hmed.2024.1037},
pmid = {40554441},
issn = {1750-8460},
mesh = {Humans ; *Donepezil/administration & dosage/therapeutic use/adverse effects ; *Alzheimer Disease/drug therapy/psychology ; Male ; Female ; *Memantine/administration & dosage/therapeutic use/adverse effects ; Aged ; *Activities of Daily Living ; Retrospective Studies ; *Cognition/drug effects ; Quality of Life ; Drug Therapy, Combination ; Aged, 80 and over ; Nootropic Agents/administration & dosage ; Dose-Response Relationship, Drug ; Cholinesterase Inhibitors/administration & dosage ; },
abstract = {Aims/Background Combined with memantine, donepezil has a beneficial impact on the treatment of moderate to severe Alzheimer's disease (AD), but it can potentially increase the risk of adverse events. The aim of this study is to compare the effects of low-dose and high-dose donepezil combined with memantine on the behavioral and psychological symptoms, cognitive function, and daily living abilities of patients with moderate to severe AD, and to explore their safety. Methods This retrospective study includes 106 AD patients who received treatment in the Third People's Hospital of Fuyang from January 2022 to January 2024. The patients were grouped according to treatment regimen: patients receiving low-dose donepezil (5 mg/day) combined with memantine were included in the low-dose group (n = 45), and those receiving high-dose donepezil (10 mg/day) combined with memantine were included in the high-dose group (n = 61). The assessment results of behavioral and psychological symptoms, cognitive function, daily living ability, quality of life, sleep quality, as well as the occurrence of adverse reactions during treatment were obtained from electronic medical records for the two groups of patients before and after 24 weeks of treatment, and were compared using appropriate statistical tests. Results After 24 weeks of treatment, the scores of neuropsychiatric inventory (NPI) and behavioral pathology in Alzheimer's disease rating scale (BEHAVE-AD) were similar between the two groups (p > 0.05). The scores of Mini-Mental State Examination (MMSE) and Alzheimer's disease assessment scale-cognitive section (ADAS-Cog) were similar between the two groups (p > 0.05). The scores of activities of daily living (ADL) were comparable between the two groups (p > 0.05), and the low-dose group had significantly higher quality of life-Alzheimer's disease (QOL-AD) scores compared to the high-dose group (p < 0.05). The Pittsburgh sleep quality index (PSQI) scores of patients in the high-dose group were significantly higher than those before treatment and those in the low-dose group (p < 0.05). There was no statistically significant difference in PSQI scores between the low-dose group before and after treatment (p > 0.05). During the treatment period, the total incidence of adverse reactions in the low-dose group was significantly lower than that in the high-dose group (11.11% vs. 27.87%, p < 0.05). Conclusion Both 5 mg/day or 10 mg/day donepezil in combination with memantine holds the potential to improve behavioral and psychological symptoms, cognitive function and daily living abilities in patients with moderate-to-severe AD. In addition, high doses of donepezil may lead to decreased sleep quality in patients, increased risk of adverse reactions, and less improvement in quality of life than low doses.},
}

Humans
*Donepezil/administration & dosage/therapeutic use/adverse effects
*Alzheimer Disease/drug therapy/psychology
Male
Female
*Memantine/administration & dosage/therapeutic use/adverse effects
Aged
*Activities of Daily Living
Retrospective Studies
*Cognition/drug effects
Quality of Life
Drug Therapy, Combination
Aged, 80 and over
Nootropic Agents/administration & dosage
Dose-Response Relationship, Drug
Cholinesterase Inhibitors/administration & dosage

@article {pmid40554439,
year = {2025},
author = {Fan, Y and Wang, Z and Wu, M and Lin, L and Chen, L and Zheng, B},
title = {Bidirectional Causal Relationship Between Myopia and Neurodegenerative Diseases: Two-Sample Mendelian Randomization Analyses.},
journal = {British journal of hospital medicine (London, England : 2005)},
volume = {86},
number = {6},
pages = {1-19},
doi = {10.12968/hmed.2025.0183},
pmid = {40554439},
issn = {1750-8460},
mesh = {Humans ; Mendelian Randomization Analysis ; *Myopia/genetics/epidemiology ; Genome-Wide Association Study ; *Neurodegenerative Diseases/genetics/epidemiology ; Genetic Predisposition to Disease ; Parkinson Disease/genetics/epidemiology ; Polymorphism, Single Nucleotide ; Alzheimer Disease/genetics/epidemiology ; Amyotrophic Lateral Sclerosis/genetics/epidemiology ; },
abstract = {Aims/Background Myopia is highly prevalent in certain neurodegenerative diseases (NDDs), and both conditions demonstrate genetic susceptibility. This study investigated the potential bidirectional causal relationships between myopia and four NDDs, Parkinson's disease (PD), Alzheimer's disease (AD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS), using Mendelian randomization (MR). We aimed to determine whether myopia contributes to the risk of NDDs and vice versa. Methods We analyzed data from two independent, large-scale genome-wide association study (GWAS) cohorts on myopia, comprising 212,571 participants in the first cohort (finn-b-H7_MYOPIA) and 95,619 in the second (GCST009521). GWAS summary statistics for the four NDDs, encompassing 589,439 samples, were also incorporated. Bidirectional MR was employed to investigate causal relationships between myopia and each of the four NDDs. The inverse variance-weighted (IVW) method served as the primary analytical approach. Sensitivity analyses, including MR-Egger regression, weighted median, weighted mode, and simple mode, were conducted to assess the robustness of the findings. Horizontal pleiotropy was evaluated using the MR-Egger regression intercept test and the Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) global test, while heterogeneity was assessed via Cochran's Q test. Leave-one-out analyses were conducted to evaluate the influence of individual single nucleotide polymorphisms (SNPs). Odds ratios (ORs) with 95% confidence intervals (CIs) were reported, and statistical significance was set at p < 0.05. Results MR analyses identified no evidence of a causal relationship between myopia and refractive error and increased risk of any of the four NDDs (all p > 0.05). Similarly, none of the NDDs were associated with an increased risk of myopia or refractive error (all p > 0.05). Sensitivity analyses revealed no SNPs with significant influence on the causal associations (all p > 0.05), supporting the robustness of the findings. Conclusion This study provides no evidence of a bidirectional causal relationship between myopia and the four NDDs among individuals of European ancestry. Future research should extend beyond direct causal inference to investigate potential mediating biological mechanisms.},
}

Humans
Mendelian Randomization Analysis
*Myopia/genetics/epidemiology
Genome-Wide Association Study
*Neurodegenerative Diseases/genetics/epidemiology
Genetic Predisposition to Disease
Parkinson Disease/genetics/epidemiology
Polymorphism, Single Nucleotide
Alzheimer Disease/genetics/epidemiology
Amyotrophic Lateral Sclerosis/genetics/epidemiology

