@article {pmid41814062,
year = {2026},
author = {Margarian, S and Chen, Y and Waheed, J and Rezaeimanesh, P and Chiang, VS and Takehara-Nishiuchi, K},
title = {Cost-effective, open-source, automated apparatus for testing transitive inference in mice.},
journal = {Scientific reports},
volume = {16},
number = {1},
pages = {},
pmid = {41814062},
issn = {2045-2322},
abstract = {Transitive inference is a form of reasoning that relies on prior knowledge and benefits survival in diverse species. While initially designed for humans, the transitive inference task has been adapted for mice, allowing for integration with various state-of-the-art manipulation and monitoring tools for mechanistic investigations. Existing paradigms, however, rely on manually presented stimuli, making them time-consuming, labor-intensive, and error-prone. Here, we introduce AutoTI, a fully automated behavioral apparatus that precisely controls the timing of task events and logs timestamps for events and responses. The automation also enables continuous, undisturbed monitoring of spontaneous behavior, allowing for detailed analyses of movement trajectory beyond basic accuracy metrics. Using AutoTI, we developed a robust training protocol that reliably achieved high success rates on transitive tests in mice. Notably, mice exhibited hallmark behavioral patterns seen in humans, including the symbolic distance effect and the serial position effect. AutoTI provides a cost-effective and scalable system for investigating the neurobiological basis of inferential reasoning. It also holds promise for translational research targeting its impairment in autism, schizophrenia, and Alzheimer’s disease, as well as advancing the reasoning capabilities of artificial intelligence.},
}

@article {pmid42020180,
year = {2026},
author = {Tong, FF and Huang, RQ and Gao, Y and Luo, QQ and Chen, YP and Xu, GZ},
title = {[Epidemiological studies of the association between dyslipidemia and Alzheimer's disease].},
journal = {Zhonghua liu xing bing xue za zhi = Zhonghua liuxingbingxue zazhi},
volume = {47},
number = {4},
pages = {767-774},
doi = {10.3760/cma.j.cn112338-20250727-00528},
pmid = {42020180},
issn = {0254-6450},
mesh = {*Alzheimer Disease/epidemiology ; Humans ; *Dyslipidemias/epidemiology/complications ; Risk Factors ; },
abstract = {Alzheimer's disease (AD), as the representative type of dementia among neurodegenerative diseases, has become a major challenge in the field of global public health. Dyslipidemia is considered an acquired risk factor for AD, and both are progressive diseases with long developmental periods, making dyslipidemia a potential predictor of future AD occurrence. Therefore, preventing dyslipidemia is of great significance for the prevention and treatment of AD. Given the global epidemiological background of AD, this article aims to systematically review the association between dyslipidemia and AD, providing theoretical support for the prevention and control of both conditions.},
}

*Alzheimer Disease/epidemiology
Humans
*Dyslipidemias/epidemiology/complications
Risk Factors

@article {pmid42020356,
year = {2026},
author = {Zou, Z and Chen, J and Li, J and Chen, Y},
title = {The iron-energy metabolism axis in Alzheimer's pathogenesis: from mechanisms to interventions.},
journal = {Cell death discovery},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41420-026-03034-w},
pmid = {42020356},
issn = {2058-7716},
abstract = {Alzheimer's disease (AD) is a neurodegenerative disorder with a complex, multifactorial pathogenesis. Growing evidence implicates disturbances in cellular energy metabolism and iron dyshomeostasis as interlinked contributors to pathology. Within this framework, iron accumulation may act as an upstream regulator in certain contexts and stages, while in others it emerges downstream and amplifies ongoing injury. As iron is an essential cofactor for mitochondrial respiration and the tricarboxylic acid cycle, iron imbalance can compromise ATP production and disrupt glucose metabolism, exacerbating neuronal energy deficits. The interplay among iron accumulation, oxidative stress, and neuroinflammation can create vicious cycles that reprogram cellular metabolism and disrupt the critical metabolic coupling between neurons and glial cells. This review synthesizes recent advances in understanding the iron-energy metabolism axis in AD, delineates mechanisms by which iron imbalance precipitates mitochondrial dysfunction and glucose metabolic impairments, and evaluates how these deficits synergize with neuroinflammation and proteinopathy across disease stages. Finally, we appraise emerging therapeutic strategies targeting iron overload and metabolic pathways, discuss their stage-dependent risks and benefits, and outline the need for biomarker-guided approaches to optimize patient selection and treatment timing.},
}

@article {pmid42020486,
year = {2026},
author = {Ahn, JW and Yoon, EJ and Kim, HS and Choi, Y and Jeong, J and Damodar, K and Yoo, YM and Park, D and Joo, SS},
title = {HSN G1 demonstrates multifaceted therapeutic strategy against Alzheimer disease in APP PS1 mouse model.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-49541-9},
pmid = {42020486},
issn = {2045-2322},
abstract = {Current therapeutic approaches for Alzheimer's disease (AD) demonstrate limited efficacy and fail to address disease progression. In the present study, we present HSN-G1, a novel ginsenoside-enriched pharmaceutical formulation that employs a dual-target mechanism through the modulation of amyloid clearance pathways and cholinergic neurotransmission. HSN-G1 demonstrates a reproducible ginsenoside profile enriched with Re (33.27 mg/g), Rd (25.00 mg/g), and Rg3 stereoisomers (12.18 mg/g), ensuring pharmaceutical-grade reproducibility. HSN-G1 enhanced amyloid-beta (Aβ) clearance in microglial cells, with significantly greater effects observed in SRA-overexpressing cells, suggesting SRA-dependent clearance mechanisms. In APP/PS1 transgenic mice, six-week oral administration of HSN-G1 (100-400 mg/kg) elicited significant dose-dependent improvements in cognitive performance. Male mice exhibited more stable and consistent enhancements in both passive avoidance and spatial memory tests compared to vehicle controls (p < 0.001), while both sexes demonstrated comparable reductions in brain Aβ levels (approximately 45%) and differential increases in acetylcholine (73% in males; 55% in females, p < 0.01). HSN-G1 administration enhanced the expression of neurotrophic factors, with NGF upregulation predominantly observed in males, whereas BDNF, CNTF, and GDNF were consistently elevated across both sexes. These findings establish HSN-G1 as a promising disease-modifying agent with standardized composition and therapeutic efficacy, surpassing the limitations of conventional single-target approaches. The superior efficacy of HSN-G1 compared to existing treatments validates its potential for clinical development, highlighting the significance of sex-specific therapeutic responses in future AD therapeutics.},
}

@article {pmid42020643,
year = {2026},
author = {Liu, G and Xie, B and Zhao, J and Lv, L},
title = {LINC00926 promotes microglial M1 polarization and neuroinflammation by sponging miR-383-3p in Alzheimer's disease: a potential diagnostic and therapeutic target.},
journal = {Acta neurologica Belgica},
volume = {},
number = {},
pages = {},
pmid = {42020643},
issn = {2240-2993},
}

@article {pmid42020711,
year = {2026},
author = {Liu, Q and Parrish, RL and Tang, S and Tasaki, S and Bennett, DA and Seyfried, NT and De Jager, PL and Menon, V and Buchman, AS and Yang, J},
title = {Cell-type-aware transcriptome-wide association studies identify 91 independent risk genes for Alzheimer's disease dementia.},
journal = {Communications biology},
volume = {},
number = {},
pages = {},
doi = {10.1038/s42003-026-10030-4},
pmid = {42020711},
issn = {2399-3642},
support = {R35GM138313//U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; R01AG089703//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; },
abstract = {Most existing transcriptome wide association studies (TWASs) of Alzheimer's Disease (AD) dementia only use bulk RNA-seq data and a single statistical method. Here, we utilize an omnibus TWAS (TWAS-O) pipeline that leverages multiple complementary statistical methods to integrate the snRNA-seq dataset (n = 415) of the dorsolateral prefrontal cortex (DLPFC) and the latest GWAS data of AD dementia. We fine-map TWAS risk genes by gene-based conditional analysis and conducted validation analyses by the analogous omnibus proteome-wide association studies (PWAS-O) using bulk proteomics data of DLPFC (n = 716). We identify 223 unique cell-type-aware TWAS risk genes from 350 associations across six major brain cell-types, including 91 fine-mapped independent associations, 11 of which are novel. By PWAS-O, we identify 21 significant PWAS risk genes, including 13 independent associations, which validated 31.9% independent cell-type-aware TWAS associations. By protein-protein interaction network analyses, our novel cell-type-aware TWAS findings are linked to established AD risk genes such as APOE, BIN1, and MAPT.},
}

@article {pmid42020790,
year = {2026},
author = {Ferreira, AFF and Feng, ZP and Sun, HS and Britto, LRG},
title = {Inhibiting the transient receptor potential melastatin 2 channel in microglia: current evidence and therapeutic potential in neurological disorders.},
journal = {Acta pharmacologica Sinica},
volume = {},
number = {},
pages = {},
pmid = {42020790},
issn = {1745-7254},
abstract = {Microglia, the resident immune cells of the central nervous system, play a pivotal role in neuroinflammation and is a key contributor to the onset and progression of various neurological and neurodegenerative diseases. The Transient Receptor Potential Melastatin 2 (TRPM2), a non-selective calcium channel, has emerged as a sensor linking oxidative stress responses and calcium influx. It is expressed in many tissues and cells, including neurons, astrocytes, and microglia. TRPM2 represents one of the molecular mediators regulating microglial activity and function, cytokine production, and microglia-neuron communication. Growing evidence suggests that TRPM2 contributes to the pathological mechanisms underlying diseases such as ischemic stroke, Alzheimer's disease, Parkinson's disease, epilepsy, and neuropathic pain. However, most of the studies mainly explored the TRPM2 involvement in cell death, which has been reviewed by some other authors. In this review, we compile and discuss findings from in vivo and in vitro studies evaluating the role of TRPM2, with a specific focus on its influence over microglial function and neuroinflammatory responses, a field that has been poorly explored. We gathered information from studies reporting, in stroke models, that both pharmacological inhibition and genetic deletion of TRPM2 reduced infarct volume, improved behavioral outcomes, and diminished glial reactivity. In models of neurodegeneration, TRPM2 modulation shows promising effects on neuronal survival and microglial phenotype. In neuropathic pain models, TRPM2 was found to mediate microglial activation and the release of pro-inflammatory mediators, contributing to pain hypersensitivity. However, findings in epilepsy models reveal a more complex picture, with TRPM2 deficiency producing either neuroprotective or deleterious outcomes, highlighting the need for further studies. Although most studies to date support a pathogenic role for TRPM2 in microglia-mediated neuroinflammation, some limitations were highlighted, as the non-selective pharmacological inhibitors available, the inclusion of only males in the majority of studies, and the use of a global TRPM2 knockout. Only two studies employed conditional genetic models to promote specific TRPM2 deletion from microglia, with promising findings. Overall, current evidence indicates TRPM2 as a promising modulator of microglia, with broad implications for the treatment of neurological disorders characterized by chronic inflammation.},
}

@article {pmid42020886,
year = {2026},
author = {Çelik, H and Dalkılınç, E and Aydın, Ş and Çelik, O and Küçükler, S and Topal, A and Akay, R and Gönüllü, S and Yıldız, MO and Alım, B and Özdemir, S},
title = {Delivery of miR-25802 via Small Vesicles Protects Against Mitochondrial Injury, Oxidative Stress, and Neuroinflammation in Alzheimer's Disease.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {},
pmid = {42020886},
issn = {1559-1182},
mesh = {*Oxidative Stress/drug effects ; *MicroRNAs/administration & dosage ; *Alzheimer Disease/pathology/metabolism/genetics ; *Mitochondria/metabolism/pathology/drug effects ; Humans ; Cell Line, Tumor ; Amyloid beta-Peptides/metabolism/toxicity ; *Neuroinflammatory Diseases/pathology/metabolism ; *Extracellular Vesicles/metabolism ; Reactive Oxygen Species/metabolism ; },
abstract = {Mitochondrial dysfunction, oxidative stress, and neuroinflammation play a critical role in the occurrence and progression of Alzheimer's disease (AD). MicroRNAs (miRNAs) have been studied recently as potential therapeutic approaches for AD. In this study, we examined the function and underlying mechanism of microRNA-25802 (miR-25802), a newly discovered miRNA in an AD model. In order to evaluate the levels of oxidative stress, mitochondrial damage and neuroinflammation in neuroblastoma cells, four experimental groups were created: control group (neuroblastoma cells, SH-SY5Y), amyloid beta (Aβ)-induced neuroblastoma cells (SY5Y-Aβ), small extracellular vesicles (sEVs)-only group and miR-25802-loaded small extracellular vesicles (sEV-miR25802) administered group. Neuroinflammation, oxidative stress, mitochondrial damage, tau hyperphosphorylation, and Aβ accumulation were evaluated in Aβ-induced neuroblastoma cells. Oxidative stress was analyzed by measuring reactive oxygen species (ROS), malondialdehyde (MDA), lactate dehydrogenase (LDH), superoxide dismutase (SOD), and glutathione peroxidase 1 (GPX1). Inflammatory markers such as tumor necrosis factor-alpha (TNF-α), intercellular adhesion molecule 1 (ICAM1), and brain-derived neurotrophic factor (BDNF) mRNA levels, a neurotrophic factor, were evaluated by RT-qPCR. Neurofilament light chain (NfL), vascular endothelial growth factor-A (VEGF-A), macrophage migration inhibitory factor (MIF), monocyte chemoattractant protein-1 (MCP-1) and cytochrome c (Cyt-c), mitochondrial transcription factor A (TFAM), PTEN-induced kinase 1 (PINK1) and dynamin-1-like protein (DNM1L) protein levels were determined by ELISA. Mechanistically, sEV-miR25802 were shown to provide anti-inflammatory and neuroprotective effects by regulating neuroinflammation, mitochondrial dysfunction, and oxidative stress. These findings reveal the regulatory role of miR-25802 on neuroinflammation, mitochondrial damage, and oxidative stress and suggest that it may be a potential therapeutic target for AD.},
}

*Oxidative Stress/drug effects
*MicroRNAs/administration & dosage
*Alzheimer Disease/pathology/metabolism/genetics
*Mitochondria/metabolism/pathology/drug effects
Humans
Cell Line, Tumor
Amyloid beta-Peptides/metabolism/toxicity
*Neuroinflammatory Diseases/pathology/metabolism
*Extracellular Vesicles/metabolism
Reactive Oxygen Species/metabolism

@article {pmid42020929,
year = {2026},
author = {Ng, B and Kodosaki, E and Veleva, E and Keshavan, A and Schott, JM and Heslegrave, AJ and Fox, NC and Zetterberg, H},
title = {Aging-related matrix metallopeptidase 10 and osteopontin levels are associated with pathology, cognitive decline, and age at onset in Alzheimer's disease.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {4},
pages = {e71082},
pmid = {42020929},
issn = {1552-5279},
support = {//National Institute for Health and Care Research University College London Hospitals Biomedical Research Centre/ ; UKDRI-1003//UK Dementia Research Institute at UCL/ ; },
mesh = {Humans ; *Osteopontin/cerebrospinal fluid ; *Alzheimer Disease/cerebrospinal fluid/pathology ; Female ; Male ; Aged ; *Aging/cerebrospinal fluid/pathology ; Age of Onset ; Amyloid beta-Peptides/cerebrospinal fluid ; Biomarkers/cerebrospinal fluid ; tau Proteins/cerebrospinal fluid ; *Matrix Metalloproteinase 10/cerebrospinal fluid ; Aged, 80 and over ; *Cognitive Dysfunction/cerebrospinal fluid/pathology ; Middle Aged ; Glial Fibrillary Acidic Protein/cerebrospinal fluid ; Neurofilament Proteins/cerebrospinal fluid ; },
abstract = {INTRODUCTION: Aging is the strongest risk factor for Alzheimer's disease (AD) characterized by amyloid-β (Aβ) plaques and tau tangles in the brain. We aim to compare biological aging-related biomarkers among AD, non-neurodegenerative control (NDC) and non-AD neurodegenerative (Non-AD) individuals to evaluate their clinical utility.

METHODS: We included 137 participants (37 NDC, 67 AD, 33 Non-AD) from the University College London (UCL) Dementia Research Centre and measured matrix metallopeptidase 10 (MMP-10), osteopontin (OPN), neurofilament-light, and glial fibrillary acidic protein in cerebrospinal fluid (CSF) in addition to Aβ/pTau and clinical parameters.

RESULTS: Elevated MMP-10 associated with poorer cognition and later onset specifically in AD, whereas elevated OPN associated with Aβ and tau pathology. MMP-10 and OPN levels improved the differentiation of AD from NDC, and AD from Non-AD, respectively.

DISCUSSION: Our study provides evidence on potential clinical utility of CSF MMP-10 and OPN in diagnosis and supports taking biological aging into consideration in AD research.

HIGHLIGHTS: Elevated osteopontin and matrix metallopeptidase 10 (MMP-10) levels in Alzheimer's disease (AD) cerebrospinal fluid. MMP-10 levels are linked to age at onset and cognitive decline. Osteopontin levels are linked to AD pathologies in the cerebrospinal fluid. MMP-10 levels improved discrimination of AD from non-neurodegenerative controls. Osteopontin levels improved discrimination of AD from other neurodegenerative cases.},
}

Humans
*Osteopontin/cerebrospinal fluid
*Alzheimer Disease/cerebrospinal fluid/pathology
Female
Male
Aged
*Aging/cerebrospinal fluid/pathology
Age of Onset
Amyloid beta-Peptides/cerebrospinal fluid
Biomarkers/cerebrospinal fluid
tau Proteins/cerebrospinal fluid
*Matrix Metalloproteinase 10/cerebrospinal fluid
Aged, 80 and over
*Cognitive Dysfunction/cerebrospinal fluid/pathology
Middle Aged
Glial Fibrillary Acidic Protein/cerebrospinal fluid
Neurofilament Proteins/cerebrospinal fluid

@article {pmid42021299,
year = {2026},
author = {Xie, S and Liang, Y and Pang, Y and Li, Y and Cao, S and Li, Y and Wang, Q and Moghekar, A and Albert, M and Jia, J and , },
title = {Plasma biomarker trajectories across Alzheimer's clinical onset: a 17-year prospective study.},
journal = {Alzheimer's research & therapy},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13195-026-02045-0},
pmid = {42021299},
issn = {1758-9193},
}

@article {pmid42021305,
year = {2026},
author = {Shippy, DC and Sande, ML and Ulland, TK},
title = {Type-1 interferons associated with microglial-mediated neuroinflammation in Alzheimer's disease.},
journal = {Journal of neuroinflammation},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12974-026-03828-w},
pmid = {42021305},
issn = {1742-2094},
support = {R01AG070973/AG/NIA NIH HHS/United States ; },
}

@article {pmid42021321,
year = {2026},
author = {Xi, R and Zheng, X and Zhao, J and Fu, Y},
title = {The SHIP1-inflammatory-lipid axis in Alzheimer's disease: from genetic risk to spatiotemporal mechanistic insights.},
journal = {Journal of neuroinflammation},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12974-026-03819-x},
pmid = {42021321},
issn = {1742-2094},
support = {32400821//the National Natural Science Foundation of China/ ; 82471322//the National Natural Science Foundation of China/ ; SR21500123//the Jiangsu Specially Appointed Professor Program/ ; ZXL2024390//the Gusu Leading Talents in Innovation and Entrepreneurship Program/ ; LG-ADB510202//the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), the Lingang Laboratory/ ; B202306//the Startup Foundation for Hundred-Talent Program of Zhejiang University/ ; SMIDF-150-2025A4//the Brain Health Youth Fund/ ; },
}

@article {pmid42021347,
year = {2026},
author = {Wang, L and Han, L and Liu, S},
title = {Dysfunction of the neurovascular unit as a temporal driver in Alzheimer's pathogenesis.},
journal = {Translational neurodegeneration},
volume = {15},
number = {1},
pages = {},
pmid = {42021347},
issn = {2047-9158},
support = {32530027//National Natural Science Foundation of China/ ; 2021ZD0204400//National Science and Technology Major Project/ ; 2021YFA0805100//Key Technologies Research and Development Program/ ; },
mesh = {*Alzheimer Disease/pathology/physiopathology/metabolism ; Humans ; Animals ; *Brain/pathology/metabolism/blood supply ; *Neurovascular Coupling/physiology ; },
abstract = {Extensive studies have shown that cerebrovascular dysfunction is a critical factor in the onset and progression of Alzheimer's disease (AD). Neurovascular unit (NVU) is impaired in AD brains, including damage of tight junction between endothelial cells, degeneration of pericytes, activation of astrocytes and microglia, and apoptosis of neurons. As decreased cerebral blood flow is observed before amyloid-beta (Aβ) generation, it is supposed that NVU dysfunction may precede and exacerbate the pathological state of AD neural system, and that the events of NVU dysfunction and Aβ deposition synergistically promote AD progression. Technological breakthroughs of three-dimensional NVU organoids, spatial transcriptomics with single-cell resolution, and development of artificial intelligence technology, such as machine learning and deep learning, offer the possibility of constructing accurate functional structural models. Here we systematically review the NVU dysfunction during AD progression as well as the applications of spatial transcriptomics and organoid technology in NVU studies.},
}

*Alzheimer Disease/pathology/physiopathology/metabolism
Humans
Animals
*Brain/pathology/metabolism/blood supply
*Neurovascular Coupling/physiology

@article {pmid42021568,
year = {2026},
author = {Li, Z and Ge, R and Zhao, Z and Xiao, H and Du, C and Lai, Y and Wang, L},
title = {From Bio-Interface Materials to Neural Integration: The Next-Generation Brain-Machine Interfaces Powered by Hydrogels.},
journal = {Advanced materials (Deerfield Beach, Fla.)},
volume = {},
number = {},
pages = {e23422},
doi = {10.1002/adma.202523422},
pmid = {42021568},
issn = {1521-4095},
support = {22322803//National Natural Science Foundation of China/ ; 22375047//National Natural Science Foundation of China/ ; 22361162607//International Cooperation and Exchanges NSFC/ ; 20240305028YY//Key Research Development Program of Jilin Province/ ; 2022YFB3804905//National Key Research and Development Program of China/ ; 2022YFB3804900//National Key Research and Development Program of China/ ; //Graduate Innovation Fund of Jilin University/ ; FZ2025038//State Key Laboratory of New Textile Materials and Advanced Pro- cessing/ ; },
abstract = {Brain-machine interfaces (BMIs), which serve as revolutionary tools for neural recording, modulation, and rehabilitation, are highly dependent on the biocompatibility and mechanical suitability of their electrode materials. Although traditional metal electrodes possess excellent conductivity, their inherent rigidity causes a substantial mechanical mismatch with soft neural tissue, leading to chronic inflammatory responses and poor long-term stability. The emergence of hydrogel electrodes has provided a breakthrough solution to this fundamental limitation. Hydrogels, characterized by their softness, high ionic conductivity, and tissue-like compliance, offer a viable solution to mitigate these issues. This review systematically explores the material properties of hydrogel-integrated BMIs, providing an in-depth investigation of key hydrogel characteristics, including toughness, adhesion, conductivity, and biocompatibility. Additionally, hydrogel-based BMIs are categorized into non-invasive and invasive systems, each defined by its characteristic operational principles and signal-acquisition mechanisms. The study further reviews critical issues, including surgical implantation strategies, multimodal data fusion, integration of artificial intelligence, as well as system integration and clinical translation. From a therapeutic perspective, this work highlights the application of BMIs in treating neurological disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, stroke, neuropathic pain, and depression. Furthermore, this review critically examines the persistent challenges faced by hydrogel-based BMIs and proposes innovative strategies for future development. Ultimately, it outlines a developmental roadmap for next-generation hydrogel-based biotherapeutic technologies aimed at achieving high-fidelity, stable and clinically translatable BMI systems.},
}

@article {pmid42021589,
year = {2026},
author = {Karakasli, AA and Karahan, S and Ayhan, Y},
title = {Response to Commentary on "Clinical Predictors of Alzheimer's Disease-Like Brain Atrophy in Individuals With Memory Complaints".},
journal = {Brain and behavior},
volume = {16},
number = {4},
pages = {e71412},
doi = {10.1002/brb3.71412},
pmid = {42021589},
issn = {2162-3279},
}

@article {pmid42021611,
year = {2026},
author = {Wong, C and Piersol, CV and Chew, F and Lekovitch, C and Shier, V and Morris, M and Martínez, J and Britton, J and Leland, NE},
title = {Lessons Learned From the Implementation of a Pragmatic Trial Evaluating Non-Pharmacological Approaches to Dementia Care in US Nursing Homes.},
journal = {Journal of evaluation in clinical practice},
volume = {32},
number = {3},
pages = {e70451},
pmid = {42021611},
issn = {1365-2753},
support = {IHS-1608-35732/PCORI/Patient-Centered Outcomes Research Institute/United States ; },
mesh = {Humans ; *Nursing Homes/organization & administration ; United States ; *Dementia/therapy ; *Pragmatic Clinical Trials as Topic ; Comparative Effectiveness Research ; },
abstract = {RATIONALE: The consistent delivery of effective evidence into nursing home practice has been shown to enhance quality of care and residents' outcomes. Pragmatic trials enable the evaluation of efficacious interventions in a real-world context, including care of residents living with Alzheimer's Disease and Related Dementias (ADRD). Yet, there are limited pragmatic trials conducted in nursing homes and even less evidence on the strategies to successfully conduct such research in this setting.

