@article {pmid41580847,
year = {2026},
author = {Goodheart, AE and Yoo, CH and Fassini, A and Dagnew, TM and Ye, R and Striar, R and Quan, M and Rattray, AK and Meyer, TN and Peterec, E and Lee, H and Fiedler, SA and Hooker, JM and Wey, HY and Wang, C and Gomperts, SN},
title = {Imaging brain class I histone deacetylase changes in the Lewy body dementias and Parkinson's disease.},
journal = {Clinical epigenetics},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13148-026-02054-8},
pmid = {41580847},
issn = {1868-7083},
abstract = {BACKGROUND: Histone deacetylases (HDACs) are epigenetic molecules responsible for regulation of gene transcription. Dysregulation of HDACs has been linked to neurodegenerative disease. Here, we used the class I HDAC PET radioligand [[11]C]Martinostat to quantify and map changes in the distribution of these molecules in the brain in dementia with Lewy bodies (DLB) and Parkinson's disease (PD). In this exploratory cross-sectional study, we acquired brain PET-MR with [[11]C]Martinostat in 14 DLB (median age 70 years (IQR 14), 21% female), 10 PD (median age 70 (8), 20% female) including four with cognitive impairment and six without, and 17 healthy control (HC) participants (median age 62 (14), 47% female). [[11]C]Martinostat uptake was compared amongst groups using whole brain voxel-wise analysis and targeted region of interest (ROI)-based approaches, adjusted for age and sex. Regional levels were also quantified in postmortem brain bank samples.

RESULTS: Compared to HC, [[11]C]Martinostat uptake in DLB was increased in precentral gyrus (ROI p = 0.044) and putamen (p < 0.001), as well as in cognitive and limbic circuitry including anterior cingulate (p = 0.042) and entorhinal cortex (p = 0.023). [[11]C]Martinostat uptake in DLB was decreased in inferior parietal cortex p < 0.001) compared to HC, consistent with prior observations in Alzheimer's disease. In PD, [[11]C]Martinostat uptake was also increased in precentral gyrus (p = 0.013), correlating with both disease duration and Hoehn and Yahr motor stage. In postmortem DLB tissue, class I HDAC levels were elevated in anterior cingulate cortex (isoform 1 p = 0.041, isoform 3 p = 0.024) and were reduced in inferior parietal cortex (isoform 1 p < 0.001).

CONCLUSIONS: The findings of this exploratory study reveal elevated levels of class I HDACs in motor cortex in PD and bidirectional changes in their regional density in the Lewy body dementias.},
}

@article {pmid41580846,
year = {2026},
author = {Faheem, MSB and Cheema, S and Raza, M and Rai, A and Abdullah, A and Asghar, T and Hassan, ST and Arshad, F and Cheema, HI and Faique, M and Samadi, S},
title = {Demographic and geographic hotspots of Alzheimer's disease and pneumonia-related mortality among older adults in the United States: a retrospective analysis.},
journal = {European journal of medical research},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40001-026-03915-x},
pmid = {41580846},
issn = {2047-783X},
abstract = {BACKGROUND: Older patients with Alzheimer's disease (AD) are more susceptible to pneumonia because of their limited mobility, malnourishment, and difficulty swallowing. This study highlights demographic and geographic while examining AD and pneumonia-related mortality rates among older adults in the United States (U.S.) between 1999 and 2023.

METHODS: Retrospective cohort research utilized mortality data from the Centre for Disease Control and Prevention's Wide-Ranging Online Data for Epidemiologic Research (CDC-WONDER). Demographic factors (age, gender, race/ethnicity) and geographic classifications (urbanization, regions, states) were examined during the analysis. We used joinpoint regression and standardization techniques to determine age-adjusted mortality rates (AAMR) and annual percentage changes (APC).

RESULTS: A total of 202,678 AD and pneumonia-related deaths were reported. Overall AAMR declined significantly from 1999 to 2023 (APC - 6.65; P < 0.05). From demographics males (22), non-Hispanic (NH) Whites (20.8), individuals aged 85 + years (98.3) had the highest mortality rates. Geographically, residents of non-metropolitan (25.6) and west regions (26.9) represented peak rates.