@article {pmid40554321,
year = {2025},
author = {Koff, WC and Holtzman, DM},
title = {Accelerating development of vaccines for prevention and control of Alzheimer's disease.},
journal = {Vaccine},
volume = {61},
number = {},
pages = {127410},
doi = {10.1016/j.vaccine.2025.127410},
pmid = {40554321},
issn = {1873-2518},
}

@article {pmid40554071,
year = {2025},
author = {Wang, F and Zhou, Q and Chen, Z and Xie, L and Zheng, N and Chen, Z and Sun, Q and Du, J and Lin, J and Li, B and Li, L},
title = {Cyclovirobuxine inhibits ferroptosis to mitigate Alzheimer disease in glutamate-induced SH-SY5Y cell: the role of the liquid-liquid phase separation of FTH1.},
journal = {Molecular pharmacology},
volume = {107},
number = {7},
pages = {100046},
doi = {10.1016/j.molpha.2025.100046},
pmid = {40554071},
issn = {1521-0111},
abstract = {Ferroptosis represents a distinct form of cell death that differentiates it from conventional apoptosis. Numerous studies have demonstrated that ferroptosis holds significant potential for elucidating neuronal damage in Alzheimer disease (AD). In addition, liquid-liquid phase separation has emerged as a significant biological process in recent years. It plays a crucial role in the regulation of various proteins in vivo and is closely associated with ferroptosis. Meanwhile, nuclear factor erythroid 2-related factor 2 (Nrf2) serves as a crucial signaling pathway in ferroptosis and plays a significant role in regulating many key components of the ferroptosis pathway. In addition, an increasing volume of research is being conducted on natural medicines aimed at enhancing the treatment of AD. Cyclovirobuxine (Cyc) is an alkaloid compound extracted from the traditional Chinese medicinal plant, boxwood. It has demonstrated therapeutic potential in the treatment of neurodegenerative diseases. Therefore, in this study, we established an AD cell model using glutamate-induced SH-SY5Y. In glutamate-induced SH-SY5Y cells, Cyc treatment significantly improved mitochondrial function and effectively inhibited lipid peroxidation and restored the downregulation of FTH1 levels induced. Furthermore, Cyc treatment activated the Nrf2 signaling pathway, significantly elevated the nuclear levels of Nrf2, and inhibited both iron deposition and lipid peroxidation. Cyc treatment conferred resistance to ferroptosis in erastin-stimulated SH-SY5Y cells, wherein the Nrf2 signaling pathway and FTH1 protein play crucial roles. The collective findings presented here underscore the protective mechanism of action of Cyc in AD and emphasize its potential as a therapeutic agent for AD treatment. SIGNIFICANCE STATEMENT: It reveals at the cellular level the mechanism by which cyclovirobuxine improves Alzheimer disease through the inhibition of ferroptosis, providing a novel approach and strategy for the treatment of patients with Alzheimer disease.},
}

@article {pmid40554062,
year = {2025},
author = {Ma, R and Wang, S and Cui, YL and Zhang, H and Chen, X and Xie, J and Li, Y},
title = {Therapeutic role of caveolin family in stem cell fate and development for management of chronic degenerative diseases: A scientometric study to an in-depth review.},
journal = {Journal of advanced research},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jare.2025.06.034},
pmid = {40554062},
issn = {2090-1224},
abstract = {BACKGROUND: Caveolins (CAV), a family of integral membrane proteins, are involved in regulating stem cell fate, which are critical for tissue repair and regeneration. Drawing from scientometric studies and comprehensive research, this review investigates the mechanisms by which CAV regulates stem cell fate can improve the efficiency and accuracy of stem cell therapy in treating chronic degenerative diseases (CDD). For instance, CAV1 inhibits neuronal differentiation of neural stem/progenitor cells (NSCs/NPCs) by downregulating VEGF, p44/42MAPK phosphorylation and NeuroD1 signaling pathway following ischemic stroke, while CAV3 interacts with MG53 to enhance the therapeutic effects of bone marrow mesenchymal stem cells (BMSCs) in diabetic wound healing by activating the eNOS/NO signaling pathway.

AIM OF REVIEW: Our review aims to elaborate the impact of CAV on diverse stem cell populations and regulatory mechanisms, as well as point out novel insights brought by CAV and stem cell therapy in the management of CDD, such as stroke, Alzheimer's disease (AD), Parkinson's disease (PD), diabetes, pulmonary arterial hypertension (PAH), breast cancer and liver cancer.

Based on scientometrics studies, this review synthesizes current analyses of the CAV family's role in determining the fate of various stem cell populations, thereby providing new perspectives for the prevention and treatment of CDD.},
}

@article {pmid40553999,
year = {2025},
author = {Thaler, M and Ocklenburg, S},
title = {Left-right confusion in psychiatric, neurodevelopmental and neurological disorders: a systematic review.},
journal = {Brain research bulletin},
volume = {},
number = {},
pages = {111435},
doi = {10.1016/j.brainresbull.2025.111435},
pmid = {40553999},
issn = {1873-2747},
abstract = {Left-right confusion is common in healthy individuals, but increased prevalence has been reported in several psychiatric, neurodevelopmental, and neurological disorders. The present systematic review aimed to identify disorders in which the prevalence of left-right confusion is higher than in the general population. For this purpose, a systematic review following PRISMA guidelines was conducted using the databases Google Scholar, PubMed, and Mendeley. A total of 20 quantitative case-control studies were included. Lesions in parietal brain areas and damage to temporal-parietal-occipital brain areas because of Alzheimer's disease were associated with severe impairments in left-right orientation. Furthermore, evidence for developmental impairments in direction assignment was provided by studies on developmental topographical disorientation (DTD). These DTD-related impairments are associated with low functional connectivity between the hippocampus and the right prefrontal cortex. Individuals with DTD show significantly poorer performance in direction discrimination compared to healthy subjects. In addition, the review highlights that, despite previous research, there remains a substantial need for further studies and for the development of a uniform definition and operationalization of left-right confusion in clinical populations.},
}

@article {pmid40553978,
year = {2025},
author = {Al-Kuraishy, HM and Al-Maiahy, TJ and Sulaiman, GM and Mohammed, HA and Albuhadily, AK and Al-Gareeb, AI and Abomughaid, MM},
title = {The potential role of aryl hydrocarbon receptor in Alzheimer's disease: Protective or detrimental.},
journal = {Ageing research reviews},
volume = {},
number = {},
pages = {102810},
doi = {10.1016/j.arr.2025.102810},
pmid = {40553978},
issn = {1872-9649},
abstract = {Alzheimer's disease (AD) is the main cause of dementia in the old-age population worldwide. AD is a progressive brain neurodegenerative disease due to genetic and environmental factors that induce the accumulation of intracellular hyperphosphorylated tau protein and extracellular amyloid protein (Aβ). Particularly, cholinergic neurons in the prefrontal cortex and hippocampus are mainly affected in AD, resulting in cognitive impairment and memory dysfunction. Therefore, restoration of cholinergic neurotransmission by cholinergic agonists such as tacrine and donepezil could be effective in the management of AD. However, anti-AD medications cannot reverse the fundamental AD neuropathology. Therefore, targeting other pathways might be reasonable in the management of AD. Interestingly, aryl hydrocarbon receptors (AHRs), which are sensors for xenobiotics and enterobiotics, are involved in age-related neurodegeneration. It has been shown that AHRs have detrimental effects on AD neuropathology by disruption of BBB integrity and induction of cognitive impairment. Conversely, activation of brain AHRs by tryptophan attenuates the inflammatory reactions in AD. These findings emphasized the controversial roles of AHRs in the pathogenesis of AD. Therefore, this review discusses the exact role of AHRs in AD regarding the molecular mechanisms and related signaling pathways.},
}