OBJECTIVE: To identify the lessons learned from a pragmatic trial and provide recommendations for future successful studies in United States (US) nursing homes.

METHODS: Drawing on a case example of a recently completed pragmatic trial, we used the Comparative Effectiveness Research Framework to guide the thematic analysis of study documentation to identify challenges, strategies used, and recommendations for future pragmatic trials in US nursing homes.

RESULTS: Five themes emerged from this case example: 1) establish and sustain community partner collaboration, 2) context analysis and appropriate implementation plan, 3) study adaptability, 4) data collection in a 'real world' setting, and 5) broad dissemination. Within each theme, strategies we used, challenges we encountered, and recommendations for future studies were identified. Examples of recommendations include empowering community partners to be engaged in the research, co-design with community partners, account for the dynamic nature of the nursing home setting, and maintain communication with organization leaders.

CONCLUSIONS: Successful completion of pragmatic trials in US nursing homes requires active engagement of community partners throughout the research process. The emergent lessons learned and recommendations highlight the complex nature of this care setting, the need to be proactive in implementation planning, and the pivotal role of community partners. Moving forward, there is a need for greater emphasis on systematically sharing experiences more broadly to advance the science of pragmatic trials in US nursing homes.},
}

Humans
*Nursing Homes/organization & administration
United States
*Dementia/therapy
*Pragmatic Clinical Trials as Topic
Comparative Effectiveness Research

@article {pmid42021771,
year = {2026},
author = {Bednorz, A and Religa, D},
title = {Schizophrenia and dementia across the lifespan: epidemiological links, cognitive trajectories, and the pathophysiological interplay.},
journal = {Frontiers in neurology},
volume = {17},
number = {},
pages = {1779076},
pmid = {42021771},
issn = {1664-2295},
abstract = {BACKGROUND: Schizophrenia is a severe psychiatric disorder characterized by persistent cognitive impairment across multiple domains and is increasingly associated with elevated risk of late-life dementia. However, the nature of this association and its underlying mechanisms remain unclear.

OBJECTIVE: This mini-review synthesizes current evidence on dementia risk in schizophrenia, focusing on epidemiology, cognitive trajectories, biological mechanisms, and differential relationships with Alzheimer's disease (AD), vascular dementia (VaD), and frontotemporal dementia (FTD).

RESULTS: Epidemiological studies consistently indicate a two- to threefold increased risk of dementia among individuals with schizophrenia, although estimates vary due to diagnostic and ascertainment biases. Cognitive trajectories are heterogeneous: many patients remain cognitively stable over time, while subgroups demonstrate gradual or accelerated decline associated with negative symptoms, medical comorbidities, and social factors. Current evidence does not support a uniform progression toward Alzheimer-type neurodegeneration. Biomarker, neuropathological, and neuroimaging findings suggest distinct biological profiles, with reduced cognitive reserve, neurodevelopmental vulnerability, accelerated aging processes, and vascular and metabolic burden contributing to dementia risk. Genetic overlap between schizophrenia and AD appears modest, whereas partial clinical and molecular convergence is observed with FTD. Screening tools such as MMSE and MoCA may overestimate dementia prevalence due to longstanding baseline cognitive deficits. Sex differences, late-onset psychosis, and cardiometabolic comorbidities further modify risk trajectories.

CONCLUSION: Dementia risk in schizophrenia likely reflects the interaction of lifelong neurodevelopmental vulnerability with aging-related and modifiable factors rather than a disorder-specific neurodegenerative pathway. Longitudinal biomarker-informed studies and tailored diagnostic frameworks are needed to improve differentiation between chronic cognitive impairment and true neurodegeneration.},
}

@article {pmid42021966,
year = {2026},
author = {Tabi, YA and Meyer, EC},
title = {Autoimmune diseases are associated with increased neurodegenerative and cerebrovascular risk, while systemic corticosteroid exposure shows limited neurodegenerative and modest vascular associations.},
journal = {IBRO neuroscience reports},
volume = {20},
number = {},
pages = {596-608},
pmid = {42021966},
issn = {2667-2421},
abstract = {Systemic autoimmune diseases (AIDs), characterized by chronic peripheral inflammation and frequent vascular comorbidity, are increasingly linked to adverse central nervous system (CNS) outcomes; however, comparative evidence across diverse AIDs and clarification of the roles of vascular burden, inflammatory activity, and immunomodulatory therapy remain limited. Using the TriNetX Global Collaborative Network, we conducted a sequence of retrospective, propensity score-matched cohort experiments in adults aged 50-85 years to quantify incident Parkinson's disease (PD), Alzheimer's disease (AD), transient ischemic attack (TIA), and ischemic stroke across 22 AIDs and to evaluate therapy- and inflammation-stratified risk patterns. In the primary disease-control analysis (Experiment 1 A), AID diagnosis was associated with broadly elevated neurodegenerative and cerebrovascular risk, with stronger and more consistent associations for TIA and ischemic stroke than for PD and AD. To probe robustness, we repeated analyses under tighter control of baseline vascular burden (Experiment 1B: additional matching on circulatory-system diagnoses) and under treatment balancing (Experiment 1 C: additional matching on immune-suppressant exposure). Vascular matching substantially attenuated many associations, particularly for AD, whereas immune-suppressant matching did not materially erase the pervasive cerebrovascular excess. Within-disease CRP stratification (Experiment 2; low vs elevated CRP) did not yield a uniform neurodegenerative gradient but identified a disease-dependent ischemic vulnerability axis in selected inflammatory phenotypes. In treatment substudies, systemic cortisone exposure (Experiment 3) showed little association with PD/AD risk but a modest, heterogeneous increase in TIA/ischemic stroke. Medication-specific strata (Experiment 4) revealed stronger but directionally variable separations, consistent with confounding by indication and severity. Together, these findings position systemic autoimmunity as a robust marker of heightened cerebrovascular risk and a more phenotype-dependent correlate of neurodegenerative risk, supporting intensified vascular surveillance in high-risk AID populations and mechanistic work disentangling inflammation, comorbidity, and treatment.},
}

@article {pmid42022292,
year = {2026},
author = {Llorente-Saguer, I and Gabriele, R and Bradshaw, TY and Leckey, CA and Belder, CRS and Chávez-Gutiérrez, L and de Silva, R and Fox, NC and Wray, S and Oxtoby, NP and Arber, C},
title = {Unbiased data-driven analysis of five amyloid-beta peptides for biomarker investigations in familial Alzheimer's disease.},
journal = {Brain communications},
volume = {8},
number = {2},
pages = {fcag105},
pmid = {42022292},
issn = {2632-1297},
abstract = {Changes to the relative abundance of amyloid-beta (Aβ) peptides are hallmarks of Alzheimer's disease. Induced pluripotent stem cell (iPSC)-derived neurons offer a physiological model of Aβ production. We employed unbiased, data-driven analyses to investigate combinations of Aβ peptides as Alzheimer's disease biomarkers and the relative contribution of peptides to Alzheimer's disease pathogenesis. We measured Aβ37, Aβ38, Aβ40, Aβ42 and Aβ43 in 10 iPSC-neuronal cultures from PSEN1 mutation carriers. We combined these data with published cell model data and used linear weighted combinations to (i) distinguish Alzheimer's disease from controls, and (ii) predict age-at-onset for PSEN1 mutations. Data-driven approaches distinguished Aβ42 and Aβ43 from shorter peptides, providing unbiased evidence for a greater association of Aβ42 and Aβ43 to disease pathogenesis, compared with shorter peptides (Aβ37, Aβ38 and Aβ40). Weighted linear combinations of Aβ peptides outperform Aβ42/40 and provide insights into relative peptide contribution as biomarkers. A representative weighted composite value ratio (wCVR) derived from all data, balancing both disease classification and age-at-onset prediction, was (21 ⋅ A β 37 + 10 ⋅ A β 38 + 69 ⋅ A β 40) / (94 ⋅ A β 42 + 6 ⋅ A β 43) . This work suggests a practical non-parametric harmonization approach to employing Aβ ratios as biomarkers for Alzheimer's disease, from multiple sites and assays. Building on this foundation, we applied a new model using weighted composite value ratios, which outperform existing biomarkers across all tasks. This underscores the value of integrating multiple peptides and assigning optimized weightings. The study confirms the association of Aβ42 and Aβ43 with Alzheimer's disease pathogenesis in a data-driven manner. Peptide weights further provide mechanistic insights into the relative contribution of each peptide to disease, such as a greater contribution of Aβ37 compared to Aβ38. The algorithm used herein can be further refined to improve biomarkers for Alzheimer's disease.},
}

@article {pmid42022333,
year = {2026},
author = {Poisnel, G and Lhérault, M and Palix, C and Turpin, AL and Felisatti, F and Vrillon, A and Paquet, C and Chocat, A and Coulbault, L and De La Sayette, V and Gonneaud, J and Chételat, G and , },
title = {Physical activity attenuates the association between allostatic load and early Alzheimer's disease-related biomarkers in older adults.},
journal = {Alzheimer's & dementia (New York, N. Y.)},
volume = {12},
number = {},
pages = {e70248},
pmid = {42022333},
issn = {2352-8737},
abstract = {INTRODUCTION: Allostatic load (AL), an index of cumulative physiological dysregulation from chronic stress, may contribute to Alzheimer's disease (AD) pathophysiology by accelerating brain aging. Higher AL has been associated with AD-related biomarkers, suggesting a mechanistic connection. Lifestyle factors influence both AL and AD vulnerability, but their moderating role in AL-AD biomarker associations remains unclear.

METHODS: We included 111 cognitively unimpaired older adults from the baseline visit of the Age-Well trial. AL was computed as a composite score of 18 biomarkers spanning neuroendocrine, immune, metabolic, cardiovascular-respiratory, and anthropometric systems. Plasma biomarkers included amyloid beta (Aβ)42, Aβ40, phosphorylated-tau (p-tau231), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL). Physical activity, Mediterranean diet adherence, and cognitive activity were assessed using validated questionnaires. Multiple linear regressions tested associations between AL and (1) AD-related biomarkers and (2) lifestyle factors, as well as their interactions, controlling for age, sex, education, apolipoprotein E ε4 (APOE ε4) status, and glomerular filtration rate (GFR).

RESULTS: Higher AL was associated with higher Aβ42/Aβ40 ratio (b = 0.004, 95% CI [0.001, 0.007], p = 0.010, false discovery rate [FDR] = 0.040) and lower NfL levels (b = -0.035, 95% CI [-0.063, -0.008], p = 0.013, FDR = 0.026). AL correlated negatively with physical activity (b = -0.899, 95% CI [-1.568, -0.230], p = 0.009, FDR = 0.027). A significant interaction was observed between physical activity and AL in relation to the p-tau231/Aβ42 ratio (b = -0.339, 95% CI [-0.588, -0.091], p = 0.008, FDR = 0.032), such that higher AL was associated with lower p-tau231/Aβ42 ratio among more physically active individuals compared with less active individuals.

DISCUSSION: Regular physical activity was associated with a weaker relationship between AL and early AD-related biomarkers in this cross-sectional sample. Longitudinal studies should confirm whether maintaining physical activity attenuates stress-related physiological dysregulation and reduces AD vulnerability.},
}

@article {pmid42022334,
year = {2026},
author = {Bhagunde, P and Penner, N and Willis, BA and Bell, R and Sachdev, P and Charil, A and Irizarry, MC and Hersch, S and Reyderman, L},
title = {Pharmacokinetic/pharmacodynamic analyses of plasma pathophysiology biomarkers in subjects with early Alzheimer's disease following lecanemab treatment.},
journal = {Alzheimer's & dementia (New York, N. Y.)},
volume = {12},
number = {},
pages = {e70246},
pmid = {42022334},
issn = {2352-8737},
abstract = {INTRODUCTION: Lecanemab, a novel monoclonal antibody targeting both neurotoxic amyloid beta (Aβ) protofibrils and Aβ plaques, substantially reduces markers of amyloid and significantly slows clinical decline on multiple measures of cognition and function in early AD in Phase 2 (Study 201) and Phase 3 (Study 301; Clarity AD) studies. In these clinical studies, several plasma biomarkers showed improvements comparing lecanemab with placebo. Herein, we utilized modeling and simulation to evaluate the long-term effects of lecanemab on pathophysiology biomarkers in plasma.

METHODS: Plasma Aβ42/40 ratio, tau phosphorylated at threonine 181 (p-tau181), and glial fibrillary acidic protein (GFAP) data were pooled from lecanemab Phase 2 and 3 studies. Individual serum lecanemab exposure estimated using a population pharmacokinetic model was correlated with plasma biomarker concentrations using indirect response pharmacokinetic/pharmacodynamic (PK/PD) models. Simulations were conducted to evaluate the effect of lecanemab (10 mg/kg IV every 2 weeks, LEC10-BW) after 4 years of continuous treatment, discontinuation after 18 months of treatment or transitioning to less frequent dosing at 18, 24, or 30 months.

RESULTS: PK/PD models describing the change in plasma biomarker levels over time in response to lecanemab treatment were developed, and simulations demonstrated that plasma biomarkers reverted toward pretreatment baseline after cessation of lecanemab treatment, with an average re-accumulation half-life of approximately 1 to 1.5 years, which was faster than amyloid plaque re-accumulation measured by positron emission tomography. Simulations illustrated transitioning to a lecanemab monthly dosing regimen was sufficient to stabilize plasma biomarker concentrations at levels consistent with ongoing inhibition of amyloid pathology and neuroinflammation.

DISCUSSION: PK/PD model simulations demonstrated that plasma biomarkers serve as early indicators of amyloid accumulation and downstream effects. Plasma biomarker simulations suggest the need for ongoing lecanemab treatment even after amyloid plaque clearance. Transition to a less frequent monthly IV regimen at 18 months was shown to maintain the changes in plasma biomarker levels consistent with lecanemab efficacy.},
}

@article {pmid42022545,
year = {2026},
author = {Kruger, K and van der Veen, H and Beigy, M and O'Donovan, SD and van Riel, N and Remie, LB and Aarts, E and Steegenga, W and Smeets, PAM and van Trijp, MPH and de Groot, LCPGM and Vermeiren, Y},
title = {Gut-brain health effects of PREbiotics in older adults with suspected COgnitive DEcline: design of the PRECODE randomised placebo-controlled trial.},
journal = {Frontiers in nutrition},
volume = {13},
number = {},
pages = {1738622},
pmid = {42022545},
issn = {2296-861X},
abstract = {UNLABELLED: Global lifespan is rising, alongside increasing age-related conditions. Cognitive disorders such as dementia, are projected to triple in number by 2050. Currently, no cure is available for Alzheimer's disease (AD), the most common form of dementia, and the need for preventative strategies is paramount. Subjective cognitive decline plus (SCD+) lies on the AD continuum, with increased risk of accelerated cognitive decline, providing an ideal target group for early intervention. The microbiota-gut-brain axis (MGBA) is an emerging avenue for prevention, as dietary fibres may beneficially modulate microbiota and microbial metabolites, such as short chain fatty acids and tryptophan-indoles, resulting in improved gastrointestinal and cognitive functioning. PRECODE is a four-armed, randomised, double-blinded, placebo-controlled trial in 164 older adults (60-79 years) with SCD+ and additional "LIfestyle for BRAin Health" (LIBRA) risk factors. The study aims to investigate 26 weeks of supplementation with chicory inulin, resistant dextrin, and seaweed polysaccharide compared to placebo (maltodextrin) on the MGBA. The primary outcome is effects on neurocognition, assessed by brain activation during working memory load measured with blood-oxygen level dependant functional magnetic resonance imaging (BOLD fMRI) and performance during 2-back task. The secondary outcomes include cognition by neuropsychological test battery, brain and intestinal health parameters, and immune and metabolic markers. Findings may guide new preventative modalities in preclinical AD and provide mechanistic insights into the MGBA in individuals at risk for cognitive decline.

CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/study/NCT06433037.},
}

@article {pmid42022552,
year = {2026},
author = {Jiang, H and Pang, X},
title = {Luteolin as a dietary flavonoid for brain health: modulating neuroinflammation and cognitive decline in neurodegenerative disorders.},
journal = {Frontiers in nutrition},
volume = {13},
number = {},
pages = {1774416},
pmid = {42022552},
issn = {2296-861X},
abstract = {Luteolin, a flavonoid naturally present in a variety of fruits, vegetables, and medicinal plants, has been recognized as a potentially effective neuroprotective nutraceutical because of its remarkable anti-inflammatory, antioxidant, and neurotrophic properties. Increasing evidence suggests that neuroinflammation and oxidative stress are major contributors to cognitive decline and neuronal degeneration in several prominent neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and multiple sclerosis (MS). Luteolin significantly inhibits microglial activation, reduces pro-inflammatory cytokine production, modulates the nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways, and enhances Nrf2-mediated antioxidant mechanisms. Furthermore, it promotes synaptic plasticity through brain-derived neurotrophic factor (BDNF)-associated pathways and mitigates the aggregation of pathological proteins, including Aβ, tau, α-synuclein, and mutant huntingtin. Preclinical studies consistently demonstrate substantial improvements in cognitive function, motor performance, demyelination, and neuronal viability in models of AD, PD, MS, and HD. Preliminary clinical observations also indicate prospective advantages for cognitive function, regulation of inflammatory responses, and alleviation of symptoms, particularly concerning AD and MS. Notwithstanding these encouraging outcomes, obstacles persist due to luteolin's restricted bioavailability, ideal dosing parameters, and the translational discrepancies between experimental models and human pathophysiological conditions. In summary, luteolin emerges as a noteworthy candidate for nutraceutical-oriented approaches designed to alleviate neuroinflammation and cognitive deterioration in the context of neurodegenerative diseases.},
}

@article {pmid42022560,
year = {2026},
author = {Ríos, V and Linares-Pipón, C and Maulén, C and Castro-Álvarez, A and Bradshaw, B and Romero-Parra, J and Cuellar, MA and Martínez-Cifuentes, M and Parra, C},
title = {Conformationally locked 7-aryl tetrahydroisoquinolines as dual acetylcholinesterase inhibitors and antioxidants: role of intramolecular hydrogen bonding and aryl electronics.},
journal = {Frontiers in pharmacology},
volume = {17},
number = {},
pages = {1797738},
pmid = {42022560},
issn = {1663-9812},
abstract = {BACKGROUND: Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder in which cholinergic dysfunction and oxidative stress act as synergistic contributors to cognitive decline and neuronal damage. Multitarget-directed ligands (MTDLs) capable of modulating both acetylcholinesterase (AChE) activity and oxidative stress pathways are promising candidates for disease-modifying therapies.

METHODS: A series of conformationally locked 7-aryl tetrahydroisoquinoline derivatives was synthesized via a tandem cross-metathesis/Michael/annulation strategy. These compounds feature a stable intramolecular O-H···O=C hydrogen bond that enforces a quasi-planar geometry and modulates the electronic properties of the aryl substituent. The compounds were evaluated for their AChE inhibitory activity using Ellman's assay and for antioxidant capacity using the oxygen radical absorbance capacity (ORAC) assay. Molecular docking studies were performed to analyze binding modes within AChE's aromatic gorge, while density functional theory (DFT) calculations were conducted to assess the thermodynamics of hydrogen atom transfer (HAT) and ionization potential (IP) related to antioxidant behavior.

RESULTS: All derivatives exhibited micromolar AChE inhibition (IC50 = 33-54 µM), with structure-activity relationships driven by the electronic nature and π-polarizability of the 7-aryl ring. Docking results revealed a conserved, π-dominated binding pose within the enzyme's active site. ORAC measurements showed substituent-dependent radical-scavenging activity consistent with the electronic trends observed in enzyme inhibition. DFT calculations indicated a thermodynamic preference for hydrogen atom transfer (HAT) from benzylic C-H over phenolic O-H cleavage, supporting the observed antioxidant profile.