CONCLUSION: We observed notable demographic and geographic disparities in AD and pneumonia associated mortality, the burden of which is higher among males, NH Whites and those residing in non-metropolitan regions and therefore we emphasize the need of targeted interventions and equitable resource allocation to reduce this burden especially among high-risk populations.},
}

@article {pmid41580792,
year = {2026},
author = {Liu, X and Wei, T and Zhao, B and Zhou, S and Liu, L and Tang, Y},
title = {Surrogates of glymphatic metrics decline and coupled sleep rhythms disruption in Alzheimer's disease.},
journal = {Alzheimer's research & therapy},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13195-026-01962-4},
pmid = {41580792},
issn = {1758-9193},
support = {82220108009//National Natural Science Foundation of China/ ; JWZQ20240101023//Beijing Outstanding Young Scientist Program/ ; 2021ZD0201801//STI2030-Major Projects/ ; 2025ZD0546200//Noncommunicable Chronic Diseases-National Science and Technology Major Project/ ; },
abstract = {BACKGROUND: Sleep is essential for brain homeostasis, in part by supporting glymphatic clearance through sleep-related oscillations. However, the relationship between putative glymphatic metrics and coupled sleep rhythm disruption, and their combined role in Alzheimer's disease (AD) progression, remains poorly understood.

METHODS: We analyzed data from 75 individuals, 54 with AD and 21 cognitively normal (CN) controls, including sleep electroencephalography (EEG), magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) AD biomarkers, and two-year longitudinal cognitive assessments. Putative glymphatic metrics was evaluated using choroid plexus (CP) volume, perivascular spaces (PVSs), diffusion tensor imaging along the perivascular space (DTI-ALPS) index, and blood oxygen level-dependent signal coupled to CSF signal (BOLD-CSF coupling). Coupled sleep rhythm was assessed via slow oscillation (SO)-theta and SO-spindle couplings. Correlation and mediation analyses explored associations between these MRI-derived indices and coupled sleep oscillations, and least absolute shrinkage and selection operator (LASSO) regression was used to predict AD progression.

RESULTS: Compared to CN controls, individuals with AD had reduced DTI-ALPS index and BOLD-CSF coupling (p < 0.05), along with disrupted SO-spindle coupling (p = 0.029). Across all participants, lower global BOLD-CSF coupling correlated with misaligned SO-theta burst coupling (r = 0.311, p = 0.018), and reduced DTI-ALPS was associated with misaligned SO-spindle coupling (r = 0.370, p = 0.008). In the AD group, DTI-ALPS remained correlated with SO-spindle misalignment (r = 0.376, p = 0.028). Mediation analysis revealed that SO-spindle misalignment contributed to cognitive decline through its effect on DTI-ALPS. Importantly, combining putative glymphatic and sleep EEG metrics effectively predicted AD progression.

CONCLUSIONS: Our findings suggest that disruptions in surrogates marker of glymphatic clearance and coupled sleep rhythms are jointly associated with AD-related cognitive decline. These metrics offer a promising framework for predicting disease progression and understanding neurodegenerative mechanisms in AD.},
}

@article {pmid41580496,
year = {2026},
author = {Morris, AWJ and Mueller, RL and Sempio, C and Klawitter, J and Bryan, AD and Bidwell, LC and Hutchison, KE},
title = {Age differences in endocannabinoid tone are ameliorated after recent cannabis use.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-025-27618-1},
pmid = {41580496},
issn = {2045-2322},
support = {R01 DA039707A//This research was funded by the National Institute on Drug Abuse/ ; },
abstract = {An age-related decline in endocannabinoid system (ECS) activity may contribute to conditions such as chronic pain and Alzheimer's disease. Although cannabis is increasingly used by older adults to alleviate age-related conditions, it remains unclear how cannabinoids affect ECS activity across the lifespan. The present study assayed levels of seven endocannabinoids (AEA, 2-AG, DEA, LEA, PEA, SEA, and OEA) in a sample of adults (N = 142; younger 21-24 years, n = 38; midlife 25-54, n = 73; older 55-71, n = 31) assayed before cannabis use (baseline [pre-use]) and ~ 1 h after flower or ~ 2 h after edible cannabis use. At baseline, older adults exhibited lower AEA and DEA than younger adults, and lower LEA than midlife adults. Acute cannabis use increased AEA, DEA, LEA, PEA, SEA, and OEA across all age groups (all p < .001). 2-AG showed no increase. For AEA and DEA, increases were larger in older adults (Time×Age). These findings indicate broad endocannabinoid elevations after cannabis use regardless of age, alongside age-related differences at baseline and in acute responses.},
}