@article {pmid40553977,
year = {2025},
author = {Jiang, H and Qi, H and Tang, A and Hu, S and Lai, J},
title = {Start the Engine of Neuroregeneration: A Mechanistic and Strategic Overview of Direct Astrocyte-to-Neuron Reprogramming.},
journal = {Ageing research reviews},
volume = {},
number = {},
pages = {102808},
doi = {10.1016/j.arr.2025.102808},
pmid = {40553977},
issn = {1872-9649},
abstract = {The decline of adult neurogenesis and neuronal function during aging underlies the onset and progression of neurodegenerative diseases such as Alzheimer's disease. Conventional therapies, including neurotransmitter modulators and antibodies targeting pathogenic proteins, offer only symptomatic improvement. As the most abundant glial cells in the brain, astrocytes outnumber neurons nearly fivefold. However, their proliferative and transdifferentiation potential renders them ideal candidates for in situ neuronal replacement. Direct astrocyte-to-neuron reprogramming offers a promising regenerative approach to restore damaged neural circuits. Herein, we propose a "car start-up" model to conceptualize this process, emphasizing the need to inhibit non-neuronal fate pathways (release the handbrake), suppress transcriptional repressors (release the footbrake), and activate neuron-specific gene expression (step on the gas). Additionally, overcoming metabolic barriers in the cytoplasm is essential for successful lineage conversion. Viral or non-viral vectors deliver reprogramming factors, while small molecules serve as metabolic and epigenetic fuel to boost efficiency. In summary, we review the current evidence supporting direct astrocyte-to-neuron reprogramming as a viable regenerative strategy in the aging brain. We also highlight the conceptual "car start-up" model as a useful framework to dissect the molecular logic of lineage conversion and emphasize its promising therapeutic potential for combating neurodegenerative diseases.},
}

@article {pmid40553976,
year = {2025},
author = {da Silva, SP and Lampraki, C and Dos Santos Rêgo, T and Ghisletta, P and Kliegel, M and Maurer, J and Studer, M and Gouveia, ÉR and de Maio Nascimento, M and Ihle, A},
title = {Can Cognitive Reserve Offset APOE-Related Alzheimer's Risk? A Systematic Review.},
journal = {Ageing research reviews},
volume = {},
number = {},
pages = {102809},
doi = {10.1016/j.arr.2025.102809},
pmid = {40553976},
issn = {1872-9649},
abstract = {Alzheimer's disease (AD) is a neurocognitive disorder that affects a significant part of the population. Its symptoms include progressive loss of memory and executive dysfunction. Genetic susceptibility to AD can be influenced by allele variants of the APOE gene. On the other hand, lifelong experiences such as educational attainment, occupational complexity, and leisure activities, known proxies for cognitive reserve (CR), may modulate gene expression, ultimately impacting AD susceptibility. In this study, we systematically investigated research that explored the interaction between APOE-related AD outcomes and CR. The literature search was conducted using PubMed and all Web of Science databases. We screened 33,861 references, of which 15 met the inclusion criteria. The studies varied in research design, population characteristics, proxies for CR, and measured outcomes. The publications presented mixed results, with some indicating protective effects (n = 7), others showing detrimental effects (n = 4), and still others suggesting no significant interaction effects (n = 4). Some of these findings may be attributed to the reliance on individual proxies, which may capture only limited aspects or different dimensions of the broader CR framework. Overall, our analysis suggests that individual risk factors may interact in complex ways and that even genetic predispositions can potentially be influenced by CR. Implications for CR and aging research as well as public health policies are discussed.},
}

@article {pmid40553915,
year = {2025},
author = {Jouryabi, YR and Lashgari, R and Ardekani, BA and , },
title = {A comparative study of rigid-body registration algorithms for the alignment of longitudinal structural MRI of the brain.},
journal = {Journal of neuroscience methods},
volume = {},
number = {},
pages = {110517},
doi = {10.1016/j.jneumeth.2025.110517},
pmid = {40553915},
issn = {1872-678X},
abstract = {BACKGROUND: Longitudinal structural MRI (sMRI) may be used to characterize brain morphological changes over time. A key requirement is accurate rigid-body alignment of longitudinal sMRI.

NEW METHOD: We have developed the automatic temporal registration algorithm (ATRA) for this purpose. ATRA is a landmark-based approach capable of registering dozens sMRI simultaneously.

The aim of this research was to evaluate the accuracy and inverse-consistency of ATRA in comparison to FSL, FreeSurfer, and ANTS. Absent a ground truth, it is only possible to determine the degree of discrepancy between algorithms. We propose that if the discrepancy exceeds a certain threshold, the relative accuracy of algorithms could be determined visually. We computed the discrepancy between ATRA and each of the other three methods for the alignment of 150 pairs of longitudinal sMRI.

RESULTS: We visually rated the accuracy of alignments in cases where the discrepancy was greater than.5mm while the rater was agnostic to the registration method. In those instances, ATRA was considered more accurate than FSL in 46 out of 48 cases (p<.0001), more accurate than FreeSurfer in 6 out of 7 cases (p=.0625), and more accurate than ANTS in all 6 cases (p<.05). ATRA was also significantly more inverse-consistent than all other methods. FreeSurfer was more inverse-consistent than FSL and ANTS, while ANTS outperformed FSL (p<.0001 for all 6 pairwise comparisons).