CONCLUSION: This study identifies 7-aryl tetrahydroisoquinolines as a novel, mechanistically coherent scaffold for the development of dual-acting neuroprotective agents targeting both cholinergic dysfunction and oxidative stress in Alzheimer's disease. Their tunable electronic properties and preorganized geometry offer a promising foundation for further optimization within the multitarget therapeutic framework.},
}

@article {pmid42022571,
year = {2026},
author = {Patil, VS and Khanal, P and Harish, DR},
title = {Editorial: Targeted drug delivery and mode of action of small molecules in neuroinflammation.},
journal = {Frontiers in pharmacology},
volume = {17},
number = {},
pages = {1782890},
doi = {10.3389/fphar.2026.1782890},
pmid = {42022571},
issn = {1663-9812},
}

@article {pmid42022623,
year = {2026},
author = {Gao, Q and Sun, Z and Wang, Y},
title = {Association of Urinary Perchlorate and Thiocyanate With Cognitive Function in Older Adults: A Cross-Sectional Study.},
journal = {Health science reports},
volume = {9},
number = {3},
pages = {e71965},
pmid = {42022623},
issn = {2398-8835},
abstract = {BACKGROUND AND AIMS: It is well-known that perchlorate, nitrate, and thiocyanate are thyroid-disrupting chemicals. Evidence regarding the cognitive correlates of thyroid-disrupting anions in older adults remains scarce, particularly in population-based studies assessing multiple cognitive domains. Our study aimed to explore the associations between urinary levels of perchlorate, nitrate, and thiocyanate and cognitive function.

METHODS: Participants were obtained from the National Health and Nutritional Examination Survey (NHANES). Urinary levels of perchlorate, nitrate, and thiocyanate were measured by ion chromatography coupled with electrospray tandem mass spectrometry. Cognitive function was evaluated using the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) test, the Animal Fluency Test (AFT), and the Digit Symbol Substitution Test (DSST). Logistic regression analyses were conducted to examine the association between urinary levels of the chemicals and cognitive function.

RESULTS: A total of 993 adults were included with a mean age of 69.5 ± 6.6 years. In multivariable-adjusted logistic regression models, urinary perchlorate was inversely associated with low cognitive function evaluated through the AFT [OR: 0.78; 95% CI (0.63, 0.96); p < 0.05], and urinary thiocyanate was negatively related to low cognitive function assessed by CERAD [OR: 0.70; 95% CI (0.50, 0.97); p < 0.05] and AFT [OR: 0.69; 95% CI (0.50, 0.94); p < 0.05].

CONCLUSION: A relative low urinary perchlorate and thiocyanate were associated with low cognitive function. Higher levels of perchlorate and thiocyanate may be inverse cross-sectional associations in cognitive function.},
}

@article {pmid42022738,
year = {2026},
author = {Makridis, A and Kazeli, K and Katsipis, G and Tzekaki, EE and Pantazaki, AA and Bosch, C and Simon-Carbajo, R and Angelakeris, M},
title = {Biomarker-targeted functionalized magnetic nanoparticles: synthesis and aptamer conjugation optimization toward Alzheimer's disease biosensing.},
journal = {Nanoscale advances},
volume = {},
number = {},
pages = {},
pmid = {42022738},
issn = {2516-0230},
abstract = {Magnetic-plasmonic hybrid nanoparticles are gaining prominence in biomedical diagnostics due to their dual functionality, combining magnetic manipulation and signal enhancement. A major challenge remains the reproducible synthesis of core-shell nanostructures with controlled size, composition, and stability. In this work, we present a robust two-step aqueous co-precipitation method to produce gold/magnetite nanoparticles, for early Alzheimer's disease diagnosis, based on biomarker's aptamer-based biosensing. Magnetite nanoparticles were first synthesized with high saturation magnetization, followed by controlled gold shell growth via citrate-assisted reduction. Systematic tuning of gold precursor ratios and washing steps enabled precise control over the shell structure and surface properties. The nanoparticles were extensively characterized using X-ray diffraction, dynamic light scattering, zeta potential analysis, vibrating sample magnetometry, ultraviolet-visible spectroscopy, and inductively coupled plasma measurements, outlining optimal characteristics: distinct core-shell morphology, ferrimagnetic behavior, strong localized surface plasmon resonance, and high colloidal stability. Beyond synthesis and characterization of nanoparticles, this study also introduces an innovative aptamer conjugation protocol tailored for maximizing their binding efficiency, thereby enhancing early recognition of certain neurodegenerative biomarkers: Aβ-40, Aβ-42, TBA and GFAP. The tailored features of the gold/magnetite nanoparticles allow fine control over particle size and aptamer loading, making this work a valuable tool for designing structurally, magnetically, and physicochemically optimized carriers for neurodegenerative disease diagnostics. Collectively, these results establish a scalable and functional platform suitable for next-generation biosensing applications in the early detection of Alzheimer's disease.},
}

@article {pmid42022743,
year = {2026},
author = {Dai, D and Chen, J and Guo, X and Sun, J and Yi, H},
title = {Mechanistic research on the vestibular-hippocampal pathway in neurodegenerative diseases: an integrative perspective from molecular to behavioral levels.},
journal = {Frontiers in neuroscience},
volume = {20},
number = {},
pages = {1779268},
pmid = {42022743},
issn = {1662-4548},
abstract = {This paper systematically reviews the pivotal role and bidirectional regulatory mechanisms of the Vestibular-hippocampal pathway in the onset and progression of neurodegenerative diseases (such as Alzheimer's disease), focusing on the common comorbidity of vestibular dysfunction and cognitive decline. Evidence spanning molecular to behavioral levels indicates that vestibular signal loss can induce hippocampal atrophy and spatial memory impairment through neuroinflammation, impaired synaptic plasticity, and disrupted theta rhythms. Conversely, hippocampal degeneration further impairs vestibular information integration, creating a vicious cycle. Intervention approaches such as vestibular rehabilitation, cognitive training, and neurostimulation show potential for slowing co-morbidity progression. Future research should focus on developing animal models simulating vestibular-neurodegenerative co-morbidity, conducting longitudinal clinical validation using multimodal imaging and electrophysiology techniques, and optimizing neuromodulation strategies and targeted molecular interventions to advance this mechanism toward early diagnosis and precision treatment.},
}

@article {pmid42022958,
year = {2026},
author = {Chien, SC and Chien, YC and Wang, HJ and Chen, JC},
title = {A ZIF-8-modified electrochemical biosensor for sensitive Aβ aggregation monitoring and Alzheimer's disease drug screening.},
journal = {RSC advances},
volume = {16},
number = {23},
pages = {20855-20865},
pmid = {42022958},
issn = {2046-2069},
abstract = {Alzheimer's disease (AD) is an irreversible neurodegenerative disorder driven by the abnormal aggregation of β-amyloid (Aβ) into oligomers, fibrils, and plaques. Current therapeutic strategies primarily alleviate symptoms but struggle to prevent aggregation due to the dynamic nature of Aβ species and prolonged drug development cycles. Sensitive and real-time monitoring of Aβ structural transitions is therefore essential for understanding disease progression and evaluating potential inhibitors. In this study, we developed a ZIF-8-modified electrochemical biosensor capable of translating Aβ42 conformational changes into quantifiable current signals, providing a promising platform for monitoring dynamic aggregation. The aggregation behavior of Aβ42 was systematically characterized using dynamic light scattering (DLS), electrochemical measurements, and Thioflavin T (ThT) fluorescence combined with ultrafiltration. A critical transition from the lag to the growth phase was observed at 24 h, with aggregates exceeding ∼60 nm undergoing irreversible fibrillization. The ZIF-8-modified electrochemical sensor detected early-stage structural rearrangements with superior sensitivity compared to conventional ThT fluorescence, revealing subtle oligomer formation. Quantitative current measurements allowed continuous monitoring of aggregation kinetics, highlighting the temporal resolution of the platform. Validation experiments with curcumin treatment demonstrated strong inhibitory effects between 18 and 24 h, delaying fibrillization, reducing late-stage β-sheet accumulation, and decreasing aggregate size by approximately 25%. In addition, the sensor successfully distinguished minor differences in structural transitions under varying inhibitor concentrations, demonstrating its capability for high-resolution, real-time assessment of aggregation dynamics and drug efficacy. This ZIF-8-modified electrochemical biosensor provides high-sensitivity, dynamic monitoring of Aβ42 aggregation and drug-induced inhibition, offering a valuable tool for mechanistic studies of protein aggregation pathology. By enabling early detection of structural transitions and real-time evaluation of inhibitors, this platform has the potential to accelerate therapeutic screening and improve the development of effective interventions for AD.},
}

@article {pmid42023255,
year = {2026},
author = {Valle, ML and Arienzo, D},
title = {Preclinical advances in antibodies against N-terminal Aβ4-x species for Alzheimer's disease and cerebral amyloid angiopathy.},
journal = {Ibrain},
volume = {12},
number = {1},
pages = {52-64},
pmid = {42023255},
issn = {2769-2795},
abstract = {Alzheimer's disease (AD) pathogenesis is characterized by the accumulation of amyloid beta (Aβ) deposits in the cerebral parenchyma and vasculature, a condition referred to as cerebral amyloid angiopathy (CAA). Besides the full-length form, Aβ deposits showed a highly heterogenous composition due to the action of different proteolytic enzymes. N-terminal Aβ peptides have shown higher aggregation propensity and toxicity compared to the other truncated forms, with species starting at residue phenylalanine 4 (Aβ4-x) being more neurotoxic than the others. Thus, Aβ4-x species have drawn attention in AD pathogenesis, potentially offering novel therapeutic targets to halt or reverse disease progression. Antibodies targeting specifically Aβ4-x species were designed with the aim of preventing their aggregation and promoting their clearance counterbalancing their neurotoxic effect. This work provides an update on monoclonal and polyclonal antibodies developed to specifically target Aβ4-x species in AD and CAA preclinical studies (in vitro and in vivo models).},
}

@article {pmid42023276,
year = {2026},
author = {Kuan, JH and Raghavan, RS and Koh, DLW and Tan, WY and Iezhitsa, I and Agarwal, R},
title = {Navigating the cholesterol maze: Key insights on use of statins in neurodegenerative disorders.},
journal = {Neuroprotection (Chichester, England)},
volume = {4},
number = {1},
pages = {30-47},
pmid = {42023276},
issn = {2770-730X},
abstract = {Neurodegenerative diseases such as Alzheimer's (AD), Parkinson's (PD), Huntington's (HD), and multiple sclerosis (MS) involve progressive neuronal loss driven by dysregulated neurotransmission, neuroinflammation, oxidative stress, and mitochondrial dysfunction. Cholesterol metabolism has emerged as a critical factor involved with both central and peripheral dysregulation contributing to pathology. This review synthesizes current evidence on cholesterol's role in neurodegeneration and evaluates the therapeutic potential of statins, which act via cholesterol-dependent and other pleiotropic mechanisms. A PubMed search covering 1985-2025 publications was conducted using terms related to neurodegenerative diseases, statins, cholesterol metabolism, neuroinflammation, oxidative stress, mitochondrial dysfunction, and neuroprotection. Studies were selected to highlight mechanistic insights into cholesterol regulation in the nervous system and clinical data on statin use. Neuronal loss in neurodegeneration is driven by processes including excitotoxicity, inflammation, and mitochondrial dysfunction. Excessive reactive oxygen species activate apoptotic pathways involving BAX, BAK, and p53. Dysregulated cholesterol metabolism is a significant contributor: In AD, the ApoE allele ε4 (ApoE4) links elevated cholesterol to amyloid-β (Aβ) accumulation and cognitive decline; in PD, cholesterol shows mixed effects, with some studies suggesting protection and others linking high levels to α-synuclein aggregation and mitochondrial impairment. In HD reduced cholesterol biosynthesis correlates with neuronal loss, while MS associates with elevated cholesterol and cognitive dysfunction. Statins, widely used cholesterol-lowering agents, reduce Aβ production, enhance its clearance, and improve synaptic function. Beyond lipid lowering, they exert anti-inflammatory, antioxidant, and anti-apoptotic effects. Clinical outcomes remain mixed, with benefits influenced by statin type, dose, treatment duration, disease stage, and patient genetics. Statins show multifaceted neuroprotective potential through cholesterol-dependent and independent pathways. While preclinical data are encouraging, clinical evidence is heterogeneous. Long-term, stratified trials are needed to clarify efficacy, and tailoring therapy to disease-specific mechanisms may offer a viable strategy for mitigating neurodegeneration and enhancing neuronal survival.},
}

@article {pmid42023285,
year = {2026},
author = {Cao, B and Qi, Q and Hutchinson, S and Ferguson, D and Malhotra, P and Koychev, I and O'Brien, JT and Bridgeman, K and Ritchie, CW and Lawlor, B and Naci, L and , },
title = {The relative contribution of modifiable and non-modifiable factors for determining cognition in mid-life individuals at risk for late-life Alzheimer's disease.},
journal = {Alzheimer's & dementia (Amsterdam, Netherlands)},
volume = {18},
number = {2},
pages = {e70303},
pmid = {42023285},
issn = {2352-8729},
abstract = {INTRODUCTION: It remains unknown whether cognitive reserve contributors can protect against dementia from mid-life, in the context of several modifiable and non-modifiable risk factors, including family history and inherited risk for late-life dementia.

METHODS: We leveraged PREVENT Dementia, a large multisite study of healthy mid-life at-risk individuals (N  =  700) and used canonical correlation analysis (CCA) to investigate multivariate associations between 13 cognitive tasks, 10 modifiable and four non-modifiable risks, and three reserve contributors.

RESULTS: The CCA identified a significant canonical mode (r = 0.486, p (FWE) < 0.001) between dementia risk, reserve contributors, and cognition. The key finding was that modifiable stimulating activities showed the strongest positive association with cognition. Depressive symptoms and traumatic brain injury were the top two modifiable risk factors negatively associated with cognition.

DISCUSSION: These results highlight the strong potential of early, cost-effective, and multifactorial dementia prevention interventions that target both modifiable risk reduction and boosting of cognitive reserve from mid-life.},
}

@article {pmid42023454,
year = {2026},
author = {Qi, W and Wang, J and Gao, X and Liu, Y},
title = {Impact of Sleep Quality on Cognitive Function in Elderly Patients With Alzheimer's Disease.},
journal = {Actas espanolas de psiquiatria},
volume = {54},
number = {2},
pages = {328-334},
doi = {10.62641/aep.v54i2.2126},
pmid = {42023454},
issn = {1578-2735},
mesh = {Humans ; Male ; Female ; *Alzheimer Disease/complications/physiopathology/psychology ; Aged ; Retrospective Studies ; *Sleep Quality ; Aged, 80 and over ; *Cognition/physiology ; *Cognitive Dysfunction/physiopathology ; Polysomnography ; Severity of Illness Index ; },
abstract = {OBJECTIVE: This study aimed to analyse the effect of sleep quality on cognitive function in elderly patients with Alzheimer's disease (AD).

METHODS: This retrospective study extracted clinical data from the hospital's electronic medical record system for elderly patients with AD admitted to the Departments of Neurology or Geriatrics between June 2022 and June 2024. Cognitive function was assessed using the MiniMental State Examination (MMSE), subjective sleep quality was evaluated with the Athens Insomnia Scale (AIS) and objective sleep architecture parameters were measured via overnight polysomnography (PSG). Participants were stratified into mild and moderate-to-severe cognitive impairment groups according to their MMSE scores. General characteristics and sleep-related indicators were compared between the two groups. A binary logistic regression model was employed to analyse independent factors influencing cognitive impairment severity. In this model, cognitive impairment severity served as the dependent variable, and PSG parameters and AIS score served as the core independent variables. Adjustments were made for potential confounding factors, including age, gender, years of education, disease duration, Hospital Anxiety and Depression Scale (HADS) scores and  Instrumental Activities of Daily Living Scale (IADL) scores.

RESULTS: The cohort comprised 61 (40.67%) moderate-to-severe and 89 (59.33%) mild impairment patients. Compared with the mild impairment group, the moderate-to-severe group showed significantly poorer subjective (higher AIS) and objective sleep profiles, including reduced total sleep time, efficiency, and N2/N3 sleep and increased N1 sleep, latency and awakenings (p < 0.05). Adjusted regression identified the N3 stage/total sleep time ratio as a protective factor (odds ratio [OR] = 0.720, 95% CI: 0.576-0.900, p = 0.004) and the AIS score (OR = 1.850, 95% CI: 1.405-2.434, p < 0.001) and number of awakenings (OR = 3.101, 95% CI: 1.879-5.116, p < 0.001) as independent risk factors.

CONCLUSION: In elderly patients with AD, impaired objective sleep architecture and subjective insomnia are significantly associated with poor cognitive function. This study highlighted sleep parameters as potential indicators for cognitive status assessment.},
}

Humans
Male
Female
*Alzheimer Disease/complications/physiopathology/psychology
Aged
Retrospective Studies
*Sleep Quality
Aged, 80 and over
*Cognition/physiology
*Cognitive Dysfunction/physiopathology
Polysomnography
Severity of Illness Index

@article {pmid42023459,
year = {2026},
author = {Zhou, H and Liu, Y and Li, K and Mou, S and Cao, X and Chen, Q},
title = {The Role of Exosome-miRNA as Biomarkers of Alzheimer's Disease: A Systematic Review of Case-Control and Longitudinal Studies.},
journal = {Actas espanolas de psiquiatria},
volume = {54},
number = {2},
pages = {556-567},
doi = {10.62641/aep.v54i2.2109},
pmid = {42023459},
issn = {1578-2735},
mesh = {Humans ; *Alzheimer Disease/diagnosis/genetics/blood ; *Exosomes/genetics/metabolism ; *MicroRNAs ; Biomarkers/blood ; Case-Control Studies ; Longitudinal Studies ; },
abstract = {Alzheimer's disease (AD) is a progressive neurodegenerative disorder, and its diagnosis emains challenging. Exosomal microRNAs (miRNAs), due to their stability, tissue specificity, and ability to cross the blood-brain barrier, show significant promise as ideal biomarkers for AD. The present study aimed to systematically elucidate the relationship between the exosomal miRNA expression changes and AD pathogenesis (including Aβ deposition, Tau protein phosphorylation, and neuroinflammation) and to evaluate their potential utility in clinical screening and therapeutic interventions. A systematic literature search was conducted in the PubMed and Web of Science databases to identify human case-control or cohort studies reporting expressions of mature exosomal miRNAs in the serum, plasma, cerebrospinal fluid, saliva, or central nervous system cells. After evaluating the quality of the studies using the National Institutes of Health quality assessment tool, the identified differentially expressed miRNAs were summarized and functionally integrated. Among the 390 screened records, 48 studies (n = 3046 AD patients) met the inclusion criteria. The analysis identified 120 exosomal miRNAs that are differentially expressed at different AD ages. Six miRNAs (miR-125b, miR-146a, miR-193b, miR-185-5p, miR-29b/c, miR-21-5p) were most consistently reported and showed significant correlation with AD pathology.},
}

Humans
*Alzheimer Disease/diagnosis/genetics/blood
*Exosomes/genetics/metabolism
*MicroRNAs
Biomarkers/blood
Case-Control Studies
Longitudinal Studies

@article {pmid42023593,
year = {2026},
author = {Li, Z and Chen, X and Liu, J and Mo, S and Yu, Y and Sun, Z and Gao, X and Su, D},
title = {Combining Engineered Probe Library with Tiered Screening for the Rational Discovery of Alzheimer's Diagnostic Probe with an Enhanced Signal-to-Noise Ratio.},
journal = {Analytical chemistry},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.analchem.6c00088},
pmid = {42023593},
issn = {1520-6882},
abstract = {Alzheimer's disease (AD) is neuropathologically defined by the deposition of β-amyloid (Aβ) plaques, a key diagnostic biomarker. However, current fluorescence probes targeting Aβ plaques are often limited by poor blood-brain barrier (BBB) penetration and short blood circulation half-lives, resulting in insufficient signal-to-noise ratios for in vivo imaging. To address this, we developed a rationally engineered near-infrared (NIR) fluorescent molecular probe library and implemented a tiered, closed-loop screening strategy for the discovery of probes, enabling high-fidelity in situ visualization of Aβ plaques. Through this integrated approach, we identified ADFP-2, which displays a high binding affinity for Aβ aggregates and exhibits a 34-fold fluorescence enhancement upon binding. Notably, ADFP-2 demonstrates optimal BBB penetrability and a prolonged circulation time, facilitating high-contrast in vivo imaging of Aβ deposits. This study not only provides a potent molecular tool for the early diagnosis of AD but also validates a systematic and efficient framework for probe discovery and optimization through engineered libraries and tiered screening.},
}

@article {pmid42023629,
year = {2026},
author = {Li, Y and Li, S and Ma, J and Zhao, J and Ning, N and Sun, J},
title = {The role of synaptic plasticity in Alzheimer's disease: from molecular mechanisms to therapeutic targets.},
journal = {Folia neuropathologica},
volume = {64},
number = {1},
pages = {1-11},
doi = {10.5114/fn.2025.156508},
pmid = {42023629},
issn = {1509-572X},
mesh = {*Alzheimer Disease/physiopathology/pathology/metabolism/therapy ; Humans ; *Neuronal Plasticity/physiology ; Animals ; tau Proteins/metabolism ; Amyloid beta-Peptides/metabolism ; },
abstract = {Alzheimer's disease (AD) is characterized by a complex pathophysiology, involving abnormal aggregation of amyloid b (Ab) and tau proteins, neuroinflammatory responses, and significant synaptic dysfunction, which collectively contribute to cognitive decline. This review offers a novel perspective by focusing on the pivotal role of synaptic plasticity in the pathogenesis of AD, underscoring its potential as a therapeutic target. The study uniquely synthesizes current molecular and clinical research to illustrate how Ab and tau pathologies disrupt synaptic signaling and structure, further exacerbated by neuroinflammation. We explore both pharmacological interventions, such as BACE1 inhibitors and tau stabilizers, and non-pharmacological strategies, including cognitive therapy and neuromodulation techniques, which have shown promise in modulating synaptic plasticity and slowing cognitive deterioration. Despite these advancements, the field faces significant challenges, including the complexity of AD's underlying mechanisms and limitations in early diagnosis. This review not only highlights the significance of synaptic plasticity in AD but also proposes future research directions that could lead to innovative therapeutic approaches, offering new hope for effective treatment strategies.},
}

*Alzheimer Disease/physiopathology/pathology/metabolism/therapy
Humans
*Neuronal Plasticity/physiology
Animals
tau Proteins/metabolism
Amyloid beta-Peptides/metabolism

@article {pmid42023673,
year = {2026},
author = {Shofner, S and Morgan, K and Luu, P and Shusterman, R and Doncov, A and Heys, J and Ray, L and Lim, MM and Tucker, D},
title = {tES Synchronization of Slow Oscillations in N3 Sleep Decreases Brain Electrical Impedance: Implications for Improved Brain Waste Clearance.},
journal = {Sleep},
volume = {},
number = {},
pages = {},
doi = {10.1093/sleep/zsag079},
pmid = {42023673},
issn = {1550-9109},
abstract = {The age-related impairment of glial-lymph (glymphatic) mechanisms for brain waste clearance has been suspected as a causal factor in the accumulation of toxic metabolites, including amyloid beta and tau proteins in Alzheimer's Disease and alpha synuclein in Parkinson's Disease and Lewy Body Dementia. Because electrical current at low frequencies flows preferentially through extracellular space (ECS), measures of brain electrical impedance may track changes over time in ECS as a function of CSF dynamics that are important to brain waste clearance in sleep. We applied a single-frequency measure of electrical impedance in a study of transcranial electrical stimulation (tES) to enhance deep N3 sleep in healthy adults, using a novel method for estimating the intracranial impedance compartment through separately estimating and subtracting the electrode-skin impedance. The results suggest that, regardless of tES, brain impedance slowly decreases over the course of the night's sleep versus waking, with a marked decrease in REM. Furthermore, the therapeutic tES protocol (applied to synchronize and enhance slow oscillations of N3) resulted in significant brain impedance decreases in the transition from N2 to N3 (as well as in REM), consistent with the fast MRI evidence of respiration-linked CSF inflow at these intervals.},
}

@article {pmid42023677,
year = {2026},
author = {González, KA and Tarraf, W and Pa, J and Banks, SJ and Bangen, KJ and Galasko, D and Gallo, LC and Stickel, AM and Anita, NZ and Márquez, F and Filigrana, P and Isasi, CR and Daviglus, M and Testai, FD and Lamar, M and DeCarli, C and González, HM},
title = {Diabetes, hyperglycemia, and ATN blood biomarkers in Hispanic/Latino populations: SOL-INCA study.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {4},
pages = {e71223},
doi = {10.1002/alz.71223},
pmid = {42023677},
issn = {1552-5279},
support = {R01AG075758/AG/NIA NIH HHS/United States ; R56AG048642/AG/NIA NIH HHS/United States ; RF1AG054548/AG/NIA NIH HHS/United States ; RF1AG061022/AG/NIA NIH HHS/United States ; //National Science Foundation Graduate Research Fellowship Program/ ; //National Heart, Lung and Blood Institute/ ; HHSN268201300001I / N01-HC-65233//University of North Carolina/ ; HHSN268201300004I / N01-HC-65234//University of Miami/ ; HHSN268201300002I/N01-HC-65235//Albert Einstein College of Medicine/ ; HHSN268201300003I / N01- HC-65236//University of Illinois at Chicago/ ; HHSN268201300005I / N01-HC-65237//San Diego State University/ ; /MD/NIMHD NIH HHS/United States ; /DE/NIDCR NIH HHS/United States ; /DC/NIDCD NIH HHS/United States ; /NS/NINDS NIH HHS/United States ; /DK/NIDDK NIH HHS/United States ; //Office of Dietary Supplements/ ; },
mesh = {Humans ; Biomarkers/blood ; Male ; Female ; *tau Proteins/blood ; *Hispanic or Latino/statistics & numerical data ; *Amyloid beta-Peptides/blood ; *Diabetes Mellitus/blood/ethnology ; Neurofilament Proteins/blood ; Aged ; Middle Aged ; *Hyperglycemia/blood/ethnology ; Glycated Hemoglobin/metabolism ; Glial Fibrillary Acidic Protein/blood ; Peptide Fragments/blood ; White ; },
abstract = {INTRODUCTION: Research studying associations between plasma amyloid-tau-neurodegeneration (ATN) biomarkers and vascular factors, such as diabetes, is limited. We sought to examine associations between diabetes status and plasma ATN biomarkers in diverse Hispanic/Latino individuals.