@article {pmid41580393,
year = {2026},
author = {Feiten, AF and Dahm, K and Schlepckow, K and van Lengerich, B and Suh, JH and Reifschneider, A and Wefers, B and Bartos, LM and Wind-Mark, K and de Weerd, L and Ulas, T and De-Domenico, E and Grundschöttel, P and Paulusch, S and Tast, B and Honda, T and Müller, SA and Becker, M and Khalin, I and Ricci, A and Liesz, A and Brunner, B and Krenner, C and Buschmann, K and Nuscher, B and Spieth, L and Junker, N and Berghoff, SA and Davis, SS and Neher, JJ and Wurst, W and Plesnila, N and Lewcock, JW and Simons, M and Lichtenthaler, SF and Di Paolo, G and Brendel, M and Capell, A and Monroe, KM and Schultze, JL and Haass, C},
title = {TREM2 expression level is critical for microglial state, metabolic capacity and efficacy of TREM2 agonism.},
journal = {Nature communications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41467-026-68706-8},
pmid = {41580393},
issn = {2041-1723},
support = {HA1737/16-1//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; },
abstract = {Triggering receptor expressed on myeloid cells 2 (TREM2) is a central regulator of microglial activity and loss-of-function coding variants are major risk factors for late onset Alzheimer's disease (LOAD). To better understand the molecular and functional changes associated with TREM2 signalling in microglia, we generated a TREM2 reporter mouse. In APP transgenic animals, bulk RNA-sequencing of isolated microglia sorted based on reporter expression highlighted TREM2 level-related changes in major immunometabolic pathways, and enrichment of genes in oxidative phosphorylation and cholesterol metabolism in microglia with increased TREM2 expression. Metabolic and lipidomic profiling of sorted microglia showed that, independent of Aβ pathology, TREM2 expression correlated with signatures consistent with increased cellular redox, energetics, and cholesterol homoeostasis. In accordance, metabolic activity correlated with phagocytic capacity. Finally, we performed chronic treatment with a TREM2 agonist antibody and identified a window of TREM2 expression where microglia are most responsive, thereby informing clinical applications of TREM2 agonists.},
}

@article {pmid41580241,
year = {2026},
author = {Zhang, W and Liu, H and Qian, L and Zhang, C and Wang, D and Fang, K and Chen, R and Jiao, B and Shen, L and Liao, W},
title = {Altered cerebellar morphological similarity network correlates with cognitive decline and cerebrospinal fluid biomarkers in mild Alzheimer's disease: a 7T MRI study.},
journal = {Brain research bulletin},
volume = {},
number = {},
pages = {111731},
doi = {10.1016/j.brainresbull.2026.111731},
pmid = {41580241},
issn = {1873-2747},
abstract = {BACKGROUD: Recent neuroimaging research emphasized cerebellar atrophy and alternation of functional connections in Alzheimer's disease (AD), fewer studies have focus on the cerebellar subfield and its structural network reorganization. This study aimed to explore the utility of 7T MRI in assessing cerebellar subfield volumes, morphological similarity network (MSN) and their correlation with cognitive decline and cerebrospinal fluid (CSF) biomarkers in mild AD.

METHODS: Cerebellar subfield segmentation and individual level MSNs construction were performed using high-resolution structural 7T MRI data in 30 AD of mild stage and 30 healthy normal controls (NCs). Subfield volumes and topological parameters of the resulting graphs were compared between groups. Correlations between altered MSN metrics and cognitive measurement, CSF biomarkers were further analyzed in AD group.

RESULTS: Compared to NCs, AD patients exhibited salient vermis VIIb and vermis VIIIa atrophy and significantly large-scale topological alterations of nodal properties of cerebellar MSN, predominantly in the posterior lobes (lobe VI-IX). The global network metrics were relatively preserved, despite the increased global assortativity. Altered structural network properties of lobule VIII, vermis IX and crus II were significantly associated with cognitive decline and CSF Aβ42 and p-tau181 levels in AD.