CONCLUSIONS: In addition to being capable of performing unbiased group-wise registration, ATRA is the most accurate algorithm in comparison to several commonly used rigid-body alignment methods.},
}

@article {pmid40553887,
year = {2025},
author = {Huang, ZL and Qu, EK and Yang, LR and Luo, R and Liang, YN and Liu, SJ and Xu, YZ and Zhang, DB},
title = {Frititaipaines A-O, undescribed cevanine-type isosteroidal alkaloids from the bulbs of Fritillaria taipaiensis and their anti-neuroinflammatory and AChE inhibitory activities.},
journal = {Phytochemistry},
volume = {},
number = {},
pages = {114582},
doi = {10.1016/j.phytochem.2025.114582},
pmid = {40553887},
issn = {1873-3700},
abstract = {Fifteen undescribed cevanine-type isosteroidal alkaloids, frititaipaines A-O (1-15), and twelve known analogs (16-27) were isolated from the bulbs of Fritillaria taipaiensis. The structures of the previously undescribed compounds, including their absolute configurations, were fully elucidated based on spectroscopic, electronic circular dichroism spectra, and single-crystal X-ray diffraction data analysis. Compounds 3, 5, and 6 displayed significant inhibitory effects against lipopolysaccharide induced NO release in BV-2 microglial cells with IC50 values of 6.3, 10.7, and 6.7 μM, respectively. All compounds showed no or weak acetylcholinesterase inhibitory activities as determined by the Ellman's method. Network pharmacological analysis and molecular docking results suggest that 3 may be able to treat Alzheimer's disease through pathways in cancer, PI3K-Akt signaling pathway, Rap1 signaling pathway, etc., as well as by binding PIK3CA, AKT1, SRC, PIK3R1, and ITGB1 targets.},
}

@article {pmid40553615,
year = {2025},
author = {Theodorou, A and Melanis, K and Athanasaki, A and Palaiodimou, L and Stefanou, MI and Tsalouchidou, PE and Vassilopoulos, E and Kouzoupis, A and Themistocleous, M and Paraskevas, GP and Tsivgoulis, G and Tzavellas, E},
title = {Cerebral amyloid angiopathy and amyloid load distribution detected on amyloid-positron emission tomography: A systematic review and meta-analysis.},
journal = {European stroke journal},
volume = {},
number = {},
pages = {23969873251349657},
doi = {10.1177/23969873251349657},
pmid = {40553615},
issn = {2396-9881},
abstract = {INTRODUCTION: There are limited data regarding the amyloid positron emission tomography (PET) imaging among patients with Cerebral Amyloid Angiopathy (CAA). We sought to assess the amyloid load distribution detected on amyloid-PET among CAA patients compared to patients with Alzheimer's Disease (AD), patients with hypertension (HTN) related hemorrhage (ICH) and healthy controls (HC).

PATIENTS AND METHODS: A systematic review and meta-analysis of published studies with available data on global and regional amyloid-PET uptake was conducted. Comparisons with respect to amyloid load distribution were investigated using random-effects models based on the ratio of mean (RoM) amyloid-PET uptake. RoM < 1 and RoM > 1 indicate lower and higher global or regional amyloid-PET uptake in CAA compared to another population, respectively.

RESULTS: We identified 16 cohorts, comprising 271 CAA patients (mean age: 72 years; women: 46%) versus 130 AD patients (mean age: 73 years; women: 44%), 180 patients with HTN-related ICH (mean age: 66 years; women: 36%) and 61 HC (mean age: 71 years; women: 46%) with available data on amyloid-PET. Global amyloid PET ratio differentiated CAA from AD [RoM: 0.93; 95% CI: 0.90-0.96; p < 0.0001], HTN-related ICH [RoM: 1.25; 95% CI: 1.20-1.31; p < 0.0001], and HC [RoM: 1.26; 95% CI: 1.23-1.29; p < 0.0001]. Occipital amyloid-PET uptake [RoM: 1.20; 95% CI: 1.15-1.26; p < 0.0001] was higher in CAA compared to HTN-related ICH, and Occipital-to-global [RoM: 1.05; 95% CI: 1.03-1.07; p < 0.0001] ratio of amyloid-PET uptake differentiated also CAA from AD.

CONCLUSIONS: CAA is characterized by a distinct amyloid-PET burden and distribution compared to AD patients, patients with HTN-related ICH and HC. These findings may contribute to the design and conduct of future randomized controlled clinical trials, aiming to treat CAA at preclinical stages.},
}

@article {pmid40553395,
year = {2025},
author = {Xu, Z and Zhu, Y and Liu, L and Liu, C and Zhang, Z and Li, M and Yao, L and Wang, F and Dong, Z and Gao, S and Kang, L and Shi, L},
title = {An analysis of the therapeutic efficacy and underlying mechanisms of combining lycopene with dental pulp stem cells to ameliorate alzheimer's disease in rats.},
journal = {Metabolic brain disease},
volume = {40},
number = {6},
pages = {233},
pmid = {40553395},
issn = {1573-7365},
}

@article {pmid40553385,
year = {2025},
author = {Giffard, J and Li, R and Roccati, E and Vogel, AP and Bindoff, AD and Goldberg, LR and Bai, Q and Alty, J},
title = {Rapid repetitive syllable sounds associate with episodic memory, executive function, and working memory in cognitively healthy and subjectively impaired older adults.},
journal = {GeroScience},
volume = {},
number = {},
pages = {},
pmid = {40553385},
issn = {2509-2723},
support = {2004051//National Health and Medical Research Council/ ; MRFF1170820//Department of Health and Aged Care, Australian Government/ ; FT220100253//Australian Research Council/ ; Research Training Program (RTP) Scholarship//Department of Education, Australian Government/ ; },
abstract = {Non-invasive screening tools for Alzheimer's disease (AD) risk are needed. Decline in episodic memory and subjective cognitive impairment (SCI) are both associated with elevated AD risk. We investigated associations between three cognitive domains (episodic memory, executive function, and working memory) and motor speech performance in older adults with healthy cognition (HC) or SCI. In total, 1014 community-dwelling participants (cross-sectional sample: 843 HC, mean 66.9 years, 72.8% female; 171 SCI, mean 66.3 years, 70.8% female) remotely completed cognitive tests (Paired Associates Learning and Spatial Working Memory from the Cambridge Neuropsychological Test Automated Battery) and motor speech tests (Tasmanian [TAS] Test). We evaluated whether acoustic motor speech features extracted from 10-s tests of "pa," "ta," or "ka" syllable repetition improved episodic memory, executive function, and working memory regression models over age, sex, education, anxiety, and depression (ΔAIC > 2). Motor speech features improved estimation of cognitive scores over fixed demographic and clinical variables in each group and cognitive domain. In summary, we found associations between motor speech performance and cognition in older adults. Short motor speech tests demonstrate potential for non-invasive, cost-effective AD risk screening. Longitudinal research is needed to investigate relationships between individual motor speech features and cognitive changes confirmed to result from the progression of AD.},
}