METHODS: We used data from the Hispanic Community Health Study/Study of Latinos and the Study of Latinos-Investigation of Neurocognitive Aging ancillary studies. Our exposures included diabetes status and hemoglobin A1c (HbA1c) percentage. Outcomes included amyloid beta (Aβ) 42/40 ratio, phosphorylated tau 181 (p-tau181), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP).

RESULTS: The final analytic sample was N = 6264. Diabetes, but not prediabetes, was associated with higher NfL and p-tau181 and lower Aβ42/40 ratio. Elevated HbA1c percentage was associated with higher NfL, p-tau181, and GFAP and lower Aβ42/40.

DISCUSSION: Diabetes was associated with plasma biomarkers of Alzheimer's disease pathology and non-specific neurodegeneration. Reducing diabetes prevalence could be beneficial for lowering dementia risk in this population.},
}

Humans
Biomarkers/blood
Male
Female
*tau Proteins/blood
*Hispanic or Latino/statistics & numerical data
*Amyloid beta-Peptides/blood
*Diabetes Mellitus/blood/ethnology
Neurofilament Proteins/blood
Aged
Middle Aged
*Hyperglycemia/blood/ethnology
Glycated Hemoglobin/metabolism
Glial Fibrillary Acidic Protein/blood
Peptide Fragments/blood
White

@article {pmid42024020,
year = {2026},
author = {Chun, H and Lee, HW and Hong, SB and Ha, SS and Yoon, KJ},
title = {Home-based transcranial photobiomodulation improves cognitive function in mild cognitive impairment due to Alzheimer's disease: A randomized, double-blind, placebo-controlled confirmatory trial.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261443973},
doi = {10.1177/13872877261443973},
pmid = {42024020},
issn = {1875-8908},
abstract = {BackgroundAlzheimer's disease (AD) is a progressive neurodegenerative disorder in which early bioenergetic dysfunction is increasingly implicated in its pathogenesis. Transcranial photobiomodulation (tPBM), a non-invasive neuromodulation using near-infrared light, has shown promise in improving cerebral metabolism and cognitive function.ObjectiveTo assess the safety and efficacy of a home-administered tPBM intervention in individuals with mild cognitive impairment (MCI) due to AD.MethodsIn this randomized clinical trial, 80 participants meeting the NIA-AA criteria for MCI due to AD were recruited. Participants self-administered a tPBM device emitting 808 nm near-infrared light over the bilateral dorsolateral prefrontal cortex, six times weekly for 12 weeks. The primary outcome was the change in MoCA-K score from baseline to week 13. Secondary outcomes included K-MMSE2, CERAD-K, and GDepS scores.ResultsActive tPBM significantly improved cognitive performance compared with the placebo. Mean MoCA-K scores increased by 3.87 ± 2.51 points in the active group versus a 0.74 ± 2.85 point decline in the placebo group (p < 0.001). K-MMSE2 scores improved significantly (p < 0.001). CERAD-K showed a significant between-group difference at week 13 (p < 0.001), while GDepS scores remained unchanged. No device-related adverse events occurred, and adherence to home-based treatment was high.Conclusions12 weeks of home-administered tPBM safely and significantly improved cognitive function in individuals with MCI due to AD. The observed benefits are consistent with enhanced mitochondrial metabolism, cerebral perfusion, and synaptic efficiency. These findings support tPBM as a promising, non-pharmacological treatment for MCI due to AD and as a preventative strategy against AD.Trial RegistrationKorean Clinical Research Information Service (CRiS), https://cris.nih.go.kr, KCT0011155.},
}

@article {pmid42024038,
year = {2026},
author = {Horakova, H and Jester, DJ and Vohradkova, T and Sheardova, K and Ondrej, J and Matuskova, V and Fendrych Mazancova, A and Nikolai, T and Andel, R and Lerch, O and Laczó, J and Hort, J and Vyhnalek, M},
title = {Evaluating self- and informant-reported complaints as predictors of cognitive progression in subjective cognitive decline: A clinically-based evaluation.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261443656},
doi = {10.1177/13872877261443656},
pmid = {42024038},
issn = {1875-8908},
abstract = {BackgroundSubjective cognitive complaints (SCCs) in cognitively normal older adults are associated with increased dementia risk. However, it remains uncertain which complaints best predict cognitive decline and whether predictive value differs between patient and informant reports.ObjectiveTo examine associations between self- and informant-reported total scores and individual items from the Questionnaire of Cognitive Complaints (QPC) and longitudinal cognitive decline in individuals with subjective cognitive decline (SCD).Methods261 individuals with SCD from the prospective Czech Brain Aging Study were followed longitudinally (mean 4.2-year follow-up). Linear mixed-effects models (random intercepts), adjusted for age, sex, and education, were estimated separately for self- and informant-reported QPC-total scores and for individual QPC-items to examine associations with change over time in global cognition, memory, and executive function/processing speed cognitive composites.ResultsHigher QPC-total scores predicted steeper decline across all cognitive composites in both self- and informant-reports, with modest effects. At the item level, after Bonferroni correction, informant-reported impressions of memory change and worse memory compared with peers were associated with a more pronounced decline across all cognitive composites exceeding the predictive value of the QPC-total score. Several other memory- and non-memory-related complaints showed associations in the same direction but did not consistently remain significant after correction.ConclusionsIn older adults with SCD, focusing on specific SCCs, particularly informant-reported memory complaints, rather than relying solely on global SCC score, allows more targeted identification of individuals whose complaints are most consistently associated with longitudinal cognitive decline. Structured assessments integrating informant perspective may improve early risk stratification.},
}

@article {pmid42024046,
year = {2026},
author = {Rodriguez-Reyes, RF and Guo, H and Luongo, M and Gomez-Isaza, L and Pletnikova, O and Troncoso, JC and Morris, M},
title = {Amyloid plaques associated with shift in patterns of hippocampal tau pathology in middle age.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261443643},
doi = {10.1177/13872877261443643},
pmid = {42024046},
issn = {1875-8908},
abstract = {BackgroundTau pathology begins to accumulate in the medial temporal lobe in many individuals in middle age. Some individuals develop amyloid pathology, more advanced tau pathology (Braak stage), and higher levels of CA1 hippocampal tau pathology in the context of Alzheimer's disease. Others never develop significant amyloid pathology; in these cases, hippocampal tau pathology can be CA2-predominant and tends not to accumulate past intermediate stages. But factors associated with the early formation of these tau patterns is unclear.ObjectiveThe objective of this study is to examine demographic, genetic (APOE), and pathologic factors associated with the emergence of hippocampal tau pathology patterns in middle age.MethodsWe identified 89 individuals with hippocampal tau pathology ages 65 and younger. These cases were assessed for tau stage, amyloid plaques, and APOE4 status. Hippocampal tau pathology in CA1 and CA2 was scored semi-quantitatively.ResultsIn a younger aging population, tau pathology initially deposits at low levels in CA1 and CA2. In the presence of amyloid, tau pathology is increased in both CA1 and CA2, but with a shift toward a greater proportion of cases with higher tau pathology in CA1.ConclusionsPatterns of tau pathology in middle age are strongly associated with amyloid plaques, including increased CA1 and CA2 pathology and a greater proportion of CA1-predominant cases. In the absence of amyloid, tau pathology shows a normal (Gaussian) distribution between CA1 and CA2. These tau pathology distributions at younger ages are similar to the patterns seen at older ages in AD and PART.},
}

@article {pmid42024081,
year = {2026},
author = {Song, JH and Kim, HJ and Son, M and Kim, HR and Kim, SH and Kim, HS},
title = {The association between hemoglobin level and risk of developing dementia.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261443702},
doi = {10.1177/13872877261443702},
pmid = {42024081},
issn = {1875-8908},
abstract = {BackgroundHemoglobin levels are key indicators of health and may be associated with dementia risk. This study examined this association in a Korean population, stratified by sex.ObjectiveThis study aimed to evaluate the association between hemoglobin levels and the incidence of all-cause and subtype-specific dementia in a nationwide Korean cohort and to determine whether these associations differed by sex.MethodsFrom the National Health Insurance Service-National Health Screening Cohort, 316,542 adults aged ≥40 years were followed from 2004-2005 until 2019. Hemoglobin levels were divided into sex-specific quintiles. Dementia was defined by International Classification of Diseases, 10th Revision codes and prescriptions for anti-dementia medications. Risks of all-cause, Alzheimer's, and vascular dementia were analyzed using Cox proportional hazards models.ResultsCompared to the reference group (4th quintile), both the lower and higher hemoglobin quintiles were associated with an increased all-cause dementia risk (adjusted HR 1.16 [95% CI, 1.11-1.22] for Q1 and 1.07 [95% CI, 1.02-1.13] for Q5). Alzheimer's risk rose only in the lower quintiles, while vascular dementia risk rose at both extremes. These associations were stronger in women.ConclusionsAbnormal hemoglobin levels, particularly in women, were linked to an increased risk of dementia. Managing hemoglobin levels and correcting anemia may help prevent dementia.},
}

@article {pmid42024083,
year = {2026},
author = {Ye, Z and Zai, A and Wang, B and Bennett, A and Guilarte-Walker, YG and Wong, K and Zai, AH and Erban, S and Lin, H},
title = {Leveraging routine clinical data for dementia risk prediction using machine learning.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261443945},
doi = {10.1177/13872877261443945},
pmid = {42024083},
issn = {1875-8908},
abstract = {BackgroundEarly diagnosis of dementia is essential for enabling timely interventions that may slow disease progression, improve patient outcomes, and reduce healthcare costs. This study aims to develop machine learning models to predict dementia risk using longitudinal electronic health record (EHR) data.ObjectiveThis research aims to develop and evaluate machine learning models for dementia risk prediction using longitudinal EHR data from routine clinical care and to identify key clinical features associated with elevated dementia risks.MethodsWe conducted an incidence-based case-control study using EHR data from the UMass Memorial Health system (2017-2024) to develop a dementia risk prediction model.ResultsThis study included 5622 dementia cases and 44,976 controls. The XGBoost model achieved the highest AUC (0.802), with top predictors included thyroid-stimulating hormone (TSH), vitamin B12, and HDL cholesterol. Model performance was consistent across sexes and remained robust in multiple sensitivity analyses.ConclusionsMachine learning models that integrate comorbid conditions and longitudinal laboratory test patterns show their potential in predicting dementia risk. These findings highlight the promise of routinely collected EHR data as a scalable, low-cost resource for identifying individuals at elevated risk for dementia.},
}

@article {pmid42024084,
year = {2026},
author = {Xie, M and Niu, X and Sun, F and Shi, L},
title = {Transcriptome-based identification and experimental validation of a key gene in Alzheimer's disease using dermal fibroblasts.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261443968},
doi = {10.1177/13872877261443968},
pmid = {42024084},
issn = {1875-8908},
abstract = {BackgroundAlzheimer's disease (AD) is a neurodegenerative disorder primarily characterized by progressive cognitive impairment and neuronal damage. The pathogenesis of AD is complex and involves multiple pathological processes. Currently, effective methods for early diagnosis and treatment are lacking.ObjectiveTo identify key pathogenic genes and investigate their roles in Alzheimer's disease, we analyzed transcriptomic data from dermal fibroblasts of AD patients, aiming to assess their potential as novel biomarkers and therapeutic targets.MethodsTranscriptomic data from AD patient and control-derived dermal fibroblasts (DFs) were analyzed to identify differentially expressed genes. Key genes were screened using bioinformatics and a random forest algorithm. ceRNA analysis was performed to explore miRNA-mRNA interactions. The candidate gene SRSF5 was validated via overexpression and knockdown, followed by qPCR, western blotting, and reactive oxygen species (ROS) assays. The role of SRSF5 in endoplasmic reticulum (ER) stress was evaluated by measuring ER stress markers and cellular stress responses.ResultsTranscriptomic analysis revealed significant upregulation of SRSF5 in AD DFs. ceRNA analysis identified miRNAs regulating SRSF5 in AD. Overexpression of SRSF5 led to reduced neuronal proliferation, increased apoptosis, elevated ROS levels, and activation of ER stress markers (CHOP, GRP78, XBP1). SRSF5 knockdown alleviated these effects.ConclusionsSRSF5 may drive AD pathogenesis via ER and oxidative stress, serving as a potential biomarker and therapeutic target for early diagnosis and intervention.},
}

@article {pmid42024087,
year = {2026},
author = {Peck, MR and Chapman, JE and Hill, T and Quinn, K and Ikiz, ED and Lopez, A and Hascup, ER and Bae, C and Hascup, KN},
title = {D-methionine improves spatial navigation and attenuates oxidative stress and amyloid pathology in a sex-specific manner.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261444307},
doi = {10.1177/13872877261444307},
pmid = {42024087},
issn = {1875-8908},
abstract = {BackgroundOxidative stress and maladaptive neuroimmune activation contribute to cognitive decline in Alzheimer's disease (AD) and represent therapeutic targets beyond amyloid-centered approaches.ObjectiveTo determine whether oral D-methionine (D-Met), a redox-active amino acid, reduces amyloid pathology and lipid peroxidation and confers disease-modifying benefits in AD models.MethodsMale and female APP/PS1 and APP[NL-F] mice with advanced AD pathology received oral D-Met or vehicle. Behavioral assessments included locomotor activity and hippocampal-dependent spatial learning and memory. Amyloid burden, lipid peroxidation, peripheral metabolic, and inflammatory markers, and hippocampal microglial phenotypes were evaluated.ResultsD-Met did not alter locomotor or exploratory behavior but improved spatial memory recall in both sexes of APP/PS1 mice and in female APP[NL-F] mice. APP[NL-F] males exhibited improved Morris water maze learning. Amyloid pathology was region-specifically reduced, including decreased hippocampal plaque size in male APP[NL-F] mice, reduced cortical plaque size in female APP/PS1 mice, and lower soluble amyloid-β (Aβ)42 in male APP/PS1 mice. Lipid peroxidation was reduced only in female APP[NL-F] mice. D-Met induced pronounced sex-dependent peripheral effects, increasing adiposity and pro-inflammatory adipose signaling in males, while reducing perigonadal white adipose tissue IL-6 expression in female APP[NL-F] mice. In the hippocampus, D-Met decreased microglial activation, with female APP[NL-F] mice showing reduced Iba1 and disease-associated microglial markers and increased Axl expression.ConclusionsShort-term D-Met acts as a metabolic and redox modulator with amyloid-lowering effects mediated by improved microglial function. Therapeutic efficacy is strongly sex- and model-dependent, with the greatest benefit observed in female APP[NL-F] mice.},
}

@article {pmid42024089,
year = {2026},
author = {Lazaar, N and Rirash, AF and Papma, JM and Mattace Raso, FUS and Franzen, S},
title = {Beliefs, barriers, and behaviors: Exploring dementia prevention perspectives in culturally diverse populations in The Netherlands.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261443983},
doi = {10.1177/13872877261443983},
pmid = {42024089},
issn = {1875-8908},
abstract = {BackgroundModifiable risk factors play a key role in preventing or delaying dementia, yet little is known about how culturally diverse populations in Europe perceive these risk factors.ObjectiveThis study aimed to: (1) explore lay perceptions of dementia and its risk factors, and (2) examine how these perceptions interact with social and structural determinants of health to shape dementia prevention behaviors.MethodsWe conducted a qualitative study guided by the I-Change model, using semi-structured interviews with 20 adults varying in cultural and linguistic background, education, and age. Interviews were conducted in Dutch, English, and Moroccan-Arabic (Darija), translated if needed and transcribed verbatim. Data analysis followed open, axial, and selective coding to identify themes.ResultsParticipants emphasized genetics and biological vulnerability over modifiable risk factors when discussing dementia risk. Socioeconomic status, physical ability, and (social) environment were perceived to shape opportunities for healthy aging. Peers, family, and cultural norms were both facilitators and barriers to health-promoting behaviors. Lived- and observed experiences of illness motivated general behavior change, not specifically linked to dementia and Alzheimer's disease. Stress, sleep, resilience, and discipline were viewed as influential for cognitive health. Participants often integrated personal, cultural, and social perspectives when interpreting dementia risk.ConclusionsPerceptions of dementia and Alzheimer's disease risk among culturally diverse individuals are shaped by biological beliefs, psychosocial influences, and social context. Knowledge of dementia and modifiable risk factors remains limited among minoritized populations. Public health initiatives might benefit from incorporating prevention messages in a community perspective to enhance engagement and motivation.},
}

@article {pmid42024093,
year = {2026},
author = {Levine, TF and Mashinchi, GM and Rodrigues, J and Cross, CL and Caldwell, JZK and , },
title = {Effect of sex on trajectories of verbal learning and memory and clinical symptoms in diverse Alzheimer's disease cohorts.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261444759},
doi = {10.1177/13872877261444759},
pmid = {42024093},
issn = {1875-8908},
abstract = {BackgroundWomen continue to demonstrate a verbal learning and memory advantage compared to men even in the earliest stages of Alzheimer's disease (AD). However, the literature on sex differences in longitudinal AD trajectories is sparse, particularly in ethnically diverse samples.ObjectiveTo examine sex differences in verbal learning and memory, as well as clinical symptoms, in clinically normal non-Hispanic white (NHW) and Hispanic/Latino (HL) cohorts longitudinally.MethodsWe examined longitudinal sex effects on verbal learning and memory (Spanish-English Verbal Learning Test) and clinical symptoms (Clinical Dementia Rating Scale-Sum of Boxes) in NHW (n = 529) and HL (n = 439) participants with available AD biomarkers (plasma Aβ42/Aβ40 and hippocampal volume) who were clinically normal at baseline and completed follow-up assessment 18-24 months later.ResultsIn both cohorts, women demonstrated higher verbal learning and memory scores at baseline (ps < 0.001). In the NHW cohort, longitudinal sex differences were observed in verbal learning and memory, with women maintaining performance over time, whereas men's performance declined (p = 0.071 and p = 0.020, respectively). In the HL cohort, longitudinal sex differences were observed in clinical symptoms, with men demonstrating greater decline than women (p = 0.033). Trajectories of decline did not significantly differ between ethnic cohorts. AD biomarkers did not moderate observed effects.ConclusionsThis study highlights the potential impact of ethnicity on sex-based differences in cognitive decline in older adulthood. Future work is needed to determine best practices for tracking progression along the AD continuum, particularly within the preclinical phase.},
}

@article {pmid42024094,
year = {2026},
author = {Ye, Z and Teng, B and Wang, S and Zhu, J and Chen, J and Zhang, B and Cai, H and Wei, R and Li, B and Xie, X and Yu, X and Li, J and Huang, S and Weng, Y and Yang, D and , },
title = {Association of inflammation-related plasma proteins with vascular cognitive burden and Alzheimer's disease: A multi-method study.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261443713},
doi = {10.1177/13872877261443713},
pmid = {42024094},
issn = {1875-8908},
abstract = {BackgroundInflammation is implicated in the pathogenesis of dementia. However, its role in the vascular cognitive burden and the clinical stage of Alzheimer's disease (AD) remains controversial.ObjectiveThis study aimed to explore the association of plasma inflammatory proteins with vascular cognitive burden and clinical stage of AD by using a multi-method approach.MethodsWe included 330 individuals with complete plasma protein profiles, Hachinski Ischemia Scale scores, and cognitive function status between September 13, 2005, and October 24, 2007. We employed generalized linear models, restricted cubic splines, and the inverse variance weighting (IVW) method for two-sample Mendelian randomization (MR) to investigate the correlation between inflammatory biomarkers and dementia. We employed the random forest algorithm to build predictive models and utilized SHapley Additive exPlanations (SHAP) analysis for feature importance and interpretability.ResultsAD clinical stage exhibited significant associations with cortisol, C-peptide, tumor necrosis factor receptor-2 (TNFR-2) and interleukin-16 (IL-16, all p < 0.05). Similarly, the vascular cognitive burden was significantly correlated with C-peptide, carcinoembryonic antigen and TNFR-2 (all p < 0.05). These observational findings were corroborated by SHAP analysis. Subsequent MR analysis further revealed a weak negative causal relationship between AD and IL-16 (pIVW = 0.003; ORIVW = 0.981; 95% CI: 0.969-0.994).ConclusionsOur study identified several inflammatory proteins correlated with the vascular cognitive burden and AD clinical stage, providing exploratory evidence for future mechanistic and interventional research.},
}