CONCLUSIONS: Our study emphasizes the crucial role of alterations in morphological connectivity beyond cerebellar atrophy in early AD using 7T MRI. Structural network alterations in lobule VIII, vermis IX and crus II demonstrated significantly correlation with clinical variables, indicating their potential as sensitive imaging markers and therapeutic targets for AD.},
}

@article {pmid41580180,
year = {2026},
author = {Jayaswamy, PK and Ambrish, T and Sangamesh, VC and Kellarai, A and Patil, P and Alexander, LM and Shetty, P},
title = {Butyrate antagonizes Annexin A2-mediated tauopathy via Annexin A1 reciprocity in Alzheimer's disease.},
journal = {Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association},
volume = {},
number = {},
pages = {115968},
doi = {10.1016/j.fct.2026.115968},
pmid = {41580180},
issn = {1873-6351},
abstract = {BACKGROUND: The balance between Annexin A1 (AnxA1), a pro-resolving mediator, and Annexin A2 (AnxA2), a pro-inflammatory counterpart, is essential for immune homeostasis but remains poorly explored in Alzheimer's disease (AD).

AIM: To evaluate butyrate's ability to restore AnxA1/AnxA2 equilibrium and attenuate tauopathy and neuroinflammation in cellular and aluminum chloride (AlCl3)/D-galactose AD models.

METHODS: In vitro, BV2 cells were used to study AnxA1/AnxA2 reciprocity in microglia, while retinoic acid-differentiated C6 cells with a neuron-like phenotype were employed to assess tau phosphorylation and AnxA1/AnxA2 interplay. In vivo, AlCl3/D-galactose rats underwent behavioral testing, Western blotting, ELISA, and immunohistochemistry evaluating butyrate's effects on annexin balance, tau pathology, redox homeostasis, and acetylcholinesterase activity.

RESULTS: In vitro, Aβ1-42 suppressed AnxA1 and elevated AnxA2 in BV2 microglia, increasing TNF-α, and promoted GSK-3α/β-driven tau phosphorylation in differentiated C6 neuron-like cells through AnxA1/AnxA2 reciprocal regulation. Butyrate restored AnxA1, suppressed AnxA2/GSK-3β/TNF-α, and attenuated tau pathology. In vivo, prophylactic butyrate preserved hippocampal cytoarchitecture, improved cognition, reduced amyloid burden, normalized redox balance, inhibited acetylcholinesterase, and re-equilibrated hippocampal/systemic AnxA1/AnxA2 with decreased p-tau.

CONCLUSION: Butyrate modulates the AnxA1/AnxA2 axis to suppress neuroinflammation and tauopathy, positioning it as a gut-brain axis therapeutic for sporadic AD.},
}

@article {pmid41580137,
year = {2026},
author = {Tien, LQ and Phung, HTT and Do, HH and Khac, TN and Minh, PTN and Linh, VNH and Thang, NQ and Wang, S and Tran, PT},
title = {Novel imidazolium salts bearing 2-oxindoles scaffold as potent acetylcholinesterase inhibitors for Alzheimer's disease: Design, synthesis, in vitro and in silico studies.},
journal = {Bioorganic & medicinal chemistry letters},
volume = {},
number = {},
pages = {130560},
doi = {10.1016/j.bmcl.2026.130560},
pmid = {41580137},
issn = {1464-3405},
abstract = {In this study, a series of thirty-five novel imidazolium salts bearing a 2-oxindoles were designed and synthesized as potent acetylcholinesterase (AChE) inhibitors for Alzheimer's disease. Structural diversity was introduced through substituent variation on both the oxindole and phenyl rings to investigate structure-activity relationships. All compounds were evaluated in vitro by the modified Ellman assay, revealing several highly potent inhibitors in the nanomolar to subnanomolar range. The most active compound, 32, exhibited an IC50 of 0.17 nM, surpassing galantamine and donepezil. Enzyme kinetic study indicated that all compounds act as mixed-type AChE inhibitors. Machine learning-based binding affinity predictions (ΔGML = -10.30 to -8.18 kcal/mol) correlated well with experimental activity. Molecular docking against AChE (PDB ID: 4EY6 and 7E3H) revealed that compounds bearing electron-withdrawing substituents exhibited superior binding scores and favorable interactions with key catalytic residues and aromatic residues. Molecular dynamics (200 ns) simulations demonstrated that compound 32 maintained a highly stable conformation within the AChE active site, with consistent hydrogen bonding and low root-mean-square deviation (RMSD) fluctuations. In addition, MM-PBSA binding free energy analysis (ΔGtotal = -33.42 kcal/mol) further confirmed its strong and stable interactions compared with galantamine (-17.82 kcal/mol) and donepezil (-21.20 kcal/mol). Furthermore, in silico ADME predictions suggested favorable oral absorption and potential blood-brain barrier permeability for compound 32, while maintaining an acceptable safety profile compared to galantamine and donepezil. These promising findings highlight the potential of oxindole-imidazolium hybrids as effective AChE inhibitors and warrant further investigation for the development of novel anti-Alzheimer agents.},
}