@article {pmid40553339,
year = {2025},
author = {Pandey, S and Choudhari, JK and Tripathi, A and Singh, A and Antony, A and Chouhan, U},
title = {Artificial Intelligence-Based Genome Editing in CRISPR/Cas9.},
journal = {Methods in molecular biology (Clifton, N.J.)},
volume = {2952},
number = {},
pages = {273-282},
pmid = {40553339},
issn = {1940-6029},
mesh = {*Gene Editing/methods ; *CRISPR-Cas Systems ; *Artificial Intelligence ; Humans ; RNA, Guide, CRISPR-Cas Systems/genetics ; Precision Medicine ; Genomics/methods ; },
abstract = {Artificial intelligence (AI) plays a critical role in predicting and improving genome editing methods, including CRISPR/Cas9. Recently, several AI models, such as DeepCRISPR, CRISTA, and Deep High Fidelity (DeepHF), have been utilized to design guide RNAs (gRNAs) for CRISPR-Cas systems. These models assess genomic context, desired mutation type, on-target and off-target scores, and potential off-target locations. AI models help improve various genome editing methods, such as base, prime, and epigenome editing, which allow for precise and intentional changes to DNA sequences without the need for donor DNA templates. Furthermore, integrating AI with genome editing and precision medicine enables the creation of personalized treatments tailored to each individual's unique genetic profile. Examining genomic data enables the identification of mutations, variations, and biomarkers linked to diseases like cancer, diabetes, and Alzheimer's disease. Integrating AI with genome editing can potentially enhance genetic modification techniques' precision, efficiency, and cost-effectiveness. Furthermore, it presents novel prospects for fields like genetics, biomedicine, and healthcare, which could significantly impact human health. However, several challenges still exist, including high costs, inaccurate edits, and effective delivery methods for CRISPR components, improved editing performance, and safety in clinical applications.},
}

*Gene Editing/methods
*CRISPR-Cas Systems
*Artificial Intelligence
Humans
RNA, Guide, CRISPR-Cas Systems/genetics
Precision Medicine
Genomics/methods

@article {pmid40553235,
year = {2025},
author = {Bobkova, NV and Chuvakova, LN and Kononova, SV and Kovalev, VI and Sukhikh, GT and Zatsepina, OG and Rezvykh, AP and Evgen'ev, MB},
title = {Similar Normalizing Effect of HSP70 and YB-1 Stress Proteins on the Brain Transcription of a Mouse Model of Alzheimer's Disease.},
journal = {Molecular neurobiology},
volume = {},
number = {},
pages = {},
pmid = {40553235},
issn = {1559-1182},
support = {24-25-00465//The Russian Science Foundation/ ; 24-25-00465//The Russian Science Foundation/ ; 24-14-00216//The Russian Science Foundation/ ; 24-14-00216//The Russian Science Foundation/ ; },
abstract = {Previously, we demonstrated the therapeutic effects of intranasal administration of human HSP70 and YB-1 proteins in various models of AD, including olfactory bulbectomized (OBX) mice. Herein, we investigated the effect of these two stress proteins on transcription in the hippocampus and cortex of OBX mice. Despite different structures, both proteins frequently caused pronounced normalizing changes in the transcription of the same genes. Thus, the genes that normalized their expression due to the action of recHSP70 or recYB-1 coincide by 61%. More than 60% of these common target genes exhibited complete restoration to a pattern similar to that of the control sham-operated mice. Notably, the number of genes with altered expression after administration of the proteins was twice as high in the hippocampus as in the cortex. In the brain of OBX mice, the protein application led to a normalization of the expression of many genes related to AD pathogenesis, including genes that participated in the metabolism of Aβ and tau proteins. Importantly, the normalized genes also include loci involved in ribosome biogenesis, as well as genes responsible for neurotransmitter transport, cognition, apoptosis, mitochondrial functions, and protection from oxidative stress. A significant positive effect of both proteins was demonstrated in all six cell types studied in the brain of OBX mice, with the most pronounced effect observed in the astrocytes. Besides AD-related genes, both proteins normalized the expression of several genes implicated in the development of major depression and other neurodegenerative diseases.},
}

@article {pmid40553197,
year = {2025},
author = {Unal, O and Akgun-Unal, N and Baltaci, AK},
title = {Unveiling mysteries of aging: the potential of melatonin in preventing neurodegenerative diseases in older adults.},
journal = {Biogerontology},
volume = {26},
number = {4},
pages = {125},
pmid = {40553197},
issn = {1573-6768},
mesh = {Humans ; *Melatonin/therapeutic use ; *Neurodegenerative Diseases/prevention & control/metabolism ; *Aging/drug effects/metabolism ; Aged ; Antioxidants/therapeutic use ; Animals ; Oxidative Stress/drug effects ; *Neuroprotective Agents/therapeutic use ; },
abstract = {Neurodegenerative conditions, including Alzheimer's disease, Parkinson's disease, and Huntington's disease, result in a substantial health problem for the elderly, marked by ongoing neuronal degeneration and a deterioration in mental faculties. These disorders are frequently linked to oxidative stress, problems with mitochondria, and persistent inflammation in the brain, which worsen neuronal damage. The neurohormone melatonin, primarily secreted by the pineal gland, has gained recognition as a promising therapeutic agent due to its antioxidant, anti-inflammatory, and neuroprotective effects. Melatonin's functions extend beyond its regulation of circadian rhythms, as research has demonstrated its ability to remove free radicals, improve mitochondrial performance, and adjust immune system responses, ultimately reducing the progression of neurodegenerative disease. Research findings from preclinical and clinical trials imply that taking melatonin supplements could lead to improved cognitive abilities, slower disease progression, and an overall better quality of life for elderly individuals suffering from neurodegenerative conditions. The mechanisms through which melatonin acts, the best dosage, and its long-term effectiveness are still being researched. This review underscores the potential benefits of melatonin as a supplementary treatment for neurodegenerative disorders in older adults, stressing the necessity for additional studies to confirm its efficacy and standardize its use in treatment plans.},
}

Humans
*Melatonin/therapeutic use
*Neurodegenerative Diseases/prevention & control/metabolism
*Aging/drug effects/metabolism
Aged
Antioxidants/therapeutic use
Animals
Oxidative Stress/drug effects
*Neuroprotective Agents/therapeutic use

@article {pmid40553116,
year = {2025},
author = {Murrell, E and Narciso, L and Desmond, KL and Chow, C and Lindberg, A and Garcia, A and Mathis, CA and Svensson, S and Strafella, AP and Vasdev, N},
title = {First-in-human PET neuroimaging of [[18]F]OXD-2314.},
journal = {European journal of nuclear medicine and molecular imaging},
volume = {},
number = {},
pages = {},
pmid = {40553116},
issn = {1619-7089},
support = {Tau Consortium//Tau Consortium/ ; CurePSP//CurePSP/ ; MJFF-024347 & MJFF-024348//Michael J. Fox Foundation for Parkinson's Research/ ; Tier-1//Canada Research Chairs/ ; JELF//Ontario Research Foundation/ ; JELF//Canada Foundation for Innovation/ ; Rossy Foundation//Rossy Foundation/ ; Krembil Foundation//Krembil Foundation/ ; Azrieli Foundation//Azrieli Foundation/ ; PJT-173540/CAPMC/CIHR/Canada ; },
abstract = {PURPOSE: This first-in-human positron emission tomography (PET) study evaluates [[18]F]OXD-2314, a radiopharmaceutical designed for imaging tau in non-Alzheimer's disease tauopathies.