@article {pmid42024095,
year = {2026},
author = {Kermel-Schiffman, I and Lifshitz, R and Carmel, S and Bachner, YG},
title = {Attitudes of older adults toward active euthanasia in advanced Alzheimer's disease.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261444353},
doi = {10.1177/13872877261444353},
pmid = {42024095},
issn = {1875-8908},
abstract = {BackgroundActive euthanasia by physicians involves administering a substance that directly causes a patient's death. In Alzheimer's disease, progressive cognitive decline and increasing dependence raise complex ethical and emotional dilemmas. Although legalized in some countries, active euthanasia remains controversial, with public attitudes shaped by multiple factors, particularly in advanced disease stages.ObjectiveThis study examined older adults' attitudes toward active euthanasia in advanced Alzheimer's disease from three perspectives: toward themselves, a family member, and an unknown individual. It also explored associations between sociodemographic and psychosocial variables and these attitudes.MethodsA quantitative study was conducted with 501 individuals aged 75+, recruited through day centers and snowball sampling. Attitudes were measured using hypothetical cases involving euthanasia decisions for oneself, a family member, and an unknown individual. Variables included self-efficacy, will to live, desire to prolong life, life satisfaction, fear of death, social support, and sociodemographic characteristics. Analyses employed mean comparisons and hierarchical linear regression models.ResultsParticipants reported the most favorable attitudes toward euthanasia when considering themselves (M = 3.61), followed by a family member (M = 3.22), with the least favorable attitudes expressed toward an unknown individual (M = 2.86). Lower desire to prolong life and higher self-efficacy predicted more positive attitudes across all cases, while lower will to live was positively associated only in personal and familial contexts. Female gender, higher education, and lower religiosity were linked to more favorable attitudes across all contexts.ConclusionsSociodemographic and personality characteristics should be considered when developing strategies aimed at increasing public awareness of active euthanasia, especially among older adults.},
}

@article {pmid42024098,
year = {2026},
author = {Pizzoni, L and Piero, AD and Blasutto, B and Casagrande, M and Piccardi, L and Guariglia, C},
title = {Accelerated long-term forgetting in Alzheimer's disease continuum: A systematic review and meta-analysis.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261443537},
doi = {10.1177/13872877261443537},
pmid = {42024098},
issn = {1875-8908},
abstract = {BackgroundAccelerated long-term forgetting (ALF), the disproportionate loss of information over days or weeks despite normal performance at standard delays, has been proposed as an early cognitive marker of Alzheimer's disease (AD).ObjectiveProvide a qualitative and quantitative synthesis of current evidence on ALF across the AD continuum.MethodsWe performed a systematic review and meta-analysis following the PRISMA 2020 guidelines. Eligible studies evaluated episodic memory with delays of at least 1 h in participants across the AD continuum compared to healthy controls. Risk of bias was assessed using the Joanna Briggs Institute (JBI) tools, and pooled effect sizes (Hedges' g) were calculated for delays of 1 day, 1 week, and 1 month or longer.ResultsTwenty-eight studies (n = 1399) were included; 16 entered quantitative analyses. The 1-day effect was nonsignificant (g = 0.55, 95% CI -0.03-1.12). At 1 week, ALF effect was robust (g = 0.63, 95% CI 0.40-0.87; I[2] = 0%) and evident in at-risk groups (g = 0.61, 95% CI 0.37-0.86) despite intact early retention. Both verbal (g = 0.74) and non-verbal (g = 0.53) tasks, as well as recall (g = 0.61) and recognition (g = 0.70), showed similar sensitivity. Effects persisted at ≥1 month but weakened in at-risk groups.ConclusionsALF is strongly detected in the preclinical stage of AD, especially at a 1-week delay across different materials and retrieval methods. Long-delay memory tests may enhance the sensitivity of neuropsychological assessments for detecting early cognitive issues in the early stages of the AD continuum.},
}

@article {pmid42024099,
year = {2026},
author = {Phan, ALG and Beare, R and Ma, H and Srikanth, V and Phan, TG},
title = {Mapping hotspots of self-reported dementia and memory clinics across Australia.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261444254},
doi = {10.1177/13872877261444254},
pmid = {42024099},
issn = {1875-8908},
abstract = {BackgroundDementia prevalence is increasing in Australia. It is unknown whether there are hotspots for dementia in metropolitan or non-metropolitan areas. This knowledge is important for healthcare planning.ObjectiveThis paper will examine where hotspots for self-reported dementia in Australia are, and whether they are adequately serviced by multidisciplinary memory clinics.MethodsWe used self-reported dementia data from the 2021 Australian Census at the local government area (LGA) level. LGAs represent public administrative regions within Australian states and territories. Standardized prevalence ratios (SPR) were calculated for each LGA by dividing the number of self-reported cases by the expected number of cases. Spatial relationships were investigated with Bayesian spatial regression using integrated nested Laplace approximations. Memory clinics were located using Australian Dementia Network and government websites.ResultsSelf-reported dementia prevalence was lower in metropolitan areas (72.3 per 10,000) compared to non-metropolitan areas (79.9 per 10,000). There are 108 multidisciplinary memory clinics in Australia, 83 of which are metropolitan. Hotspots for self-reported dementia occurred in non-metropolitan east coast of New South Wales (SPR: 2.13), southeast Queensland (SPR: 1.72), and northwest of greater city Adelaide (SPR: 2.55). LGAs in major cities had lower SPRs (Melbourne: 0.40; Sydney: 0.45), apart from Western Adelaide (SPR: 1.88).ConclusionsHotspots for self-reported dementia were mainly in non-metropolitan Australia, whereas memory clinic services were mostly in metropolitan areas, raising issues of equity and access to services.},
}

@article {pmid42024100,
year = {2026},
author = {Peloso, GM and Wang, D and Abbruzzese, SM and Bis, JC and Choi, SH and Beiser, A and Bressler, J and Dupuis, J and Fohner, AE and Ghanbari, M and Gibbs, RA and Heard-Costa, N and Ikram, MA and Lacaze, P and Le Grand, Q and Lopez, OL and Mosley, TH and Riaz, M and Soumaré, A and Yaqub, A and Boerwinkle, E and Psaty, BM and Fornage, M and , and Seshadri, S and DeStefano, AL},
title = {Whole genome sequencing analysis of over 3500 individuals dementia-free over 85 years old.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261444302},
doi = {10.1177/13872877261444302},
pmid = {42024100},
issn = {1875-8908},
abstract = {BackgroundIdentifying genetic variants conferring resilience to Alzheimer's disease and related dementia (ADRD) may hold promise for developing therapeutics.ObjectiveTo determine genetic associations with being dementia-free at age 85 (DF85).MethodsWe examined genetic associations, using whole genome sequencing data, with DF85 in three Trans-Omics for Precision Medicine cohorts and the Alzheimer's Disease Sequencing Project Phenotype Harmonization Consortium. We tested common variants individually and aggregation of rare (MAF ≤ 1%) coding and non-coding variants in DF85 participants (n = 3657) against individuals who were not DF85 (n = 20,010). We verified associations using a stricter control set who developed dementia before age 85 (n = 5552).ResultsWe observed an association at APOE (rs429358, MAF = 0.21, odds ratio [OR] = 0.49, 95% confidence interval [CI] = 0.46-0.53, p = 1.0 × 10[-92]) as well as for two common variants (rs16892237-A near MAL2, MAF = 0.08, OR = 1.34, 95% CI = 1.21-1.48, p = 1.1 × 10[-8] and rs8004018-G near GCH1, MAF = 0.16, OR = 1.24, 95% CI = 1.15-1.34, p = 1.7 × 10[-9]) and an aggregate of rare loss of function and disruptive missense variants in FBXW10 on chr 17 (p = 1.4 × 10[-7]) associated with DF85.ConclusionsThrough a genome-wide assessment of a resilience-focused outcome, we identified common and rare genetic variants contributing to DF85 status. Genes associated with DF85 may delay onset of ADRD and provide translational impact.},
}

@article {pmid42024102,
year = {2026},
author = {Agavriloaei, LM and Costachescu, I and Szilagyi, A and Gogu, MR and Iliescu, BF and Turliuc, MD},
title = {How amyloid-β peptide choice shapes neurochemical outcomes in intracerebral rat models of Alzheimer's disease: A systematic review.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261443555},
doi = {10.1177/13872877261443555},
pmid = {42024102},
issn = {1875-8908},
abstract = {BackgroundIntracerebral administration of amyloid-β (Aβ) peptides remains a widely used experimental approach for modeling key neurochemical features of Alzheimer's disease (AD), including neuroinflammation, oxidative stress, and synaptic dysfunction. Among these models, Aβ1-42 and Aβ1-40 are most frequently employed. However, their effects are often treated as interchangeable despite recognized differences in aggregation behavior and biological activity.ObjectiveThis systematic review aimed to synthesize evidence on how peptide selection between Aβ1-42 and Aβ1-40 shapes neurochemical outcomes in intracerebral rat models of AD.MethodsThe review was conducted in accordance with PRISMA guidelines and registered in PROSPERO. A structured search identified in vivo rat studies using Aβ1-42 or Aβ1-40. Given methodological heterogeneity, findings were synthesized using a qualitative framework. To address potential structural confounding, stratified analyses were performed according to injection route and aggregation state.ResultsEighty-three studies met inclusion criteria (Aβ1-42 = 60; Aβ1-40 = 23). Across neurochemical domains, Aβ1-42 was more frequently associated with earlier and glial activation, increased pro-inflammatory mediators, oxidative imbalance, and synaptic alterations, often accompanied by behavioral deficits. In contrast, Aβ1-40 models showed a more variable and generally attenuated neurochemical response with greater dependence on experimental parameters. Structural analyses indicated clustering by injection route, whereas aggregation-state distribution was not statistically skewed between peptides.ConclusionsThe available evidence suggests that Aβ1-42 and Aβ1-40 should not be assumed interchangeable without explicit methodological consideration. Observed differences appear context-dependent and influenced by experimental design variables. Peptide selection with defined mechanistic objectives may enhance interpretability and translational relevance in preclinical AD research.},
}

@article {pmid42024105,
year = {2026},
author = {Smith, AN and Burns, JM and Sullivan, DK and Morris, JK and Carbuhn, AF and Herda, TJ and Thyfault, JP and Taylor, MK},
title = {Larger baseline body stature predicts one-year amyloid change in cognitively normal older adults enriched with elevated amyloid status.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261445598},
doi = {10.1177/13872877261445598},
pmid = {42024105},
issn = {1875-8908},
abstract = {BackgroundRising Alzheimer's disease (AD) incidence underscores the need to identify modifiable risk factors. The "obesity paradox" suggests higher late-life body mass index (BMI) may reduce AD risk. Because BMI does not distinguish between fat and lean mass, investigating body composition and brain amyloid accumulation may clarify this relationship.ObjectiveThis study tested whether baseline body stature predicts one-year change in brain amyloid.MethodsUsing data from the Alzheimer's Prevention through Exercise trial, we examined whether baseline body stature and composition (BMI, fat mass index [FMI], lean mass index [LMI], and total fat and lean mass) predicted one-year change in brain amyloid among 106 cognitively healthy older adults enriched with elevated amyloid status.ResultsHigher baseline BMI predicted less one-year amyloid accumulation globally (β = -0.33, p = 0.001) and in five of six brain regions (p = 0.001-0.05). Higher FMI predicted less amyloid accumulation globally (β = -0.35, p < 0.001) and in all six regions (p < 0.001-0.02), while higher LMI predicted less accumulation globally and in four regions (p < 0.001-0.02). Higher total fat mass was associated with less amyloid globally and regionally (p < 0.001-0.02), whereas higher total lean mass predicted reduced accumulation only in the lateral temporal lobe (p = 0.01).ConclusionsLarger body mass predicted less amyloid accumulation in cognitively healthy older adults over one year. More research is needed to investigate whether larger body stature protects against amyloid accumulation and explore underlying mechanisms.Clinical Trial RegistrationClinicalTrials.gov, Identifier (NCT02000583).},
}

@article {pmid42024106,
year = {2026},
author = {Toccaceli Blasi, M and Salzillo, M and Buscarnera, S and Nuti, F and Stanziale, C and Pecorari, C and Ottone, DA and Salati, E and D'Antonio, F and Canevelli, M and Bruno, G},
title = {A diary-based approach to improve neuropsychiatric symptom assessment in dementia: A cross-sectional comparison with the neuropsychiatric inventory.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261443922},
doi = {10.1177/13872877261443922},
pmid = {42024106},
issn = {1875-8908},
abstract = {BackgroundNeuropsychiatric symptoms (NPS) are among the most challenging manifestations of dementia. Currently available assessment tools often fail to fully capture their complexity. Thus, novel approaches are needed.ObjectiveThe present study aimed to explore the application of a diary-based assessment of NPS in patients with dementia attending a memory clinic and compare this novel approach with the Neuropsychiatric Inventory (NPI) in terms of scores, time efficiency, and influence of potential confounders.MethodsAll consecutive outpatients with dementia and NPS attending the Center for Cognitive Disorders and Dementia, Sapienza University of Rome, were considered for enrollment. Caregivers completed a specially designed NPS diary for one month. Subsequently, a standard NPI (sNPI) was administered, and two diary-based NPIs (dNPI-R1 and dNPI-R2) were independently reconstructed by trained raters. Scores were compared using repeated-measures ANOVA and Cochran's Q test. Multivariate regression models were conducted to examine the impact of covariates. In addition, the NPS diary was qualitatively analyzed, and caregivers provided structured feedback.ResultsForty patient-caregiver dyads completed the study procedures. The sNPI yielded higher scores and longer administration time than dNPIs. Diary-based assessments showed high inter-rater reliability and were less influenced by caregiver burden.ConclusionsThe NPS diary offered an ecological, caregiver stress-resistant, reliable, time-efficient, and feasible evaluation of NPS. It allowed a detailed description of NPS, including temporal fluctuations, triggers, and resolution strategies. Integration of this complementary modality with standard evaluations allows a more comprehensive assessment of NPS in dementia.},
}

@article {pmid42024107,
year = {2026},
author = {López-Carbonero, JI and Peña-de Diego, L and Valles-Salgado, M and Delgado-Álvarez, A and Delgado-Alonso, C and Fernández-Romero, L and Barroso, Y and Gil-Moreno, MJ and Sánchez-Benavides, G and Peña-Casanova, J and Matías-Guiu, JA},
title = {Cognitive characterization of the behavioral variant of frontotemporal dementia using the Neuronorma battery.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261443917},
doi = {10.1177/13872877261443917},
pmid = {42024107},
issn = {1875-8908},
abstract = {BackgroundFrontotemporal dementia (FTD) is a neurodegenerative disorder characterized by progressive behavioral changes, executive dysfunction, and language impairment. The behavioral variant (bvFTD) is the most common form and often overlaps clinically with psychiatric disorders and Alzheimer's disease (AD), complicating early diagnosis. Neuropsychological assessment is therefore essential, yet standardized tools for bvFTD are limited.ObjectiveThis study aimed to characterize the cognitive profiles of bvFTD across prodromal and demented stages using the Neuronorma neuropsychological battery.MethodsWe analyzed clinical and neuropsychological data from 122 bvFTD patients, including 35 prodromal (Clinical Dementia Rating (CDR) 0.5) and 87 demented (CDR>0.5) cases. Cognitive domains assessed were attention, executive function, memory, verbal fluency, naming, and visuospatial abilities, with impairment defined using two Z-score thresholds (≤ -1 and ≤ -1.67). Patient performance was compared to age-, sex-, and education-matched healthy controls.ResultsWe found frequent deficits in executive function, semantic fluency, verbal and visual memory, and visuospatial abilities, even among prodromal patients. Multi-domain impairment predominated in demented cases, whereas prodromal profiles were heterogeneous, occasionally presenting isolated memory deficits. Comparison with matched controls confirmed significant differences across most tests, with large effect sizes in memory, executive function, attention, and verbal fluency.ConclusionsThese findings support the use of the Neuronorma battery for the cognitive assessment of bvFTD, from the prodromal stages. Furthermore, the presence of non-executive cognitive deficits in bvFTD highlights the need for comprehensive cognitive profiling in differential diagnosis.},
}

@article {pmid42024109,
year = {2026},
author = {Libon, DJ and Bazzano, LA and Woo, JG and Price, CC and Anda-Duran, I and Chapin, B and Urbina, EM and Baliga, G},
title = {Defining neurocognitive constructs underlying visual attention in mild cognitive impairment and dementia using digital assessment technology.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261441636},
doi = {10.1177/13872877261441636},
pmid = {42024109},
issn = {1875-8908},
abstract = {BackgroundProblems with visual attention can be an early indication for the emergence of dementia.ObjectiveThe current research assessed visual attention using three iPad administered, digital cancellation tests.MethodsLetter and Symbol Cancellation Tests asked participants to circle a specific letter or symbol. On the Mixed Cancellation Test, participants alternated circling a letter, then a symbol. Five outcome variables were tallied: correct hits; mean intra-response pause or "think" time; mean drawing or "ink" time to circle correct hits; mean distance or search between correct targets; and commission errors. All but commission errors were expressed in four cumulative time epochs; 0-30 s, 0-60 s, 0-90 s, and 0-120 s. Using a protocol of paper/ pencil neuropsychological tests, Jak, Bondi criteria were used to classify 145 memory clinic patients into groups suggesting normal cognitive abilities (CL; n = 45); subtle or mild cognitive impairment (MCI; n = 62); and mild dementia (DEM; n = 38).ResultsFor correct hits and mean pause/ "think" time, the three groups were dissociated from each other at 60, 90, and 120 s. For mean drawing/'ink' time far fewer between-group differences were found. There was no difference across the three tests for mean search. On the Symbol and Mixed Cancellation Tests, MCI and DEM patients produced more commission errors than CL participants.ConclusionsFaster pause or "think time", perhaps reflecting better disengagement from circling target items, may underlie better cancellation test performance. When brought to scale, The Rowan Cancellation Tests could be an effective means to screen for MCI and emergent dementia.},
}

@article {pmid42024112,
year = {2026},
author = {Tan, S and Markaryan, M and Ribeiro, Ó and Branco, RM and Sousa, L},
title = {Unmet social needs of community-living older adults with dementia: A scoping review.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261442966},
doi = {10.1177/13872877261442966},
pmid = {42024112},
issn = {1875-8908},
abstract = {Dementia-related cognitive decline and ageing-related challenges impact social participation and relationships. Limited knowledge of dementia among family, friends and the public hinder support for interactions with those affected. Unmet social needs in community-living older adults with dementia remain underrecognized, despite their importance in healthy ageing and quality of life. This scoping review mapped existing evidence on unmet social needs of community-living older adults with dementia, including how these needs vary across dementia stages. We conducted a scoping review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) and Joanna Briggs Institute (JBI) guidelines. Four databases were searched (2000 -April 2025) in English, Portuguese and Mandarin, yielding 24 included articles. Seven themes of unmet social needs were identified: (i) participation in out-of-home activities, (ii) support for maintaining independence in daily life (iii) companionship, (iv) meaningful relationships, (v) respectful and dignified social interactions, (vi) emotional support, and (vii) social needs during the pandemic. Unmet social needs differed by dementia stage: in mild dementia, unmet social needs mostly relate to out-of-home activities, while in moderate and severe stages unmet social needs shifted towards daily activities, companionship and emotional support. Stigma emerged as a transversal influence shaping experiences of unmet social need across stages and contexts. Unmet social needs evolve across dementia stages and are influenced by relational, socio-cultural and structural factors. Future research should include more advanced stages, diverse populations, and strategies for addressing social needs from their own perspectives.},
}

@article {pmid42024113,
year = {2026},
author = {Kim, S and Cho, B},
title = {Weight instability and risk of incident dementia among older stroke survivors: A nationwide cohort study.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261445058},
doi = {10.1177/13872877261445058},
pmid = {42024113},
issn = {1875-8908},
abstract = {BackgroundWeight loss, weight gain, and body mass index (BMI) instability have been linked to dementia risk in older adults. Stroke survivors may be particularly vulnerable to accelerated cognitive decline due to impaired physiological reserve and nutrition-related challenges. However, evidence on BMI change and dementia in this high-risk population remains limited.ObjectiveTo investigate the association between annual BMI change and incident dementia in a nationwide cohort of older stroke survivors.MethodsUsing KNHIS data, we identified adults aged ≥65 years with a history of stroke who underwent repeated health examinations. Annual BMI change was categorized as decreased (≤-1 kg/m[2]/year), stable (-1 to <1), or increased (≥1). Incident dementia (2013-2022) was defined using ICD-10 diagnostic codes combined with anti-dementia medication prescriptions. Multivariable Cox proportional hazards models and stratified analyses were conducted.ResultsAmong 26,174 older stroke survivors, 6727 developed dementia over a mean follow-up of 5.40 ± 2.73 years. Compared with stable BMI, both BMI decrease (HR 1.19; 95% CI 1.13-1.26) and BMI increase (HR 1.13; 95% CI 1.06-1.20) were associated with elevated dementia risk. The association for BMI decrease was consistent across sex and baseline BMI strata, whereas the association for BMI increase was primarily observed in men and those with normal baseline BMI.ConclusionsBoth BMI decreases and increases were associated with elevated dementia risk, with BMI decline showing the most consistent associations across subgroups. These findings suggest that monitoring weight trajectories may help identify older stroke survivors at heightened dementia risk in routine clinical practice.},
}

@article {pmid42024116,
year = {2026},
author = {Chiu, WH and Kang, MJY and Goh, AMY and Velakoulis, D and Loi, SM},
title = {Systematic review and meta-analysis of associations between neuropsychiatric symptoms and amyloid, tau, neuronal, and glial biomarkers in young-onset dementias.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261443355},
doi = {10.1177/13872877261443355},
pmid = {42024116},
issn = {1875-8908},
abstract = {BackgroundNeuropsychiatric symptoms (NPS) are highly prevalent in dementia. While biomarkers reflecting amyloid, tau, neuronal injury, and glial activation are increasingly used in dementia research, their association with NPS remains unclear.ObjectiveTo identify and characterise associations between biomarkers and NPS in people with young-onset dementia (YOD).MethodsWe conducted a systematic review and meta-analysis of studies examining associations between validated biomarkers and NPS in individuals with Alzheimer's disease (AD), frontotemporal dementia (FTD), Huntington's disease (HD), and vascular dementia (VaD), published between 2010 and 2024. The review followed PRISMA guidelines and was prospectively registered (PROSPERO; CRD42022314243).ResultsPrinciple meta-analyses identified no consistent evidence for associations between NPS and amyloid, tau, and neuronal biomarkers in AD, with limited data available for glial biomarkers. There was a scarcity of studies investigating the relationship between biomarkers and NPS in HD, VaD, and FTD.ConclusionsThe absence of consistent associations likely reflects substantial heterogeneity in pathology, clinical presentation, and methodological approaches, particularly within YOD populations, rather than a true lack of biological linkage. NPS in dementia may emerge from complex bio-psycho-social interactions that transcend classical biomarker models. Longitudinal, multimodal studies are needed to better delineate these relationships.},
}