@article {pmid41579998,
year = {2026},
author = {Patel, R and Mewada, S and Shukla, S and Bhattacharya, S and Alsaidan, OA and Prajapati, B},
title = {Carboxymethyl chitosan for neurological drug delivery: Current trends and future prospects.},
journal = {International journal of biological macromolecules},
volume = {},
number = {},
pages = {150488},
doi = {10.1016/j.ijbiomac.2026.150488},
pmid = {41579998},
issn = {1879-0003},
abstract = {The complexity of drug delivery across the blood-brain barrier (BBB) makes disorders of the central nervous system (CNS), such as Alzheimer's disease, Parkinson's disease(PD), brain tumors, and other neurodegenerative conditions, a growing global health burden. Poor brain bioavailability and systemic side effects are common problems with traditional therapies. Delivery systems based on nanotechnology have shown promise as solutions to these problems. These include carboxymethyl chitosan (CMC), a water-soluble, biocompatible, and biodegradable chitosan derivative that has drawn a lot of interest because of its increased stability, mucoadhesiveness, improved solubility at physiological pH, and ability to encapsulate and release targeted drugs. CMC-based nanocarriers are perfect for treating a variety of conditions because they have shown promise in increasing therapeutic efficacy while reducing toxicity. Recently developed CMC-based drug delivery systems for CNS disorders are examined critically in this review, with an emphasis on their design, biological performance, targeting techniques, and potential for clinical translation in the future. Their multifunctional qualities, in vitro and in vivo evidence, and their function in regulating neuroinflammation, oxidative stress, and neuronal regeneration are given particular attention.},
}

@article {pmid41579987,
year = {2026},
author = {Jeon, YN and Baek, JS},
title = {TPGS-coated zein nanoparticles encapsulating Haematococcus pluvialis extract for Alzheimer's disease: An in vitro evaluation towards brain-targeted delivery.},
journal = {International journal of biological macromolecules},
volume = {},
number = {},
pages = {150378},
doi = {10.1016/j.ijbiomac.2026.150378},
pmid = {41579987},
issn = {1879-0003},
abstract = {Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by β-amyloid (Aβ) aggregation and limited treatment efficacy due to the restrictive nature of the blood-brain barrier (BBB). To address this, we developed d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS)-coated Zein nanoparticles (Hp-Zein-TPGS NPs) encapsulating Haematococcus pluvialis (Hp) extract as a brain-targeted drug delivery system. Hp-Zein-TPGS NPs exhibited high physical stability over 14 days, sustained astaxanthin release, and potent antioxidant activity. The NPs also demonstrated excellent biocompatibility, showing minimal cytotoxicity in both bEnd.3 and SH-SY5Y cells, along with enhanced cellular uptake in vitro. Based on the reported effects of TPGS on P-glycoprotein (P-gp) inhibition and membrane fluidity, a delivery strategy was designed to facilitate BBB transport. In an in vitro BBB model, Hp-Zein-TPGS NPs exhibited increased transport, and Rhodamine 123 (Rh123) accumulation analysis indicated properties associated with the regulation of P-gp mediated efflux. In addition, Thioflavin T (ThT) fluorescence and morphological analyses confirmed that Hp-Zein-TPGS NPs effectively inhibited Aβ1-42 aggregation and fibril formation, while WST and Annexin V-FITC/PI assays demonstrated that Hp-Zein-TPGS NPs significantly attenuated Aβ1-42-induced neuronal toxicity, indicating their neuroprotective effects. Taken together, these findings suggest that Hp-Zein-TPGS NPs possess favorable stability, biocompatibility, BBB transport potential, and neuroprotective effects, highlighting their promise as a nanocarrier system for brain-targeted therapeutic delivery in AD.},
}

@article {pmid41579928,
year = {2026},
author = {Zhou, L and Wang, Z and Jiang, Y and Wang, M and Li, X and Ren, Q},
title = {A Mendelian randomization study with bioinformatics analysis reveals gut microbiota mediates in heart failure and Alzheimer's disease via BAFF-R.},
journal = {Neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.neuroscience.2026.01.021},
pmid = {41579928},
issn = {1873-7544},
abstract = {BACKGROUND: The causal relationship between heart failure (HF) and Alzheimer's Disease (AD) is still debated, and the mechanisms underlying AD caused by HF are still not fully understood.