METHODS: Synthesis of [[18]F]OXD-2314 was automated using a commercial module and validated for human use. Dynamic PET imaging was performed in healthy control subjects (2 female, 2 male, ages 49-65 years). Kinetic modelling was performed from brain time-activity curves and radiometabolite-corrected arterial input functions to estimate total distribution volumes (VT) in each region of interest.

RESULTS: [[18]F]OXD-2314 met all release criteria for human use. PET imaging revealed an initial whole brain peak of 2.3 standardized uptake value, followed by a steady washout. Distribution of radioactivity was uniform among brain regions (VT range: 2.21 ± 0.29 to 2.81 ± 0.43 mL/cm[3]).

CONCLUSIONS: [[18]F]OXD-2314 was successfully translated to first-in-human PET imaging. No adverse events were reported and PET imaging in patient populations of non-AD tauopathies is underway.},
}

@article {pmid40552996,
year = {2025},
author = {Wang, T and Yan, S and Shan, Y and Xue, H and Xing, Y and Bi, S and Chen, Z and Xi, H and Qi, Z and Tang, Y and Lu, J},
title = {Modulation of Cortical and Hippocampal Functional MRI Connectivity Following Transcranial Alternating Current Stimulation in Mild Alzheimer Disease.},
journal = {Radiology},
volume = {315},
number = {3},
pages = {e241463},
doi = {10.1148/radiol.241463},
pmid = {40552996},
issn = {1527-1315},
mesh = {Humans ; *Alzheimer Disease/therapy/physiopathology/diagnostic imaging ; Female ; *Magnetic Resonance Imaging/methods ; Male ; *Hippocampus/diagnostic imaging/physiopathology ; Aged ; *Transcranial Direct Current Stimulation/methods ; Prospective Studies ; Middle Aged ; *Cerebral Cortex/diagnostic imaging/physiopathology ; Treatment Outcome ; },
abstract = {Background Transcranial alternating current stimulation (tACS) may be effective for improving cognitive function in Alzheimer disease (AD), but its impact on brain functional connectivity (FC) has not been well studied. Purpose To evaluate tACS efficacy in improving cognitive performance and modulating FC between brain regions in individuals with AD using functional MRI. Materials and Methods In this prospective randomized controlled trial (September 2020 to April 2022), participants with mild AD were assigned to active (40 Hz tACS with 15-mA intensity) or sham (no γ frequency or current) tACS groups for 3 weeks (referred to as week 3), with a 3-month follow-up (referred to as month 3). Functional MRI and cognitive testing were performed at baseline, week 3, and month 3. Primary outcomes were changes in Mini-Mental State Examination and Montreal Cognitive Assessment scores from baseline to week 3. Secondary outcomes included FC changes within multiple cortical networks and between cortex and hippocampus from baseline to week 3 and month 3, assessed using Fisher z-transformed correlation coefficient (hereafter, z score). Results Forty-six participants were randomized into the active group (n = 23; median age, 66 years; IQR, 62-69 years; 16 female participants) or the sham group (n = 23; mean age, 64 years; IQR, 61-69 years; 14 female participants). The active group had higher Mini-Mental State Examination (median score change, 2 [IQR, 1-5] vs 0 [IQR, -1 to 2]; P = .001) and Montreal Cognitive Assessment (median score change, 2 [IQR, 0-4] vs 0 [IQR, -1 to 2]; P = .03) scores than the sham group at week 3, respectively. Compared with the sham group, the active group had increased FC between left hippocampus and left middle cingulate gyrus (z score difference, 0.29; 95% CI: 0.17, 0.42; false discovery rate [FDR]-adjusted P < .001) and between the left hippocampus and the left middle frontal gyrus (z score difference, 0.16; 95% CI: 0.03, 0.29; FDR-adjusted P = .04) within the posterior default-mode network (z score difference, 0.40; 95% CI: 0.07, 0.73; FDR-adjusted P = .046) and within the visual network (z score difference, 0.45; 95% CI: 0.17, 0.73; FDR-adjusted P = .007) from baseline to week 3. Conclusion Cognitive performance in mild AD improved following tACS, with increased FC within cortical networks and between the hippocampus and specific cortical regions. ClinicalTrials.gov Identifier: NCT03920826 © RSNA, 2025 Supplemental material is available for this article. See also the editorial by Shepherd in this issue.},
}

Humans
*Alzheimer Disease/therapy/physiopathology/diagnostic imaging
Female
*Magnetic Resonance Imaging/methods
Male
*Hippocampus/diagnostic imaging/physiopathology
Aged
*Transcranial Direct Current Stimulation/methods
Prospective Studies
Middle Aged
*Cerebral Cortex/diagnostic imaging/physiopathology
Treatment Outcome

@article {pmid40552995,
year = {2025},
author = {Shepherd, TM},
title = {Imaging the Treatment of Alzheimer Disease: 2030 Could Look Very Different.},
journal = {Radiology},
volume = {315},
number = {3},
pages = {e251704},
doi = {10.1148/radiol.251704},
pmid = {40552995},
issn = {1527-1315},
mesh = {Humans ; *Alzheimer Disease/diagnostic imaging/therapy ; Brain/diagnostic imaging ; *Diagnostic Imaging ; },
abstract = {"Just Accepted" papers have undergone full peer review and have been accepted for publication in Radiology. This article will undergo copyediting, layout, and proof review before it is published in its final version. Please note that during production of the final copyedited article, errors may be discovered which could affect the content.},
}

Humans
*Alzheimer Disease/diagnostic imaging/therapy
Brain/diagnostic imaging
*Diagnostic Imaging

@article {pmid40552864,
year = {2025},
author = {Chung, D and Noh, Y and Yu, YM and Ah, YM},
title = {The Association between Tumor Necrosis Factor-Alpha Inhibitor Use and Dementia Risk in Patients with Rheumatoid Arthritis: A Systematic Review and Meta-Analysis.},
journal = {Gerontology},
volume = {71},
number = {4},
pages = {308-318},
doi = {10.1159/000544123},
pmid = {40552864},
issn = {1423-0003},
mesh = {Humans ; *Arthritis, Rheumatoid/drug therapy ; *Dementia/epidemiology/chemically induced ; *Tumor Necrosis Factor-alpha/antagonists & inhibitors ; *Antirheumatic Agents/therapeutic use/adverse effects ; Risk Factors ; Observational Studies as Topic ; *Tumor Necrosis Factor Inhibitors/therapeutic use/adverse effects ; Aged ; },
abstract = {INTRODUCTION: Tumor necrosis factor-alpha inhibitors (TNFi), commonly prescribed for rheumatoid arthritis (RA), have been studied for their potential association with dementia risk. However, previous findings are inconclusive. This study aimed to evaluate the impact of TNFi use on dementia in patients with RA.

METHODS: A systematical search of MEDLINE, Embase, and CENTRAL databases from inception to October 1, 2023, was conducted. Longitudinal comparative studies investigating the association between TNFi use and risk of dementia in patients with RA were included. Pooled adjusted risks of dementia and meta-analysis were conducted to synthesize relative estimates with 95% confidence intervals (CIs).