@article {pmid42024117,
year = {2026},
author = {Santos, LTR and Costa, FL and Rosa, ID and Frota, AF and Bezerra, JR and Soares, MVR and Barbosa, CSN and Farias, JWF and da Silva, LRAM and Gonçalves, PVS and Carvalho, LEM and Carlos, LMB and Coelho Filho, JM and Lôbo, RR and Gallo, MBC and Teixeira, AL and Diniz, BS and Peixoto Junior, AA and Macedo, DS},
title = {A metabolic-glial plasma signature defines early Alzheimer's disease: Insights from an understudied cohort.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261441581},
doi = {10.1177/13872877261441581},
pmid = {42024117},
issn = {1875-8908},
abstract = {BackgroundEarly detection and staging of Alzheimer's disease (AD) remain challenging in low-resource settings where cerebrospinal fluid analysis and neuroimaging are not routinely accessible. Blood-based biomarkers such as phosphorylated tau at threonine 181 (p-tau181), glial fibrillary acidic protein (GFAP), and amyloid-tau ratios have improved diagnostic performance; however, their integration with systemic metabolic markers remains insufficiently investigated.ObjectiveTo characterize metabolic-neuroglial plasma signatures across the cognitive continuum and identify biomarkers capable of discriminating mild cognitive impairment (MCI) from mild AD and cognitively unimpaired (CU) individuals.MethodsSeventy adults classified as CU, MCI, or mild AD underwent plasma quantification of Aβ40, Aβ42, p-tau181, and GFAP alongside metabolic markers, including glycated hemoglobin, calcium, vitamin D, homocysteine, thyroid-stimulating hormone, C-reactive protein, and platelet count. Group comparisons were conducted using non-parametric tests. Multivariate approaches, principal component analysis, partial least squares discriminant analysis, and Random Forest (RF), were applied to detect discriminative biomarker patterns, incorporating automatically generated ratios.ResultsMCI participants showed higher plasma homocysteine and Aβ40 than CU. Mild AD was characterized by elevated p-tau181 and GFAP and a reduced amyloid-tau balance captured by Aβ40-based ratios. CU was distinguishable from both clinical groups using univariate markers and ratios, whereas separation between MCI and mild AD required multivariate integration. A six-biomarker RF signature robustly discriminated MCI from mild AD (AUC = 0.854; permutation p = 0.0044).ConclusionsIntegrated plasma panels combining neurodegenerative and metabolic markers improve staging across the AD continuum and may support clinical decision-making where advanced diagnostics are limited.},
}

@article {pmid42024118,
year = {2026},
author = {Sun, Q and Li, Y and Wang, Y and Tao, SS and Huan, X and Li, YQ and Zhang, H},
title = {Dysbiosis of gut microbiota synergizes with the activation of enteric glial cells to promote Alzheimer's disease.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261441247},
doi = {10.1177/13872877261441247},
pmid = {42024118},
issn = {1875-8908},
abstract = {BackgroundThe microbiota-gut-brain axis (MGBA) plays a crucial role in the onset and progression of Alzheimer's disease (AD). Enteric glial cells (EGCs) represent a fundamental cellular constituent that upholds the structural and functional integrity of the MGBA. However, the specific mechanistic role of EGCs in the pathogenesis of AD remains unclear.ObjectiveThe present study aimed to investigate the synergistic interaction between gut microbiota (GM) dysbiosis and EGCs activation in a mouse of AD.MethodsAmyloid precursor protein (APP)/presenilin 1 (PS1) transgenic AD mice were utilized as the experimental model. Behavioral experiments, 16S rRNA sequencing, Nissl staining, and immunofluorescence staining were used to evaluate the related changes of AD in cognitive function, neuropathology, GM, and EGCs, respectively.ResultsAD mice exhibited significant cognitive dysfunction, with obvious neuronal damage and Aβ plaques formation in the hippocampus and primary somatosensory cortex. The GM composition of AD mice was significantly altered, α-diversity decreased, and the dominant bacterial population was significantly different from the control group. Morphologically, EGCs in the myenteric plexus (MP) and submucosal plexus (SP) of AD mice were markedly activated, concomitant with a reduction in neuronal count. This alteration in EGCs-neuron interactions was shown to be region-specific in MP and SP.ConclusionsThis study confirms characteristic alterations in GM and abnormal EGCs activation in AD mice, while also uncovering regional specificity of these changes within the enteric nervous system. These findings may provide experimental evidence for the development of targeted intervention strategies for AD based on GM and EGCs.},
}

@article {pmid42024119,
year = {2026},
author = {Shan, A and Xu, C and Chen, R and Han, X and Sun, W and Yao, Q and Wang, X and Luan, H and Li, S and Wen, B and Cui, T and Guo, J and Lian, Q and Sun, Y and Li, C and Jia, H and Ma, H and Lv, S and Sun, Q and Wei, C},
title = {Alterations in choroid plexus volume associated with butylphthalide treatment in mild cognitive impairment: Data from a randomized, placebo-controlled study.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261443718},
doi = {10.1177/13872877261443718},
pmid = {42024119},
issn = {1875-8908},
abstract = {BackgroundThe choroid plexus (ChP) is increasingly recognized as an essential component in the pathogenesis of cognitive impairment associated with Alzheimer's disease. DL-3-n-butylphthalide (NBP) has been confirmed to exert neuroprotective effects through multiple pathways and thereby enhance cognitive function. However, the role of NBP in the ChP volume remains unclear at present.ObjectiveThis trial aimed to explore the clinical efficacy of NBP in patients with mild cognitive impairment (MCI) and its corresponding ChP imaging characteristics.MethodsThis randomized, double-masked, placebo-controlled study included 270 MCI patients, randomly assigned in a 1:1 ratio to receive either NBP or placebo. Concurrently, all participants received clinical cognitive evaluations and 3D T1-weighted magnetic resonance imaging scans at both baseline and post-treatment phases. The objective was to evaluate the efficacy of 12-month NBP treatment on cognitive impairment and investigate the neuroimaging correlates of NBP therapy, focusing specifically on longitudinal alterations in ChP.ResultsThe NBP treatment significantly improved the cognitive symptoms of MCI patients, which was strongly correlated with the decrease in ChP volume in the drug group. Moreover, subgroup analysis indicated that cognitive enhancement was closely related to changes in ChP volume in the effective group. Mediation effect analysis revealed that ChP volume partially mediated the enhancement of cognitive symptoms in MCI patients undergoing NBP treatment.ConclusionsThis research provided evidence that NBP may improve cognitive symptoms in MCI patients by regulating changes in ChP volume, as well as offered insight into identifying early neuroimaging markers of MCI and drug targets for NBP.Clinical trial registry nameEfficacy and safety of butylphthalide on patients with mild cognitive impairment; Registration number: ChiCTR1800018362.},
}

@article {pmid42024130,
year = {2026},
author = {Kitagawa, K and Toi, S and Yoshizawa, H and Todo, K},
title = {Underweight is associated with increased risk of all-cause dementia in older adults with vascular risk factors, independent of brain atrophy and small vessel disease.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261443944},
doi = {10.1177/13872877261443944},
pmid = {42024130},
issn = {1875-8908},
abstract = {BackgroundUnderweight, defined as a body mass index (BMI) < 18.5 kg/m2, has been associated with increased risk of dementia in older adults. However, whether this association reflects a causal relationship remains unclear.ObjectiveTo examine the association between low BMI and dementia, independent of brain magnetic resonance imaging findings.MethodsWe analyzed data from patients aged ≥ 65 years with vascular risk factors enrolled in a Japanese observational registry. Patients were categorized by BMI as underweight (<18.5 kg/m[2]), normal weight (18.5-24.9 kg/m[2]), or overweight (≥25.0 kg/m[2]). The outcomes were all-cause dementia and Alzheimer's disease (AD) dementia.ResultsA total of 607 patients (median age, 74 years) were included: 58 underweight, 389 normal weight, and 160 overweight. During a median follow-up of 4.7 years, 39 patients developed dementia and 30 developed AD dementia. Kaplan-Meier analysis showed that underweight group had a significantly higher incidence of all-cause dementia (p = 0.002) and AD dementia (p = 0.009) compared with the other groups. Cox regression hazard analysis adjusted for age and sex revealed that underweight had a higher risk of all-cause dementia (hazard ratio, 3.38; 95% confidence interval, 1.49-7.67) compared with normal weight. In exploratory analysis, the association between underweight and all-cause dementia remained significant after adjustment for additional confounders, medial temporal atrophy, and white matter hyperintensities.ConclusionsUnderweight in older adults was associated with increased risk of all-cause dementia independent of age, sex, confounding factors, brain atrophy and white matter hyperintensities. These findings warrant confirmation in larger cohorts.Clinical Trial RegistrationUMIN000026671.},
}

@article {pmid42024235,
year = {2026},
author = {Alameen, AAM and Al-Kuraishy, HM and Fawzy, MN and Batiha, GE},
title = {Targeting the FOXO4-p53 axis by retro-inverso peptide senolytic agents: a pharmacological strategy to mitigate brain aging and cognitive decline.},
journal = {Naunyn-Schmiedeberg's archives of pharmacology},
volume = {},
number = {},
pages = {},
pmid = {42024235},
issn = {1432-1912},
abstract = {Cellular senescence, driven by the interaction between FOXO4 and p53, is increasingly recognized as a crucial mechanism in brain aging and the development of neurodegenerative disorders. The senolytic peptide FOXO4-DRI, which has been thoughtfully designed, selectively disrupts the FOXO4-p53 complex, inducing apoptosis in senescent cells while preserving healthy tissue. In aged mammalian models, administering FOXO4-DRI decreases the accumulation of senescent cells, restores cerebral blood flow and the integrity of the blood-brain barrier (BBB), reverses hippocampal atrophy, and enhances cognitive function. Furthermore, in models of Alzheimer's disease (AD) and tauopathy, this intervention eliminates amyloid-β and pathological tau, leading to improved memory performance. Preliminary human studies involving FOXO4-axis modulators, such as high-dose fisetin, show a reduction in the senescence-associated secretory phenotype (SASP) and enhancements in cognitive and physical measures among older adults. These findings collectively identify the FOXO4-p53 axis as a potential pharmacological target in brain aging and highlight senolytic therapy as a promising strategy for altering diseases to postpone or reverse age-related cognitive decline. This review consolidates recent findings indicating that FOXO4-dependent senescence significantly contributes to neuroinflammation, synaptic dysfunction, and impaired neurogenesis in the aging brain.},
}

@article {pmid42024241,
year = {2026},
author = {Alım, Z and Demir, Y},
title = {Evaluation of pyrimidine-based compounds as AChE and BChE inhibitors: in vitro inhibition, molecular modeling, and statistical evaluation.},
journal = {Naunyn-Schmiedeberg's archives of pharmacology},
volume = {},
number = {},
pages = {},
pmid = {42024241},
issn = {1432-1912},
abstract = {Alzheimer's disease (AD) is a neurodegenerative disease characterized by dementia, particularly in older adults. It is a process that is increasing significantly with the aging population worldwide, has yet to be cured, and therefore challenges healthcare systems. The ability of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors to modulate neurotransmitter levels has made AChE/BChE inhibitors central therapeutic targets in drug development studies for the treatment of AD. Previous studies have demonstrated the beneficial effects of pyrimidine derivatives on cognitive functions and highlighted their high therapeutic potential against neurodegenerative diseases. Considering the pharmacological importance of AChE/BChE inhibitors and pyrimidine derivatives, this study investigated the inhibitory potential of seven different pyrimidine derivatives (1-7) on AChE and BChE using both in vitro and in silico approaches. Analysis of IC50 values indicated that compounds 1-7 (IC50: 14.89-77.70 nM) exhibited strong inhibitory effect. Compound 6 (IC50:14.89 nM) had the strongest inhibitory effect on AChE, while it showed a much weaker inhibitory effect against BChE (IC50: 357 nM), corresponding to an approximately 24-fold selectivity for AChE. Molecular modeling results indicate that compounds 6 and 7 exhibit favorable interactions within the active site of the enzyme. In addition, compounds 1 and 3, which exhibited the strongest inhibitory effects on BChE, appear to display a multiple binding profile with the active site of BChE. Correlation and regression analyses indicated that compounds 1-7 display a structure-activity relationship (SAR) consistent with strong inhibitory potency toward AChE, while showing comparatively weaker inhibition toward BChE.},
}

@article {pmid42024278,
year = {2026},
author = {Ebrahimi, R and Mohammadi, I and Ghafourian, K and Rajai Firouzabadi, S and Saleh, M and Davoody, S and Azad, G and Esmaeilpour, K},
title = {The multifaceted role of mitochondrial dysfunction in Alzheimer's disease pathogenesis.},
journal = {Metabolic brain disease},
volume = {41},
number = {1},
pages = {},
pmid = {42024278},
issn = {1573-7365},
}

@article {pmid42024486,
year = {2026},
author = {Liu, X and Liu, J and Wang, PY and Cui, JH and Bu, YM and Wu, SS and Zhang, YH and Guo, C},
title = {Parthenolide Ameliorates Alzheimer's Disease Pathology by Suppressing Microglial Inflammation and Inflammation-Driven Amyloidogenesis via the HIF1α/NF-κB Axis.},
journal = {ACS chemical neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1021/acschemneuro.6c00141},
pmid = {42024486},
issn = {1948-7193},
abstract = {The treatment landscape for Alzheimer's disease (AD) faces challenges such as prolonged drug development, high costs, and limited FDA-approved therapies. Given the pathological similarities between Early-Onset AD (EOAD) and Late-Onset AD (LOAD), repurposing existing drugs offers a promising strategy to expedite therapeutic development. In this study, weighted gene coexpression network analysis (WGCNA) was applied to identify AD-associated gene modules, followed by network pharmacology to screen candidate compounds. Parthenolide was selected based on blood-brain barrier permeability and disease relevance. Its effects were evaluated using LPS-stimulated BV2 microglia, N2a-sw and HT22 neuronal models, and transgenic AD mouse models. Transcriptomic integration, transcription factor enrichment, pharmacological inhibition, and in vivo behavioral and pathological analyses were employed to elucidate underlying mechanisms. Our findings reveal that parthenolide markedly suppressed microglial activation and reduced pro-inflammatory mediators via modulation of the HIF1α/NF-κB signaling axis. Bioinformatics analysis identified HIF1α as a key hub gene, which was experimentally validated using the selective inhibitor YC-1. Parthenolide attenuated inflammation-induced amyloidogenesis by downregulating amyloid β precursor protein (APP) expression and the γ-secretase component Aph-1A γ-Secretase Subunit (APH1α). In vivo, parthenolide administration significantly improved cognitive performance, reduced microglial activation, decreased β-amyloid plaque burden, and suppressed HIF1α/NF-κB-dependent inflammatory signaling in 5 × FAD mouse models. In conclusion, this study demonstrates that parthenolide exerts multitarget therapeutic effects in AD by concurrently suppressing neuroinflammation and amyloidogenic processing. Targeting the HIF1α/NF-κB axis may represent a promising strategy for modulating inflammatory-metabolic-amyloid networks in AD.},
}

@article {pmid42024684,
year = {2026},
author = {Yasuda, SM and Mock, C and Gauthreaux, K and Chan, KCG and Keene, CD and Culhane, JE and Chen, YC and Kukull, W},
title = {Effects of concurrent neuropathologies with Alzheimer disease neuropathologic change on cognitive decline: Minimal impact of vascular brain injury compared with other combinations.},
journal = {Journal of neuropathology and experimental neurology},
volume = {},
number = {},
pages = {},
doi = {10.1093/jnen/nlag033},
pmid = {42024684},
issn = {1554-6578},
support = {U24 AG072122/AG/NIA NIH HHS/United States ; },
abstract = {We examined cognitive changes associated with several neuropathologic entities, alone and in combination. We studied 808 participants from the National Alzheimer's Coordinating Center to assess associations between neuropathologic diagnoses (from autopsy) and neuropsychologic test scores (trajectories over time for 5 domains: overall cognition, episodic memory, attention, language, executive function). Neuropathologies included: Alzheimer disease neuropathologic change (ADNC), Lewy body disease (LBD), vascular brain injury (VBI), and limbic-predominant age-related TDP43 encephalopathy neuropathologic change (LATE-NC). Using linear mixed-effects models, we examined trajectories of cognitive decline for ADNC alone compared to ADNC plus LBD, VBI, or LATE-NC. We also examined differences between observed trajectories and trajectories that would be expected if the neuropathologic entities exerted their effects independently (additively). ADNC+LBD had worse decline than ADNC alone for 4 of the 5 domains with rate of decline consistent with an additive model for all 4 domains. ADNC+LATE-NC had worse decline than ADNC alone for 3 domains with rate of decline additive for only one and }

@article {pmid42024736,
year = {2026},
author = {Zhang, L and Ma, Q and Kong, X and Zou, W and Wang, B and Wu, B and Cai, S and Bai, T and Tan, R and Dai, Z and Liu, X and Jia, Z and Zhang, M and Li, T and Zheng, Y and Hu, X and Wu, J and Xu, Z and Zhou, H},
title = {Mapping transcription factor functions in astrocytes using in vivo gain-of-function Perturb-seq.},
journal = {Science (New York, N.Y.)},
volume = {392},
number = {6796},
pages = {eadw2156},
doi = {10.1126/science.adw2156},
pmid = {42024736},
issn = {1095-9203},
mesh = {Animals ; *Astrocytes/metabolism ; Mice ; *Transcription Factors/genetics/metabolism ; *Alzheimer Disease/genetics/therapy/metabolism ; Disease Models, Animal ; Humans ; Gene Expression Regulation ; Brain/metabolism ; },
abstract = {An in vivo approach combining high-throughput screening with cell type-specific readouts could enable elucidation of genotype-phenotype relationships in complex tissues. We developed an in vivo gain-of-function Perturb-seq platform, termed iGOF-Perturb-seq, to build a functional atlas of ~1000 transcription factors (TFs) in astrocytes, a cell type essential to many brain functions. We then identified cofunctional modules, annotated uncharacterized TFs, and predicted disease-associated TF clusters. Furthermore, iGOF-Perturb-seq performed in a mouse neuroinflammatory model identified Ferd3l as a therapeutic candidate, and astrocyte-specific overexpression of Ferd3l alleviated Alzheimer's disease symptoms in mice. This study provides resources for understanding gene regulation and disease mechanisms in vivo and for identifying potential therapeutic targets for different brain diseases.},
}

Animals
*Astrocytes/metabolism
Mice
*Transcription Factors/genetics/metabolism
*Alzheimer Disease/genetics/therapy/metabolism
Disease Models, Animal
Humans
Gene Expression Regulation
Brain/metabolism

@article {pmid42024796,
year = {2026},
author = {Mei, J and Xia, M and Peng, L and Li, X},
title = {Alcohol and neurodegenerative diseases: a review of mechanistic insights and disease specific effects.},
journal = {The American journal of drug and alcohol abuse},
volume = {},
number = {},
pages = {1-16},
doi = {10.1080/00952990.2026.2645215},
pmid = {42024796},
issn = {1097-9891},
abstract = {Background: Neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD) represent a significant global public health problem. Alcohol consumption is a common lifestyle factor that has been implicated as both a risk factor and potential modifier of disease progression.Objectives: This review integrates evidence from human and experimental studies to characterize the effects of alcohol consumption on the onset and progression of major neurodegenerative diseases.Methods: A narrative review was undertaken examining the pathophysiological effects of alcohol on the brain and its disease-specific effects on neurodegenerative disorders, integrating findings from human cohort studies and mechanistic investigations in preclinical models.Results: Experimental evidence indicates that chronic alcohol consumption exacerbates neurodegeneration through multiple converging mechanisms, including oxidative stress, mitochondrial dysfunction, lipid peroxidation, inflammatory signaling, disruption of neurotrophic pathways, impairment of dopaminergic neurotransmission, and alcohol-induced gut microbiota dysbiosis with blood-brain barrier compromise. Epidemiological data suggest dose-dependent and disease-specific associations, with heavy and sustained consumption more consistently linked to increased risk or accelerated progression of AD and PD, while evidence in ALS and HD remains inconsistent.Conclusion: Alcohol exerts a multifaceted and context-dependent influence on neurodegenerative diseases. Accumulating evidence supports that long-term heavy alcohol consumption is associated with enhanced neurodegeneration. Minimizing alcohol consumption may present a pragmatic opportunity to reduce neurodegenerative risk.},
}

@article {pmid42024924,
year = {2026},
author = {Choo, M and Oh, Y and Hong, LS and Scheitler, KM and Tang-Cabrera, J and Shin, J and Blaha, CD and Shin, H and Park, S and Lee, KH},
title = {Deep Brain Stimulation: Past, Present, and Future.},
journal = {IEEE transactions on bio-medical engineering},
volume = {PP},
number = {},
pages = {},
doi = {10.1109/TBME.2026.3686882},
pmid = {42024924},
issn = {1558-2531},
abstract = {Deep brain stimulation (DBS) has emerged as a revolutionary neurosurgical treatment for various movement and psychiatric disorders. Its development, rooted in advances in stereotactic surgery and early thalamotomies, led to its FDA approval for essential tremor (1997) and Parkinson's disease (2002), followed by applications in dystonia, obsessive-compulsive disorder (OCD), and epilepsy. While DBS has proven effective in these domains, research continues to explore its potential for treating conditions like Alzheimer's disease, addiction, and depression. Despite its clinical success, the underlying mechanisms of DBS remain poorly understood, motivating ongoing studies on neural circuitry modulation. Current DBS applications focus on specific brain targets, such as the subthalamic nucleus for Parkinson's and the anterior nucleus of the thalamus for epilepsy, with new targets under investigation for conditions like OCD and chronic pain. Technological advancements in DBS hardware, including rechargeable implants and directional electrodes, have improved patient outcomes by enhancing precision and reducing side effects. Furthermore, innovations in neuroimaging and closed-loop DBS systems are expanding the capabilities of DBS, offering personalized treatments based on real-time neural feedback. This review highlights the historical evolution, current clinical applications, and future directions of DBS as a transformative therapy for neurological and psychiatric disorders.},
}