METHODS: This study aimed to explore the potential genetic causality between HF and AD using two-sample Mendelian randomization (MR) study. The investigation was extended with mediation MR to explore the underlying genetic mechanisms. Bioinformatics analysis provided additional evidence.

RESULTS: In our investigation, we harnessed a two-sample MR method to delineate a causal relationship between HF and AD, uncovering a significant positive association. Our results, derived from a meticulous two-step MR analysis, have shed new light on the mediating role of gut microbiota (GM) within the HF-AD interplay. Notably, we identified specific metabolic pathways with substantial correlations: a pivotal super-pathway crucial for the biosynthesis of branched chain amino acids (BCAAs) and the pyrimidine deoxyribonucleotides de novo biosynthesis II pathway. Our findings extend beyond the metabolic, revealing the 'BAFF-R on CD20-' immune cells as key mediators in the GM-AD pathway. Bioinformatics analysis revealed significant enrichment of common differentially expressed genes between HF and AD in immune-related pathways.

CONCLUSIONS: We present a thorough genetic analysis of the relationship between HF, AD, and the intestinal-neuroimmune interaction, emphasizing the potential of GM and immune cells as therapeutic targets.},
}

@article {pmid41579901,
year = {2026},
author = {Tariot, PN and Lopera, FS and Ríos-Romenets, S and Sink, KM and Giraldo-Chica, M and Acosta-Baena, N and Villegas, G and Espinosa, A and Castaño, ML and Muñoz, C and Ospina, P and Bocanegra, Y and Tirado, V and Henao, E and Cardona, E and Luna, E and Lopez, H and Sánchez, G and Collazos, MM and Alvarez, S and Aguillón, D and Hu, N and Clayton, D and Bittner, T and Schneider, A and Dolton, M and Poon, V and Nguyen, J and Thomas, RG and Schneider, LS and Chen, K and Su, Y and Alexander, RC and Quiroz, YT and Cai, Y and Xu, YR and Ostaszewski, B and Selkoe, DJ and Ashton, NJ and Denkinger, MN and Jakimovich, LJ and Doody, RS and Langbaum, JB and Reiman, EM},
title = {Safety and efficacy of crenezumab in cognitively unimpaired carriers of the PSEN1[Glu280Ala] mutation at risk for autosomal-dominant Alzheimer's disease in Colombia (API ADAD Colombia Trial): a phase 2, randomised, double-blind, placebo-controlled trial.},
journal = {The Lancet. Neurology},
volume = {25},
number = {2},
pages = {147-159},
doi = {10.1016/S1474-4422(25)00426-0},
pmid = {41579901},
issn = {1474-4465},
mesh = {Humans ; *Alzheimer Disease/genetics/drug therapy ; Double-Blind Method ; Male ; *Presenilin-1/genetics ; Female ; Middle Aged ; *Antibodies, Monoclonal, Humanized/therapeutic use/adverse effects ; Colombia ; Adult ; Mutation/genetics ; Heterozygote ; Treatment Outcome ; },
abstract = {BACKGROUND: To have maximal benefit, Alzheimer's disease-modifying treatments might need to be started before the onset of clinical symptoms. Mutations of the PSEN1 gene are inherited as fully penetrant, autosomal-dominant traits, which almost always result in the clinical onset of Alzheimer's disease before the age of 65 years. We aimed to evaluate the efficacy, including possible delayed emergence of cognitive impairment, and safety of crenezumab, an anti-amyloid monoclonal antibody, in cognitively unimpaired carriers of the PSEN1[Glu280Ala] mutation at high imminent risk of developing symptoms due to Alzheimer's disease.