RESULTS: Seven observational studies involving 633,089 patients with RA were included, of which 6 were included in the meta-analysis. The pooled meta-analysis comparing the risk of dementia (hazard ratio [HR] = 0.77, 95% CI: 0.64-0.93) and Alzheimer's disease (AD) (odds ratio = 0.31, 95% CI: 0.23-0.43) between TNFi users and non-users showed a significant association. However, the pooled HR for AD risk was inconsistent. Also, the subgroup analyses indicated that TNFi use was associated with a decreased dementia risk in older adult patients with a mean age of ≥65 years at enrollment (HR = 0.86, 95% CI: 0.80-0.92) and TNFi new users (HR = 0.86, 95% CI: 0.80-0.92).

CONCLUSIONS: Systematic review and meta-analysis suggest that lowering the level of systemic TNF-alpha by using TNFi could lower the risk of dementia. However, given the retrospective nature of the included studies, further prospective studies are needed to evaluate the role of TNFi in dementia onset.},
}

Humans
*Arthritis, Rheumatoid/drug therapy
*Dementia/epidemiology/chemically induced
*Tumor Necrosis Factor-alpha/antagonists & inhibitors
*Antirheumatic Agents/therapeutic use/adverse effects
Risk Factors
Observational Studies as Topic
*Tumor Necrosis Factor Inhibitors/therapeutic use/adverse effects
Aged

@article {pmid40552726,
year = {2025},
author = {Cha, YJ and Kim, YK and Lim, YJ and Kim, CH and Park, SE and Kang, YP and Shin, MK},
title = {Lipidomic Network Analysis Reveals Amyloid-β-Induced Lysosomal Lipid Accumulation in the Cortex and Hippocampus of 5xFAD Mice.},
journal = {Journal of proteome research},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.jproteome.4c01133},
pmid = {40552726},
issn = {1535-3907},
abstract = {The 5xFAD mouse model serves as a valuable experimental system for investigating Alzheimer's disease (AD), specifically amyloid-beta (Aβ)-induced AD pathology. In this study, we explored temporal, regional, and sex-specific alternations in the lipidome within the cortex and hippocampus of 5xFAD mice. Our results revealed that lipid alternations become more pronounced with the progression of Aβ pathology in the cerebral cortex and hippocampus. These lipid changes were also more significant in the female mice, which exhibited more severe Aβ pathology than male mice. Through lipid network analysis, we identified AD-specific lipid coexpression network modules in both brain regions, marked by enriched lysosomal lipids such as BMP and GM3. Notably, this lipid profile was also observed in microglia cells overexpressing the Swedish mutant form of Aβ precursor protein (APPswe). Given the critical role of BMP in lysosomal lipid and membrane degradation, and the observed enhancement of GM3 accumulation under lysosomal inhibition in APPswe-transfected microglial cells, these findings suggest that Aβ-mediated microglial lysosomal dysfunction may contribute to AD progression. Overall, we discovered a previously unrecognized role of Aβ in dysregulating lysosomal lipid metabolism and highlighted the utility of lipidomics and network analysis as complementary approaches for elucidating disease mechanisms.},
}

@article {pmid40552722,
year = {2025},
author = {Weaver, DF},
title = {Alzheimer's Is Not a Single Disease.},
journal = {ACS chemical neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1021/acschemneuro.5c00446},
pmid = {40552722},
issn = {1948-7193},
}

@article {pmid40552713,
year = {2025},
author = {K, R and Ma, Y and Bhat, M and Kumar, K and Pai K, K},
title = {Exploring the perceptual and cognitive deficits in older individuals and individuals with Alzheimer's disease using the dichotic double-word test- Kannada (DDWT-K).},
journal = {Neuropsychology, development, and cognition. Section B, Aging, neuropsychology and cognition},
volume = {},
number = {},
pages = {1-17},
doi = {10.1080/13825585.2025.2519465},
pmid = {40552713},
issn = {1744-4128},
abstract = {Dichotic Listening (DL) is a test where auditory stimuli are presented simultaneously to each ear. There are limited systematic dichotic studies that have compared the differences between normal aging and Alzheimer's disease (AD). Hence the study aimed to explore the perceptual and cognitive deficits in normal aging and Alzheimer's disease using the developed novel test. The developed novel dichotic test was administered on a total of 65 subjects, 25 middle-aged adults 25 older adults, and 15 older adults with Alzheimer's disease under four conditions. The within-subject comparison revealed a significant left ear (LE) deficit in older adults and Alzheimer's subjects. The results showed a significantly poorer score in switch attention when compared to forced attention only in Alzheimer's subjects. Overall, the study was able to identify significant perceptual and cognitive deficits in older individuals and individuals with Alzheimer's population. Moreover, the switch attention condition showed a significant reduction in the performance of Alzheimer's patients when compared to older individuals, thus being a remarkable distinguishing factor in the differential diagnosis of cognitive deficits between the two.},
}

@article {pmid40552707,
year = {2025},
author = {Siriwardhana, C and Gunaratnam, B and Kulasekera, KB},
title = {Personalized Treatment Selection for Multivariate Ordinal Scale Outcomes and Multiple Treatments.},
journal = {Pharmaceutical statistics},
volume = {24},
number = {4},
pages = {e70023},
doi = {10.1002/pst.70023},
pmid = {40552707},
issn = {1539-1612},
support = {R03AG075034/AG/NIA NIH HHS/United States ; 2U54MD007601-36/MD/NIMHD NIH HHS/United States ; },
mesh = {Humans ; *Precision Medicine/methods/statistics & numerical data ; Alzheimer Disease/drug therapy ; Treatment Outcome ; Computer Simulation ; Models, Statistical ; Clinical Trials as Topic/statistics & numerical data/methods ; Cystic Fibrosis/drug therapy ; Multivariate Analysis ; },
abstract = {In this study, we present an innovative approach for tailoring treatment selection on an individualized basis in the presence of correlated multiple responses, particularly those measured on ordinal scales, including binary responses. Our methodology involves the utilization of rank lists for treatments, generated from probabilities of observing responses of higher order than each level of the ordinal outcome, conditional on patient covariate measurements. We introduce a rank aggregation technique designed to amalgamate multiple lists of ranks, allowing for correlations both within these lists and among elements within each list. Our approach is versatile, accommodating any number of treatments and responses, and is applicable across a wide range of models. Our method offers flexibility by allowing the integration of response weights, enabling customization based on patient and clinician preferences on an individual case basis for optimal treatment decisions. To evaluate the performance of our proposed method in finite samples, we conducted a simulation study. Furthermore, we provide two illustrative examples using data from clinical trials on Cystic Fibrosis and Alzheimer's Disease, demonstrating the application of our proposed procedure in real-world scenarios.},
}