@article {pmid42024965,
year = {2026},
author = {Irisarri, A and Bellver-Sanchis, A and Choudhary, BS and Mallo-Abreu, A and Labrador, L and Casadesus, G and Pérez, B and Jana, A and Banerjee, DR and Iriepa, I and Isabel Loza, M and Brea, J and Val, C and Pallàs, M and Muñoz-Torrero, D and Griñán-Ferré, C},
title = {Structure-based virtual screening, in vitro and in silico analysis identified novel potent m6A demethylase FTO inhibitors as promising neurotherapeutic agents.},
journal = {European journal of medicinal chemistry},
volume = {312},
number = {},
pages = {118852},
doi = {10.1016/j.ejmech.2026.118852},
pmid = {42024965},
issn = {1768-3254},
abstract = {Dysregulation of the m6A RNA demethylase FTO has been implicated in neurodegeneration, but brain-penetrant, selective inhibitors remain scarce. Here, we used structure-based virtual screening of a CNS-oriented library to identify novel FTO inhibitors and characterized their permeability, selectivity, and pharmacological profiles. Among them, compound VI showed low-micromolar inhibition of human FTO, selectivity over ALKBH5, high PAMPA-BBB permeability, and oral exposure with measurable plasma levels, moderate brain penetration, and CSF detectability. Molecular dynamics simulations confirmed stable binding of VI within the FTO catalytic pocket, consistent with its enzymatic potency and selectivity. In differentiated SH-SY5Y cells, VI protected against Aβ1-42-induced toxicity while increasing global m6A levels and dampening pro-inflammatory gene expression. In SAMP8 mice, chronic oral treatment with VI (3 mg/kg) ameliorated anxiety-like behavior and rescued hippocampal-dependent spatial and recognition memory, concomitant with increased brain m6A and normalization of synaptic and neuroinflammatory markers. Overall, our findings identify compound VI as a selective, brain-penetrant FTO inhibitor with favorable pharmacokinetics and disease-modifying efficacy in a sporadic Alzheimer's disease model, supporting its further development as a neurotherapeutic candidate.},
}

@article {pmid42025041,
year = {2026},
author = {Akhtar, M and Quadir, A and Tanveer, M and Arshad, M and , },
title = {Dual-center RAPID-LSSVM: Radius-adaptive, probability and imbalance driven weighting for Alzheimer's diagnosis.},
journal = {Neural networks : the official journal of the International Neural Network Society},
volume = {202},
number = {},
pages = {108956},
doi = {10.1016/j.neunet.2026.108956},
pmid = {42025041},
issn = {1879-2782},
abstract = {Alzheimer's disease (AD) is a leading neurodegenerative disorder and the primary cause of dementia, where early, reliable diagnosis remains challenging. Although many machine learning methods have been developed for early AD detection, their performance often degrades under label noise, outliers, and class imbalance. To counter these issues, we propose RAPID, a Radius-Adaptive, Probability and Imbalance Driven flexible weighting mechanism, and integrate it into least-squares SVM to obtain two models: RAPID-LSSVM-I (mean-center) and RAPID-LSSVM-II (median-center). RAPID combines three complementary components. First, a radius-adaptive proximity weight that plateaus for samples near the class center and decays smoothly beyond a threshold, preserving the influence of boundary samples while improving robustness to central noise. Second, a local class-probability term that down-weights potentially mislabeled or ambiguous instances, and third, an imbalance-ratio term that compensates for class prior skew. The dual-center design enables either conventional mean centering or a median-based center that is resilient to outliers and asymmetric distributions. To validate the effectiveness of the proposed RAPID-LSSVM models, experiments are conducted on benchmark KEEL and UCI datasets under both clean and label-noise settings. Additionally, we tested the models on the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset for AD diagnosis. Empirical findings demonstrate the superiority of the RAPID-LSSVM models over baseline models, highlighting their potential in improving AD diagnosis and handling noisy data.},
}

@article {pmid42025146,
year = {2026},
author = {Su, WM and Duan, QQ and He, SY and Liu, RY and Wen, XJ and Zhang, N and Gu, XJ and Yin, KF and Chen, T and Cao, B and Chen, YP},
title = {Hepatic dysfunction and long-term risk of neurodegenerative diseases: A UK Biobank-based analysis.},
journal = {Archives of gerontology and geriatrics},
volume = {147},
number = {},
pages = {106252},
doi = {10.1016/j.archger.2026.106252},
pmid = {42025146},
issn = {1872-6976},
abstract = {OBJECTIVE: Neurodegenerative diseases (NDDs) are incurable disorders with diverse etiologies; emerging evidence links liver health to NDDs' risk, yet no clinical systematic investigation exists.

METHODS: We examined liver health (assessed via 6 blood biochemistry, 21 hepatokines, 2 imaging markers, 8 liver diseases) and its link to NDDs. The NDDs encompassed Alzheimer's disease (AD), frontotemporal dementia (FTD), unspecified dementia, vascular dementia (VaD), all-cause dementia (ACD), Parkinson's disease (PD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP), all-cause parkinsonism, dystonia (DYT), and motor neuron disease (MND). Cox regression analysis was employed across four models, and distinct discriminative models were further constructed for each NDDs.

RESULTS: Analysis of 502,163 participants in the UK Biobank revealed disease-specific associations between the liver health and NDDs. The highest number of significant liver-related factors, across at least three analysis models, was observed for VaD with 13 factors, followed by ACD with 10 factors, unspecified dementia with 9 factors, and AD with 7 factors. For non-dementia related NDDs, fewer associations were detected: 3 factors for PD, 3 for all-cause parkinsonism, 2 for DYT, and single factors for MSA, PSP, and MND. Ten significant-liver-factor-based models (beyond FTD) demonstrated a strong discriminative ability for NDDs incidence, especially dementia-related outcomes. The 5-year and 10-year AUC values were as follows: 0.781/0.834 for AD; 0.907/0.888 for VaD; 0.799/0.857 for unspecified dementia; 0.808/0.834 for ACD.

CONCLUSION: These findings firmly establish liver health as a potential target for the evaluation of NDDs' risk and our results suggest that interventions designed to safeguard liver might represent a preventive strategy against neurodegeneration.},
}

@article {pmid42025299,
year = {2026},
author = {Fu, JF and Juttukonda, MR and Garimella, AH and Mercaldo, ND and Wey, HY and Salvatore, A and Dickerson, BC and Price, JC},
title = {Impact of Postlabeling Delay on Arterial Spin-Labeling MRI-Based Measures of Cerebral Blood Flow in a Simultaneous PET/MRI Study of Aging.},
journal = {AJNR. American journal of neuroradiology},
volume = {},
number = {},
pages = {},
doi = {10.3174/ajnr.A9130},
pmid = {42025299},
issn = {1936-959X},
abstract = {BACKGROUND AND PURPOSE: Arterial spin-labeling (ASL) MRI with a single postlabeling delay (PLD) of 1800 msec is recommended for quantifying CBF when the PLD is sufficiently longer than the arterial transit time. However, this condition may not be satisfied in older participants or individuals with dementia, for whom multiple PLDs may be more beneficial. This work assessed the intermediate-term (4-week) test-retest reliability and accuracy of single- versus multiple-PLD ASL for quantifying CBF relative to [[15]O]water PET acquired using PET/MRI imaging in a study of aging and Alzheimer disease (AD).

MATERIALS AND METHODS: Cognitively normal young (n=3) and older participants (n=5) and patients with AD (n=3) underwent PET/MRI sessions. ASL CBF was quantified separately using PLDs of 1800, 2000, 2200, and 2400 msec, and using multiple-PLD approach combining all 4 PLDs. A subset of participants (1 AD, 4 older cognitively normal) underwent repeated ASL MRI after approximately 4 weeks for test-retest evaluation, assessed using Bland-Altman plots and intraclass correlation coefficients (ICCs). Accuracy was assessed by comparing ASL CBF with [[15]O]water PET using Spearman correlation across cortical regions and vascular territories.

RESULTS: The 4-week test-retest reliability was highest for single-PLD ASL using 1800 msec (ICC > 0.75) and lowest for single-PLD of 2400 msec (ICC: 0.1-0.8). Multiple-PLD ASL showed better reliability than the 2400 msec PLD but was not superior to shorter PLDs. Correlations with [[15]O]water PET were strongest for 1800 msec single-PLD and generally decreased with longer PLDs, except the occipital lobe, where all PLDs showed poor agreement. Multiple-PLD ASL showed similar correlation strengths as 2000 msec single-PLD.

CONCLUSIONS: Single-PLD ASL with 1800 msec PLD demonstrated the best balance of reliability and agreement with [[15]O]water PET, suggesting it may be an effective choice for studying CBF in aging and AD populations. While multiple-PLD ASL offered comparable performance, it did not confer notable benefits compared with the best-performing single-PLD under similar acquisition time constraints. These findings underscore the importance of PLD selection in ASL protocols in older or cognitively impaired cohorts and highlight the value of assessing intermediate-term reliability in longitudinal studies.},
}

@article {pmid42025412,
year = {2026},
author = {Vellas, B},
title = {Healthy longevity, intrinsic capacity, geroscience and Alzheimer's disease prevention.},
journal = {The journal of prevention of Alzheimer's disease},
volume = {13},
number = {5},
pages = {100570},
doi = {10.1016/j.tjpad.2026.100570},
pmid = {42025412},
issn = {2426-0266},
}

@article {pmid42025633,
year = {2026},
author = {Yuan, Q and He, S and Elhassan, MAM and Yu, C and Lu, J and Fang, L and Zhu, X and Wu, Z and He, J and Gu, W},
title = {Peripheral inflammation mediates the association between triglyceride-glucose index and cognitive impairment in comorbid major depressive disorder and type 2 diabetes: Translational implications for Alzheimer's disease risk via neuroinflammatory pathways.},
journal = {Journal of affective disorders},
volume = {},
number = {},
pages = {121830},
doi = {10.1016/j.jad.2026.121830},
pmid = {42025633},
issn = {1573-2517},
abstract = {BACKGROUND: Comorbid major depressive disorder (MDD) and type 2 diabetes mellitus (T2DM) are associated with accelerated cognitive impairment, potentially involving shared immunometabolic and inflammatory mechanisms. The triglyceride-glucose (TyG) index, a surrogate of insulin resistance, has been linked to inflammation. This study examined whether peripheral inflammation statistically mediates the association between TyG and cognitive impairment in patients with comorbid MDD and T2DM.

METHODS: In this cross-sectional study, 256 patients with MDD and T2DM were enrolled. Cognitive impairment was defined as MoCA <26. Peripheral inflammatory markers (CRP, IL-6, TNF-α) and plasma Alzheimer's disease-related biomarkers (Aβ42/40 ratio, p-tau217) were measured. Multivariable logistic regression and mediation analyses were conducted with adjustment for relevant covariates.

RESULTS: Cognitive impairment was present in 59.37% of participants. Patients with impairment had higher TyG and inflammatory markers (all P < 0.001). TyG was independently associated with cognitive impairment (OR = 2.87, 95% CI: 1.68-4.91). TyG correlated with CRP, IL-6, and TNF-α (r = 0.35-0.42). Peripheral inflammation statistically mediated 28.41% of the TyG-cognition association. Impaired patients showed lower Aβ42/40 and higher p-tau217 (P < 0.001). Serial mediation suggested an indirect association via inflammation and p-tau217 (β = 0.10, 95% CI: 0.03-0.22), accounting for 12% of the total association.

CONCLUSIONS: Higher TyG index was statistically associated with cognitive impairment in comorbid MDD and T2DM, partly mediated by peripheral inflammation. While these cross-sectional findings highlight the potential of TyG as an accessible biomarker, longitudinal studies are needed to establish causality and directionality.},
}

@article {pmid42025717,
year = {2026},
author = {Sis, CO and Yıldız, O and Elci, MP and Fatsa, T and Oren, S},
title = {Neuroprotective and therapeutic effects of magnesium L-threonate in an amyloid β1-42 induced SH-SY5Y cell model of Alzheimer's disease.},
journal = {Brain research},
volume = {},
number = {},
pages = {150341},
doi = {10.1016/j.brainres.2026.150341},
pmid = {42025717},
issn = {1872-6240},
}

@article {pmid42025718,
year = {2026},
author = {Li, Y and Chen, J},
title = {Lentinan attenuates tau phosphorylation and memory deficits in hTau-overexpressing mice.},
journal = {Brain research},
volume = {},
number = {},
pages = {150340},
doi = {10.1016/j.brainres.2026.150340},
pmid = {42025718},
issn = {1872-6240},
abstract = {BACKGROUND: Lentinan (LNT), a polysaccharide extracted from shiitake mushrooms, has been long used in Asia for improving health. Although LNT injections have been approved for cancer treatment in multiple Asian countries, the potential of LNT in alleviating Alzheimer's disease (AD) pathology and associated cognitive impairments remains poorly understood. Thus, this study aimed to assess the neuroprotective effects of LNT.

METHODS: In vitro tests were performed in HEK 293/tau cells. Moreover, to simulate AD tau pathology, human full-length tau (hTau) expression was induced using adeno-associated virus serotype 2 (AAV2) in C57/BL6 mice. Intragastric LNT administration for 1 month markedly elevated protein phosphatase 2A (PP2A) activity and decreased tau phosphorylation at Ser202/Thr205 (AT8) in AAV2-hTau infected mice.

RESULTS: LNT significantly enhanced cell viability and PP2A activity while reducing tau phosphorylation in HEK 293/tau cells. Furthermore, behavioral tests demonstrated that LNT mitigated cognitive defects induced through hTau overexpression while significantly increasing the expression of synaptic protein expression such as synaptotagmin and synaptophysin.

CONCLUSIONS: Our findings suggest that LNT can prevent AD-like tau hyperphosphorylation by activating PP2A and attenuate AD-like cognitive impairments by restoring synaptic plasticity and synaptogenesis. Therefore, LNT is a potential therapeutic candidate for treating tau-related diseases.},
}

@article {pmid42025774,
year = {2026},
author = {Xing, L and Liu, A and Gao, W and Li, J and Yao, M and Song, J and Duan, P and Li, H},
title = {Organelle Interactome Disruption: The Systemic Pathological Mechanisms and Therapeutic Prospects of Mitochondria-Lysosome-ER Crosstalk in Alzheimer's Disease.},
journal = {Ageing research reviews},
volume = {},
number = {},
pages = {103145},
doi = {10.1016/j.arr.2026.103145},
pmid = {42025774},
issn = {1872-9649},
abstract = {The traditional pathological framework of Alzheimer's disease (AD) primarily focuses on the accumulation of β-amyloid (Aβ) and tau proteins. However, therapeutic strategies targeting these molecules have repeatedly encountered setbacks in clinical translation. Recent studies have progressively revealed that the dynamic interaction network among intracellular organelles plays a central role in the pathogenesis of AD. This systematic review examines the independent dysfunctions of three key organelles-mitochondria, lysosomes, and the endoplasmic reticulum (ER)-in AD, along with their physical and functional connectivity mechanisms. It emphasizes how their interaction network, formed through membrane contact sites, synergistically drives core AD pathological processes, including calcium signaling dysregulation, Aβ metabolism imbalance, mitochondrial quality control failure, lipid metabolism disorders, and neuroinflammation with apoptosis. This paper innovatively proposes that AD can be regarded as a "mitochondrial network disorder," the pathological essence of which lies in the systemic breakdown of communication between mitochondria. Building on this premise, we further discuss a therapeutic strategy centered on mitophagy enhancers to reshape the mitochondrial network and explore the translational medical prospects of achieving multi-target synergistic intervention by restoring the homeostasis of the mitochondrial network.},
}

@article {pmid42025804,
year = {2026},
author = {Woodard, GE},
title = {C3 and C5 Complement Cascade Activation in Brain Injury and Disease: Molecular Mechanisms, Pathological Roles, and Therapeutic Implications.},
journal = {Neurochemistry international},
volume = {},
number = {},
pages = {106161},
doi = {10.1016/j.neuint.2026.106161},
pmid = {42025804},
issn = {1872-9754},
abstract = {The complement system represents a crucial component of innate immunity with increasingly recognized roles in central nervous system pathology and homeostasis. Complement components C3 and C5 serve as central molecular hubs in the complement cascade, orchestrating inflammatory responses, synaptic pruning, and neuronal injury across diverse neurological conditions. This comprehensive review examines the molecular mechanisms underlying C3 and C5 activation in the brain, their pathological contributions to acute brain injuries including traumatic brain injury and ischemic stroke, and their complex involvement in chronic neurodegenerative diseases such as Alzheimer disease, multiple sclerosis, Parkinson disease, Huntington disease, and amyotrophic lateral sclerosis. Emerging evidence demonstrates that complement activation in the central nervous system extends beyond traditional immune functions to encompass critical roles in neurodevelopment, synaptic plasticity, and neural circuit refinement. The dual nature of complement function in the brain, exhibiting both neuroprotective and neurodegenerative properties depending on context and activation levels, presents unique therapeutic challenges and opportunities. This review synthesizes current understanding of complement-mediated neuroinflammation, discusses validated and emerging therapeutic strategies targeting C3 and C5, evaluates complement biomarkers for disease diagnosis and monitoring, and identifies critical knowledge gaps requiring future investigation. Understanding the nuanced roles of C3 and C5 in neurological disease provides essential foundations for developing targeted immunomodulatory therapies that preserve beneficial complement functions while mitigating pathological activation.},
}

@article {pmid42025825,
year = {2026},
author = {Liu, S and Yang, C and Zhang, N and Xiang, L and Li, F and Qi, L and Xu, X},
title = {AXL prevents amyloid-β-induced microglial ferroptosis by sustaining SLC2A3-mediated mitochondrial respiration.},
journal = {Pharmacological research},
volume = {},
number = {},
pages = {108203},
doi = {10.1016/j.phrs.2026.108203},
pmid = {42025825},
issn = {1096-1186},
abstract = {Dysregulated iron metabolism is a pivotal driver of Alzheimer's disease (AD). Excess iron promotes Aβ aggregation and tau hyperphosphorylation, thereby accelerating disease progression. Serving as the primary iron reservoir in the central nervous system, microglia are intrinsically susceptible to ferroptosis, thereby amplifying neurotoxicity to neighboring neurons. While plaque-associated receptors (e.g., TREM2, AXL, MERTK) govern microglial responses, their precise contribution to metabolic susceptibility to ferroptosis remains elusive. Here, we identify the receptor tyrosine kinase AXL as a critical metabolic safeguard against Aβ-induced ferroptosis in microglia. Mechanistically, our findings indicate that, under our experimental conditions, oAβ exposure is associated with downregulation of AXL in microglia, thereby impairing SLC2A3-dependent glucose uptake and mitochondrial ATP production, which ultimately increases ferroptotic vulnerability. Moreover, through an optimized surface plasmon resonance imaging (SPRi) screening approach, we identified the FDA-approved drug levothyroxine (L-T4) as a potent AXL agonist. L-T4 treatment restores microglial homeostasis, inhibits Aβ-induced ferroptosis, and ameliorates neuropathology in vivo. These findings establish AXL as a novel metabolic safeguard in microglia and highlight L-T4 as a promising therapeutic strategy for AD and other ferroptosis-related disorders via drug repurposing.},
}

@article {pmid42025827,
year = {2026},
author = {Lin, Z and Zhang, S and Sun, M},
title = {Targeting Mitochondrial Quality Control in Alzheimer's Disease: Mechanisms and Therapeutic Potential of Phytomedicines.},
journal = {Pharmacological research},
volume = {},
number = {},
pages = {108202},
doi = {10.1016/j.phrs.2026.108202},
pmid = {42025827},
issn = {1096-1186},
abstract = {Alzheimer's disease (AD) is a neurodegenerative disorder driven partly by mitochondrial dysfunction, notably the failure of mitochondrial quality control (MQC). Phytochemicals have emerged as multi-target agents capable of restoring MQC, offering a promising therapeutic avenue. This review outlines how dysregulated MQC contributes to AD pathogenesis and summarizes the current evidence on phytochemicals that target key MQC processes-including mitochondrial dynamics, biogenesis, mitophagy, oxidative stress, and apoptosis-to exert neuroprotection. In AD, MQC is broadly impaired, characterized by suppressed biogenesis, excessive mitochondrial fission, defective mitophagy, oxidative stress, and calcium dyshomeostasis. Phytochemicals counter these defects through diverse mechanisms: restoring fission-fusion balance, enhancing biogenesis and mitophagic clearance, attenuating oxidative stress via Nrf2 activation, and inhibiting mitochondria-dependent apoptosis by modulating Bcl-2 family proteins and caspases. Despite these promising preclinical findings, several challenges remain, including poor bioavailability, limited blood-brain barrier penetration, lack of standardized preparations, and insufficient clinical validation. This review provides a mechanistic rationale for targeting MQC in AD and highlights future directions for translating phytochemical-based strategies into effective therapies.},
}

@article {pmid42025961,
year = {2026},
author = {Hajibandeh, S and Tao, YA and Hsieh, MH and Liu, HG and Cheng, YF and Lee, KH and Hsieh, SY and Lu, CH},
title = {Semaglutide for obesity management: A narrative review of efficacy, safety, and future directions.},
journal = {Journal of the American Pharmacists Association : JAPhA},
volume = {},
number = {},
pages = {103117},
doi = {10.1016/j.japh.2026.103117},
pmid = {42025961},
issn = {1544-3450},
abstract = {BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), particularly semaglutide, have demonstrated substantial efficacy for glycemic control and weight management and are increasingly prescribed across diverse populations. Rapid expansion of indications, formulations, and real-world use has outpaced comprehensive evaluation of long-term safety, tolerability, and adherence, raising important concerns for clinical practice.

OBJECTIVES: This narrative review aims to synthesize current evidence on the efficacy and safety profile of semaglutide, with a focus on adverse events, treatment persistence, perioperative considerations, and use in special populations, to support clinical decision-making and pharmacist-led patient care.

METHODS: A review of clinical trials, observational studies, pharmacovigilance reports, regulatory communications, and professional guidelines was conducted. Evidence was drawn from randomized controlled trials, post-marketing safety reports, systematic reviews, and relevant clinical and regulatory documents.

RESULTS: From 1525 records, 34 studies and reports were included. Clinical trials consistently demonstrated meaningful weight reduction with semaglutide. Evidence regarding acute pancreatitis remains limited, although cases have been reported in clinical trials and postmarketing safety analyses. Evidence regarding suicidal ideation associated with semaglutide is mixed, with some analyses suggesting potential safety signals while others report no increased risk. Recent multi society clinical guidelines have addressed perioperative management of GLP-1 RAs, generally supporting individualized perioperative assessment. Emerging literature also examines semaglutide use in special populations, including patients with Alzheimer disease and individuals following bariatric surgery, although long-term neurologic and post-bariatric safety outcomes remain incompletely characterized.