METHODS: This 5-8-year common-close, double-blind, placebo-controlled, single-centre trial screened kindred members aged 30-60 years from the main health-care site in Medellín, Colombia. Participants who were cognitively unimpaired and carried the PSEN1[Glu280Ala] autosomal-dominant mutation were randomly assigned 1:1 to receive placebo or subcutaneous crenezumab (investigators and participants were masked to treatment allocation), with an initial 300 mg dose every 2 weeks that increased to 720 mg every 2 weeks, and a later optional increase to 60 mg/kg intravenously every 4 weeks. Randomisation was stratified by age, education, APOE ɛ4 carrier status, and baseline Clinical Dementia Rating. Mutation non-carriers received placebo and were included in a 1:2 ratio of non-carriers to carriers to maintain genotype masking and include a genetic kindred control. Dual primary outcomes were the annualised rates of change in the Alzheimer's Prevention Initiative (API) preclinical autosomal-dominant Alzheimer's disease (ADAD) composite test total score and Free and Cued Selective Reminding Test-Cueing Index (FCSRT-CI) assessed in randomised participants who received at least one dose of the study drug, according to treatment assignment. Primary endpoints were assessed with a random coefficient regression model with a missing-at-random assumption adjusting for randomisation factors. Safety endpoints for mutation carriers were assessed in randomised participants who received at least one dose of the study drug. This trial is registered with ClinicalTrials.gov (NCT01998841) and is completed.

FINDINGS: 619 Colombian API registrants were prescreened, 315 were assessed for eligibility, and 252 were enrolled (crenezumab-carrier, n=85; placebo-carrier, n=84; placebo-non-carrier, n=83; 160 [63%] women and 92 [37%] men) between Dec 20, 2013, and Feb 27, 2017. 237 (94%) completed the trial, with final data collection on March 22, 2022. The annualised rate of change in the API ADAD composite was -1·10 (SE 0·29) in the crenezumab group and -1·43 (0·29) in the placebo group (between-group difference 0·33 [95% CI -0·48 to 1·13]; p=0·43). The annualised rate of change in FCSRT-CI was -0·03 (0·00) in the crenezumab group and -0·04 (0·00) in the placebo group (between-group difference 0·01 [0·00 to 0·02]; p=0·16). All participants had at least one adverse event; serious adverse events occurred in 23 (27%) of 84 in the crenezumab group and 21 (25%) of 84 in the placebo group. No fatalities occurred.

INTERPRETATION: Crenezumab therapy administered for 5-8 years did not result in significant benefits on our primary clinical outcomes in cognitively unimpaired participants predisposed to developing ADAD dementia; secondary and exploratory outcomes also showed no significant effect on removal of amyloid plaques or other clinical or biomarker outcomes. Together with the results of other anti-amyloid β trials, robust fibrillar amyloid removal appears necessary for clinical efficacy in people with elevated brain amyloid. This study will further inform the biomarker, cognitive, and clinical trajectory of preclinical ADAD, the risk of clinical progression in amyloid-positive and amyloid-negative mutation carriers, and the size and design of future secondary and primary prevention trials.

FUNDING: US National Institute on Aging (NIA), Banner Alzheimer's Institute, Genentech, F Hoffmann-La Roche.},
}

Humans
*Alzheimer Disease/genetics/drug therapy
Double-Blind Method
Male
*Presenilin-1/genetics
Female
Middle Aged
*Antibodies, Monoclonal, Humanized/therapeutic use/adverse effects
Colombia
Adult
Mutation/genetics
Heterozygote
Treatment Outcome

@article {pmid41579884,
year = {2026},
author = {Fortea, J and Llibre-Guerra, J and O'Connor, A and Levin, J},
title = {Lessons from the Colombian kindred: rethinking Alzheimer's prevention.},
journal = {The Lancet. Neurology},
volume = {25},
number = {2},
pages = {117-119},
doi = {10.1016/S1474-4422(25)00481-8},
pmid = {41579884},
issn = {1474-4465},
}