Humans
*Precision Medicine/methods/statistics & numerical data
Alzheimer Disease/drug therapy
Treatment Outcome
Computer Simulation
Models, Statistical
Clinical Trials as Topic/statistics & numerical data/methods
Cystic Fibrosis/drug therapy
Multivariate Analysis

@article {pmid40552638,
year = {2025},
author = {Wang, W and Davis, PB and Qi, X and Gurney, M and Perry, G and Volkow, ND and Kaelber, DC and Xu, R},
title = {Associations of semaglutide with Alzheimer's disease-related dementias in patients with type 2 diabetes: A real-world target trial emulation study.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877251351329},
doi = {10.1177/13872877251351329},
pmid = {40552638},
issn = {1875-8908},
abstract = {BackgroundAlmost half of the dementia cases are preventable. Semaglutide treats several medical conditions that are risk factors for dementia.ObjectiveWe aim to investigate if semaglutide is associated with a decreased risk of dementia.MethodsWe conducted emulation target trials based on a nationwide population-based database of patient electronic health records (EHRs) in the US among 1,710,995 eligible patients with type 2 diabetes (T2D) comparing semaglutide with other antidiabetic medications. First-time diagnosis of Alzheimer's disease-related dementia (ADRD) including vascular dementia, frontotemporal dementia, Lewy body dementia and other dementias were examined using Cox proportional hazards and Kaplan-Meier survival analyses during a 3-year follow-up. Models were adjusted by propensity-score matching.ResultsWe show that semaglutide was associated with a significantly reduced risk of overall ADRD incidence with a hazard ratio ranging from 0.54 (0.49-0.59) compared with insulin, 0.67 (0.61-0.74) compared with metformin, to 0.80 (0.72-0.89) compared with older generation glucagon-like peptide-1 agonists (GLP-1RAs). The association varied for specific dementia types, with significantly reduced risk of vascular dementia and no evidence of associations with frontotemporal and Lewy body dementias.ConclusionsThese findings provide evidence supporting protective effects of semaglutide on dementias in patients with T2D. Future works are needed to establish the causal relationships through randomized clinical trials and to characterize the underlying mechanisms.},
}

@article {pmid40552369,
year = {2025},
author = {Visser, FCW and Kloppenburg-Lagendijk, M and Hempenius, L and Verwey, NA and Perry, M and van Eersel, MEA and van Munster, BC},
title = {From suspicion of cognitive decline to dementia diagnosis: a systematic review of healthcare professionals' considerations and attitudes.},
journal = {Age and ageing},
volume = {54},
number = {6},
pages = {},
doi = {10.1093/ageing/afaf176},
pmid = {40552369},
issn = {1468-2834},
mesh = {Humans ; *Dementia/diagnosis/psychology ; *Attitude of Health Personnel ; *Cognitive Dysfunction/diagnosis/psychology ; *Health Personnel/psychology ; Clinical Decision-Making ; *Health Knowledge, Attitudes, Practice ; },
abstract = {BACKGROUND: Initiating diagnostic testing for dementia is a dynamic and complex process that often involves balancing competing interests. This systematic review aims to provide an overview of healthcare professionals' considerations and attitudes during the process from suspicion of cognitive decline to deciding to initiate diagnostic testing.

METHODS: Databases (PubMed, EMBASE, CINAHL and PsychINFO) were systematically searched on 29 January 2024 for qualitative and mixed-methods studies published since 2005. Search concepts were: 'dementia', 'considerations and attitudes', 'healthcare professionals' and 'diagnosis'. Two screeners independently conducted title/abstract-screening using ASReview (efficient and transparent systematic review machine learning framework), and full-text screening. Findings were analysed by thematic synthesis.

RESULTS: Thirty-three studies were included. Most involved primary care physicians (n = 25), primary care nurses (n = 1) or a combination (n = 7). The overarching phenomenon was that starting the diagnostic workup for dementia is a delicate process. Clusters influencing this process were: complexities arising from the nature of dementia; interaction with the patient and family; individual determinants of primary care practitioners (PCPs); expectations regarding the consequences of a diagnosis; factors related to the healthcare system; and societal factors. Together these clusters form PCPs' strategies and actions for deciding whether to start the diagnostic workup.

CONCLUSION: Initiating the diagnostic workup for dementia is a delicate process influenced by various factors including fear, reluctance and stigma. The different strategies that PCPs use cannot be captured by a single right approach. Recommendations to better support PCPs in navigating this complex process include ensuring consistent communication and clarity about their roles, and promoting interprofessional collaboration.},
}

Humans
*Dementia/diagnosis/psychology
*Attitude of Health Personnel
*Cognitive Dysfunction/diagnosis/psychology
*Health Personnel/psychology
Clinical Decision-Making
*Health Knowledge, Attitudes, Practice

@article {pmid40552323,
year = {2025},
author = {Wang, X and Li, Z and Ma, B and Jia, Q},
title = {Research progress on microglial pyroptosis and inflammasomes: a comprehensive analysis.},
journal = {Frontiers in aging neuroscience},
volume = {17},
number = {},
pages = {1582579},
pmid = {40552323},
issn = {1663-4365},
abstract = {BACKGROUND: Microglial pyroptosis and inflammasome activation play critical roles in neurodegenerative diseases, especially Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS). In recent years, substantial attention has been directed toward elucidating their underlying mechanisms, diagnostic approaches, and prognostic implications. This study aimed to analyze the current research landscape, hotspots, and trends in this field.

METHODS: Articles published over the past decade on microglial pyroptosis and inflammasomes were retrieved from the Web of Science Core Collection (WoSCC) database. A comprehensive analysis was conducted, and high-impact articles were examined in depth.

RESULTS: A total of 958 articles were included. Among these, 664 originated from China, which also had the highest H-index (68), followed by 147 articles from the United States, with an H-index of 48 and the highest centrality (0.68). Southern Medical University (China) was the leading institution in terms of articles (47) and achieved the highest H-index (19). Journal of Neuroinflammation published the most articles (59) in this field. High-impact studies predominantly focused on the roles of microglial pyroptosis and inflammasomes in neurodegenerative diseases, neuroinflammation and therapeutic intervention strategies. Keywords such as "depression," "cell death," "recovery," and "pathogenesis" emerged as research hotspots over the past 3 years.

CONCLUSION: Microglial pyroptosis and inflammasome activation have become research hotspots in neurodegenerative disease, with China and the United States leading in article output and research influence in this field. Southern Medical University (China) is the most influential institution, and the Journal of Neuroinflammation is the most prolific journal. Current research hotspots emphasize elucidating the pathological mechanisms of microglial pyroptosis and inflammasome activation in neurodegenerative diseases, especially in AD, PD, and MS, and exploring potential therapeutic strategies such as MCC950, quercetin, MicroRNA-7, and melatonin. Future studies are expected to focus on mechanism elucidation, disease specificity, dynamic regulation, targeted interventions, and clinical translation to enhance treatment outcomes and prognosis for neurological disorders.},
}