CONCLUSIONS: Semaglutide represents an important therapeutic option for chronic weight management. As clinical use expands, continued evaluation of long-term safety, tolerability, and treatment persistence will be important. Pharmacists play a key role in counseling patients, monitoring adverse effects, supporting adherence, and contributing to multidisciplinary obesity care.},
}

@article {pmid42026042,
year = {2026},
author = {Su, D and Li, H and Pan, L and Huang, H and Xiao, T and Chen, G and Tan, W and Bu, L and Zhang, Z},
title = {TNMD BRICHOS domain attenuates tau pathology and memory deficits in a mouse model of tauopathy.},
journal = {Cell death & disease},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41419-026-08749-3},
pmid = {42026042},
issn = {2041-4889},
abstract = {The aberrant aggregation of tau leads to loss of its physiological functions and gain of toxic functions, and plays a crucial role in the pathogenesis of tauopathies including Alzheimer's disease (AD). Targeting tau aggregation is considered a promising strategy for treating tauopathies. The BRICHOS family consists of a variety of proteins containing the BRICHOS domain. Certain endogenous BRICHOS domains may inhibit the pathological aggregation of disease-associated proteins. However, the effects of the BRICHOS domains on tau aggregation remain unknown. Here we revealed that BRICHOS domains from integral membrane protein 2B (ITM2B), tenomodulin (TNMD), and out at first (OAF) bind to tau and inhibit its aggregation in vitro. Intravenous administration of TNMD BRICHOS alleviates tau aggregation, synaptic dysfunction, and memory deficits in Tau P301S transgenic mice. Thus, TNMD BRICHOS may serve as a potential therapeutic approach for the development of treatments for tauopathies.},
}

@article {pmid42026067,
year = {2026},
author = {Michel, JJ and Sanghvi, K and Rosenbauer, J and Humbs, L and Dierssen, CT and Grudzenski-Theis, S and Sachs, V and Jähne, K and Degenhardt, K and Frölich, L and Herms, J and Fatar, M and Platten, M and Bunse, L},
title = {Type I interferon drives T cell responses to amyloid beta in the central nervous system.},
journal = {Nature communications},
volume = {17},
number = {1},
pages = {},
pmid = {42026067},
issn = {2041-1723},
mesh = {Animals ; *Amyloid beta-Peptides/metabolism/immunology ; Mice, Transgenic ; Mice ; *Interferon Type I/metabolism/immunology ; Humans ; *CD8-Positive T-Lymphocytes/immunology/metabolism ; Chemokine CXCL10/metabolism/immunology ; *Alzheimer Disease/immunology/pathology/metabolism ; *Central Nervous System/immunology/metabolism/pathology ; Plaque, Amyloid/immunology/pathology/metabolism ; Receptors, CXCR3/metabolism ; Disease Models, Animal ; Microglia/immunology/metabolism ; Cerebral Amyloid Angiopathy/immunology/pathology ; Signal Transduction ; Mice, Inbred C57BL ; Male ; Female ; Brain/pathology/immunology ; },
abstract = {Amyloid beta (Aβ) plaque deposition in the central nervous system (CNS) is a hallmark of Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA), triggering robust innate immune responses. However, the role of the adaptive immune system remains less well understood. Here we show the immune microenvironment dynamics in APP23 transgenic (APP23-tg) mice modelling CNS amyloid pathology, using single-cell transcriptomics. We observed a marked increase in T-cell populations during late disease stages, particularly CD8[+] T-cells that clustered around Aβ plaques, suggesting a targeted immune response. Among these, we identified an Aβ plaque-associated subset of CD8[+] T cells expressing interferon-stimulated genes (ISGs), which promoted Type-I interferon signaling. This subset also produced CXCL10, facilitating the recruitment of non-ISG T cells through the CXCL10-CXCR3 axis. Importantly, similar Type-I interferon responses were detected near plaques in human CNS amyloid pathology. Together, these findings highlight a shift from microglia-driven to T-cell-mediated neuroinflammation as amyloid pathology progresses, with implications for time-resolved therapy development.},
}

Animals
*Amyloid beta-Peptides/metabolism/immunology
Mice, Transgenic
Mice
*Interferon Type I/metabolism/immunology
Humans
*CD8-Positive T-Lymphocytes/immunology/metabolism
Chemokine CXCL10/metabolism/immunology
*Alzheimer Disease/immunology/pathology/metabolism
*Central Nervous System/immunology/metabolism/pathology
Plaque, Amyloid/immunology/pathology/metabolism
Receptors, CXCR3/metabolism
Disease Models, Animal
Microglia/immunology/metabolism
Cerebral Amyloid Angiopathy/immunology/pathology
Signal Transduction
Mice, Inbred C57BL
Male
Female
Brain/pathology/immunology

@article {pmid42026117,
year = {2026},
author = {Peng, B and Du, L and Dang, M and Li, T and Li, Z and Liu, J and Chen, Y and Liu, B and Zhang, Z},
title = {Decoupling MCI-specific signatures from shared neurobiological substrates of cognitive aging via deep learning.},
journal = {NPJ digital medicine},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41746-026-02597-3},
pmid = {42026117},
issn = {2398-6352},
support = {Grant No. 82425024//the National Natural Science Foundation of China/ ; Grant No. 2022ZD0211600//the Science and Technology Innovation 2030 Major Projects/ ; Grant No. 2023YFC3605400//the National Key Research and Development Program of China/ ; GZC20252268//Postdoctoral Fellowship Program (Grade C) of China Postscience Foundation/ ; No. CX202408//Innovation Team for Clinical & Basic Research, Shandong First Medical University/ ; },
abstract = {The specific neuroanatomy of mild cognitive impairment (MCI) is obscured by its clinical heterogeneity and confounding effects from normative variation. This problem is compounded by the inability of conventional neuroimaging methods to disentangle these overlapping influences. Leveraging data from the Beijing Aging Brain Rejuvenation Initiative (BABRI, n = 918) and the Alzheimer's Disease Neuroimaging Initiative (ADNI, n = 1293), this study employed a conditional variational autoencoder (CVAE) to: (1) systematically distinguish between aging-related cognitive decline and MCI-specific cognitive impairments; (2) implicitly disentangle latent, unknown confounding effects to identify MCI-specific structural brain alterations; and (3) construct individualized scores for predicting the risk of conversion to Alzheimer's disease (AD). The CVAE effectively extracted MCI-specific latent features from T1 structural MRI, significantly correlated with episodic memory, attention, and executive function impairments. Reconstructions revealed characteristic deformation in regions including the middle and medial temporal lobes, frontal lobe, limbic system, and cerebellum. The robustness of this structural-cognitive impairment association model established in BABRI dataset was validated in the ADNI dataset. Moreover, predictive modeling using these features achieved superior AD-conversion prediction (AUC = 0.83) versus whole-brain atrophy (AUC = 0.74; p < 0.001) or CSF biomarkers (AUC = 0.77; p < 0.001).This work establishes a novel paradigm for isolating MCI-specific brain alterations from physiological aging.},
}

@article {pmid42026226,
year = {2026},
author = {Yu, Z and Lin, Y and Yang, E and Ji, X and Liu, J and Jiao, Y},
title = {Context-Dependent Regulation of Microglial Metabolic and Immune States via IL-3/CD123 Signaling: Implications for Glial Crosstalk and Cognitive Impairment.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {},
pmid = {42026226},
issn = {1559-1182},
support = {SCU2024D005//Fundamental Research Funds for the Central Universities/ ; 2024-BS-167//Natural Science Foundation of Liaoning Province/ ; 82301549//National Natural Science Foundation of China/ ; },
mesh = {Humans ; *Microglia/metabolism/immunology ; Animals ; *Cognitive Dysfunction/metabolism/immunology/pathology ; *Signal Transduction ; *Interleukin-3/metabolism ; *Neuroglia/metabolism ; *Cell Communication ; },
abstract = {Cognitive impairment (CI), spanning mild memory issues to severe dementia, impacts over 55 million people worldwide and have a significant effect that strains health, economy, and caregiving. Surprisingly, it occurs at any age. The glial cell ecosystem, particularly astrocyte-microglia crosstalk, is pivotal for brain homeostasis and cognitive function across the lifespan. Intriguingly, in recent discoveries, dysregulation of ecosystem contributes to neurodevelopmental disorders (NDDs), adult cognitive decline, and neurodegenerative diseases like Alzheimer's disease (AD), and astrocyte-derived interleukin-3 (IL-3), acting via the IL-3/CD123-related signals, may act as a key regulatory mediator of microglial function. Over the past few decades, extensive researches have been devoted to investigating aging-related regulatory factors with the aim of deciphering the "code" underlying cognitive developmental abnormalities, premature cognitive decline, and neurodegeneration. Astrocyte-microglia crosstalk governs age-dependent glial turnover via senescence-sensitive IL-3. Under pathological conditions, perturbed turnover's association with age-stratified CI and its regulators is poorly understood. This review integrates current evidence on glial crosstalk, cellular senescence, and repopulation to elucidate age-specific CI driven by dysregulated glial turnover, while identifying key biomarkers that can predict aging processes. Looking ahead, therapeutic strategies targeting the IL-3/CD123-related signals regulating glial crosstalk hold promise for advancing interventions in immune-mediated CI across the lifespan.},
}

Humans
*Microglia/metabolism/immunology
Animals
*Cognitive Dysfunction/metabolism/immunology/pathology
*Signal Transduction
*Interleukin-3/metabolism
*Neuroglia/metabolism
*Cell Communication

@article {pmid42026238,
year = {2026},
author = {Manni, E and Al-Kuraishy, HM and Eisawy, R and Abdelaziz, AM and Batiha, GE},
title = {Reimagining GSK-3β Therapeutics in Alzheimer's Disease: From Inhibition to Activity Normalization and Targeted Degradation.},
journal = {Journal of molecular neuroscience : MN},
volume = {76},
number = {2},
pages = {},
pmid = {42026238},
issn = {1559-1166},
}

@article {pmid42014405,
year = {2026},
author = {Da Silva, IIN and Ramirez, D and Parylak, SL and Wallace, LA and Tucker, JK and Erberich, JM and Katariya, R and McDonald, AH and Gallina, IS and Tucker, AL and Burgado, J and Jaeger, BN and Barron, JJ and Pratt, JM and Pena, M and Racha, V and Lim, CK and Fernandes, S and Benassi, S and Randolph-Moore, L and Vadodaria, KC and Marchetto, MC and Allen, NJ and Gage, FH},
title = {CK2 inhibition suppresses glial inflammation in models of neuroinflammation and neurodegeneration.},
journal = {Nature communications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41467-026-71736-x},
pmid = {42014405},
issn = {2041-1723},
abstract = {Neuroinflammation plays a key role in Alzheimer's disease (AD) and many other neurodegenerative disorders. Chronic activation of astrocytes and microglia fuels neuronal damage via cytokine secretion, oxidative stress, and proteolysis, yet glial inflammatory regulation remains poorly understood. Using chemoproteomics, we identified CK2, particularly the brain-enriched catalytic subunit CK2α2, as a key driver of astrocytic inflammation. CK2 enhances NF-κB activity by phosphorylating NF-κB S529 and IκBα S32, promoting pro-inflammatory gene expression. Genetic or chemical CK2 inhibition dampens inflammation, including IL-6 and IL-8 expression in a TNFα acute neuroinflammation mouse model. CK2α2 is upregulated in AD postmortem tissues and patient-derived astrocytes. AD astrocytes exhibit a hyperinflammatory state that can be attenuated by CK2 inhibition. Overexpression of CK2α2 in cortical organoids mimics AD pathology, whereas CK2 inhibition using the potent, selective, and brain-penetrant probe TAL606 rescues inflammatory markers in AD APP/PS1 mice. These findings position CK2 as a central regulator of neuroinflammation and a promising therapeutic target for AD and related disorders.},
}

@article {pmid42014422,
year = {2026},
author = {Choi, KE and Pae, AN and Cho, NC},
title = {Mechanistic insights into the disaggregation of amyloid-β fibrils by EPPS via replica-exchange molecular dynamics simulations.},
journal = {Scientific reports},
volume = {16},
number = {1},
pages = {},
pmid = {42014422},
issn = {2045-2322},
}

@article {pmid42014587,
year = {2026},
author = {Williams, J},
title = {Are we fully exploiting genetic discoveries to understand and treat Alzheimer's disease?.},
journal = {Mammalian genome : official journal of the International Mammalian Genome Society},
volume = {37},
number = {1},
pages = {},
pmid = {42014587},
issn = {1432-1777},
}

@article {pmid42014693,
year = {2026},
author = {Liu, P and Xu, Y and Che, P and Wang, Y and Zhang, Y and Ji, D and Wang, C and Ma, X and Sun, M and Zhang, N},
title = {Establishment and validation of an Alzheimer's disease diagnostic model on the basis of exhaled volatile organic compound characteristics.},
journal = {Translational psychiatry},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41398-026-04048-9},
pmid = {42014693},
issn = {2158-3188},
abstract = {Exhaled volatile organic compounds (VOCs) have been investigated in some diseases, including cognitive impairment, in pilot studies. The present study aimed to explore the role of exhaled VOCs in identifying and differentiating patients with Alzheimer's disease (AD). The identification cohort included 241 participants: 99 AD patients (dementia=74, mild cognitive impairment (MCI) = 25), 59 non-AD dementia patients, and 83 cognitively unimpaired controls (CUCs). Proton transfer reaction time-of-flight mass spectrometry (PTR-TOFMS) was employed to detect exhaled VOCs. The differences in VOCs between the AD and CUC groups and between the AD dementia and non-AD dementia groups were compared separately. Furthermore, machine learning models for discriminating AD from CUC as well as AD dementia from non-AD dementia were established. The AD diagnostic model was further validated in an independent cohort of 44 AD patients (dementia=33, MCI = 11) and 35 CUCs. Moreover, we explored the possible metabolic pathways of AD-specific exhaled VOCs with the Human Metabolome Database (HMDB). We detected 60 different VOCs between the AD and CUC groups, among which the top ten were C4H10S, C2H6N2O2, C3H6O3, C4H7F2NO, C6H5NO2, C8H6N2, C3HN, C9H21N, C15H24, and C8H12 (P < 0.001). The AD diagnostic model had an accuracy of 0.93 in the identification cohort according to internal validation and 0.75 in the validation cohort for external validation. The model for discriminating AD dementia patients from non-AD dementia patients had an accuracy of 0.90. Fourteen of the 60 AD-specific VOCs were retrieved from the HMDB, from which the three most significant metabolic pathways were identified, namely, butyrate metabolism, pyruvate metabolism, and glycolysis/gluconeogenesis. These results indicate that exhaled VOC measurement may be a promising approach for diagnosing and differentiating AD, but further validation is needed.},
}

@article {pmid42014714,
year = {2026},
author = {Finney, CA and Shvetcov, A},
title = {Mild cognitive impairment cases affect the predictive power of Alzheimer's disease diagnostic models using routine clinical variables.},
journal = {npj aging},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41514-026-00390-w},
pmid = {42014714},
issn = {2731-6068},
abstract = {Diagnostic models using primary care routine clinical variables have been limited in their ability to identify Alzheimer's disease (AD) patients. In this study, we sought to better understand the effect of mild cognitive impairment (MCI) on the predictive performance of AD diagnostic models. We sourced data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. CatBoost was used to assess the utility of routine clinical variables that are accessible to primary care physicians, such as hematological and blood tests and medical history, in multiclass classification between healthy controls, MCI, and AD. Our results indicated that MCI indeed affected the predictive performance of AD diagnostic models. Of the three subgroups of MCI that we found, this finding was driven by a subgroup of MCI patients who likely have prodromal AD. This work highlights the importance of continuing to focus on better classification of the different types of MCI to improve diagnostic models of AD, rather than focusing on binary classifications between AD and control cases. Future research should focus on distinguishing MCI from prodromal AD as the utmost priority for improving translational AD diagnostic models for primary care physicians.},
}

@article {pmid42014786,
year = {2026},
author = {Kim, OH and Shin, CH and Cho, MW and Ha, JY and Choung, JJ and Song, DK and Choi, JY and Chang, ES and Lee, HJ and Ku, SK},
title = {Transcranial vibrotactile stimulation enhances hippocampal cholinergic signaling and memory through frequency-dependent mechanotransduction.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-49377-3},
pmid = {42014786},
issn = {2045-2322},
abstract = {Cholinergic dysfunction is a key contributor to cognitive impairment observed in aging and neurodegenerative disorders such as Alzheimer's disease (AD). Although acetylcholinesterase (AChE) inhibitors have been the mainstay of symptomatic treatment for over two decades, their limited efficacy and adverse effects underscore the need for alternative therapeutic approaches. Recent evidence indicates that mechanical stimulation can modulate neuronal and glial signaling through mechanotransduction, suggesting a potential strategy to enhance cognitive function via non-pharmacological means. Here, we developed a head-mounted vibrotactile stimulation system (HVSS) that delivers controlled vibration to the cranium and evaluated its effects in a pharmacological model of acute cholinergic dysfunction induced by scopolamine. To this end, male C57BL/6 mice received scopolamine (1 mg/kg, i.p.; on days 7, 14, and 28) and were exposed to daily vibrotactile stimulation at 20, 40, or 80 Hz for 28 days. Behavioral performance was assessed using passive avoidance and Morris water maze tests, followed by biochemical and histological analyses. HVSS at 40 Hz and 80 Hz significantly improved cognitive performance, enhanced hippocampal cholinergic function, reduced oxidative damage, and upregulated memory-related signaling genes, including BDNF, PI3K, AKt, ERK1/2, CREB, and CAMK4. These findings suggest that high-frequency HVSS improves memory hippocampal cholinergic function via activation of memory-related signaling pathways, highlighting its potential as a safe, non-pharmacological neuromodulatory strategy for cholinergic dysfunction-related cognitive decline.},
}

@article {pmid42014834,
year = {2026},
author = {Wang, X and Liu, L and Yang, F and Huang, C and Mei, Z and Li, J and Ma, S},
title = {Identifying omic biomarkers for chronic inflammatory diseases associated with periodontitis using percolation on multi-disease gene co-expression networks.},
journal = {Communications medicine},
volume = {},
number = {},
pages = {},
doi = {10.1038/s43856-026-01591-w},
pmid = {42014834},
issn = {2730-664X},
abstract = {BACKGROUND: Chronic inflammatory diseases, such as ulcerative colitis (UC), Crohn's disease (CD), Alzheimer's disease (AD) and Parkinson's disease (PD) are clinically related to periodontitis. However, the computation of omic biomarkers regarding these diseases has not leveraged this association.

METHODS: We developed PMGCN, a computational framework that employs optimal percolations on multi-disease gene co-expression networks derived from bulk transcriptomic gene expression profiles to identify a parsimonious set of key nodes as candidate omic biomarkers.

RESULTS: Evaluation of PMGCN on independent clinical studies of four chronic inflammatory diseases demonstrates improved predictive performance evaluated via cross validation with bootstrapping compared to commonly used univariate differentially expressed genes. Specifically for UC, three key gene biomarkers (CXCL5, FOSB, PTGR1) are identified by PMGCN, and public single-cell RNA-seq datasets confirm that the mainly altered inflammation signaling pathways in three cell clusters are connected to UC and periodontitis progression.

CONCLUSIONS: PMGCN proposes a computational biomarker identification approach leveraging multi-disease association, the discovered gene biomarkers demonstrate improved prediction of chronic inflammatory diseases and provide novel insights into disease progression.},
}

@article {pmid42014975,
year = {2026},
author = {McGlinchey, E and Pape, S and Zaman, SH and Eustace-Cook, J and Stockbauer, A and Baldimtsi, E and Langballe, EM and Larsen, FK and Sandkühler, K and Ivain, P and Rebillat, AS and Ecrement, P and McCarron, M and Benejam, B and Khoo, WM and Fortea, J and Levin, J and Öhman, F and Granholm-Bentley, AC and Strydom, A and Nübling, G},
title = {Lifestyle intervention and cognitive outcomes in Down syndrome: a horizon 21 European Down syndrome consortium scoping review.},
journal = {Journal of neurodevelopmental disorders},
volume = {},
number = {},
pages = {},
doi = {10.1186/s11689-026-09694-0},
pmid = {42014975},
issn = {1866-1955},
support = {IDS-TILDA-2021-001/HRBI_/Health Research Board/Ireland ; IDS-TILDA-2021-001/HRBI_/Health Research Board/Ireland ; UK-20-641398//Global Brain Health Institute/ ; AS-CP-118-0020//Alzheimer's Society Fellowship/ ; NIHR203312//NIHR Cambridge Biomedical Research Centre/ ; 2022_EKEA.133//Else Kröner-Fresenius-Stiftung/ ; 2022_EKEA.133//Else Kröner-Fresenius-Stiftung/ ; 2022_EKEA.133//Else Kröner-Fresenius-Stiftung/ ; 2022_EKEA.133//Else Kröner-Fresenius-Stiftung/ ; MRC MR/S011277/1, MR/S005145/1, MR/R024901/1/MRC_/Medical Research Council/United Kingdom ; MRC MR/S011277/1, MR/S005145/1, MR/R024901/1/MRC_/Medical Research Council/United Kingdom ; 1R01AG056850-01A1, R21AG056974, R01AG061566, 1R01AG081394-01, 1R61AG066543-01/NH/NIH HHS/United States ; SLT006/17/00119//Department de Salut de la Generalitat de Catalunya/ ; IIBSP-DOW-2020-151//Fundación Tatiana Pérez de Guzmán el Bueno/ ; H2020-SC1-BHC-2018-2020//Horizon 2020-Research and Innovation Framework Programme from the European Union/ ; },
}

@article {pmid42014980,
year = {2026},
author = {Kruijff, I and van Wegen, EEH and Mul, JD and Jaspers, RT and Schrantee, A and Scherder, EJA and Lucassen, PJ and van Dam, AM},
title = {Effects of physical exercise on cognitive impairment in patients with Alzheimer's disease, Parkinson's disease or mild cognitive impairment: a systematic review and meta-analysis.},
journal = {European review of aging and physical activity : official journal of the European Group for Research into Elderly and Physical Activity},
volume = {},
number = {},
pages = {},
doi = {10.1186/s11556-026-00412-2},
pmid = {42014980},
issn = {1813-7253},
}

@article {pmid42015047,
year = {2026},
author = {Prada, D and Morava-Kozicz, E and Rajendrakumar, AL and Kupsco, A and Lesseur, C and Irizar, H and Cantú-de-Leon, D and García-Cuellar, C and Ramírez, A and González-Ruíz, J and Horowitz, CR and Cushman, M and Manly, J and Judd, S and Bagiella, E and Baccarelli, A and Parks, R},
title = {Blood mitochondrial heteroplasmic variants and cognitive performance in late midlife: REGARDS study.},
journal = {BMC neurology},
volume = {26},
number = {1},
pages = {},
pmid = {42015047},
issn = {1471-2377},
support = {U01 NS041588/AG/NIA NIH HHS/United States ; U01 NS041588/NS/NINDS NIH HHS/United States ; U54CA267776/CA/NCI NIH HHS/United States ; U01AG088684//National Institute of Aging/ ; },
}