@article {pmid41579747,
year = {2026},
author = {Cipriani, GE and Borghesi, F and Cipresso, P and Canessa, N and Molfese, S and Manco, C and Chirico, A and Simoncini, G and Anselmino, M and Amanzio, M},
title = {Cognitive changes and emotional heart rate variability dynamics in subjective cognitive decline: An exploratory longitudinal neuropsychophysiological study.},
journal = {Acta psychologica},
volume = {263},
number = {},
pages = {106308},
doi = {10.1016/j.actpsy.2026.106308},
pmid = {41579747},
issn = {1873-6297},
abstract = {Subjective cognitive decline (SCD) is increasingly recognised as a potential preclinical stage of Alzheimer's disease, yet the physiological mechanisms underlying its progression remain poorly understood. This longitudinal study examined whether heart rate variability (HRV), a non-invasive marker of autonomic nervous system regulation, could serve as an early psychophysiological indicator of cognitive vulnerability in older adults with SCD. Twenty-one participants meeting established SCD criteria completed two identical experimental sessions approximately 12 months apart. Each session included comprehensive neuropsychological testing and continuous HRV recording during exposure to emotionally evocative images from the International Affective Picture System, presented in a temporally extended and affectively rich paradigm known as an "affective storm". At the group level, no significant changes in cognitive performance or HRV indices were observed over time. However, analyses of individual change scores revealed that longitudinal variations in HRV, particularly in indices reflecting parasympathetic tone and overall autonomic flexibility, were selectively and consistently associated with performance in global cognition, verbal fluency, and visuospatial working memory. These findings suggest that dynamic autonomic responses to emotional stimulation may reflect subtle physiological correlates of cognitive functioning, even in the absence of overt cognitive decline. The observed associations are consistent with neurovisceral integration models, and support the potential utility of HRV as a sensitive, non-invasive marker of early cognitive trajectories in ageing. In conclusion, HRV may offer unique insights into the complex interaction between emotional reactivity and cognitive resilience in older adults with SCD, opening promising avenues for early screening and intervention.},
}

@article {pmid41579660,
year = {2026},
author = {Vos-Draper, T and Jordan, K and Morrow, M and Udulutch, E and Sonenblum, SE},
title = {Monitoring of wheelchair use in long-term memory care units.},
journal = {Geriatric nursing (New York, N.Y.)},
volume = {69},
number = {},
pages = {103808},
doi = {10.1016/j.gerinurse.2026.103808},
pmid = {41579660},
issn = {1528-3984},
abstract = {Residents in long term care (LTC) with Alzheimer's disease (AD) or related dementias (ADRD) who require wheelchairs to accommodate impaired mobility experience increased risk of falls and sitting-related pressure injuries (PrIs). Addressing that risk requires a multifactorial approach and strategic prioritization of care needs. Objective data about patterns of wheelchair use, including timing of transfers and overall time in chair could inform decisions about strategies to reduce fall or pressure injury risk. This pilot feasibility study used passive data collection from force sensors placed unobtrusively under the seat cushions on wheelchairs (n = 18) at two LTC memory care units to measure how the wheelchairs were used over 7 days. Four occupancy patterns were identified: All day (n = 6 chairs, 21 days) without transfers, One Transfer (n = 15 chairs, 41 days), Two Transfers (n = 12 chairs, 33 days), and Inconsistent (n = 3 chairs, 10 days). Wheelchair occupancy time (hours/day) in this cohort (Mean = 8.7, SD = 2.7) were lower than those of community wheelchair users and the number of daily transfers (Mean = 2.9, SD = 1.7) was also lower. With the rapidly aging U.S. population and limited care staffing, information from effective unobtrusive data collection technologies, such as the WiSAT system successfully used in this study, can potentially facilitate improved prevention of falls or pressure injuries that occur with prolonged wheelchair use in LTC facilities.},
}

@article {pmid41579487,
year = {2026},
author = {Chen, X and Zhang, X and Xiong, W and Wang, T and Jia, A and Feng, Q and Huang, M},
title = {Hippocampal surface morphological variation-based genome-wide association analysis network for biomarker detection of Alzheimer's disease.},
journal = {Medical image analysis},
volume = {110},
number = {},
pages = {103952},
doi = {10.1016/j.media.2026.103952},
pmid = {41579487},
issn = {1361-8423},
abstract = {Performing genome-wide association analysis (GWAS) between hippocampus and whole-genome data can facilitate disease-related biomarker detection of Alzheimer's disease (AD). However, most existing studies have prioritized hippocampal volume changes and ignored the morphological variations and subfield differences of the hippocampus in AD progression. This disregard restricts the comprehensive understanding of the associations between hippocampus and whole-genome data, which may result in some potentially specific biomarkers of AD being missed. Moreover, the representation of the complex associations between ultra-high-dimensional imaging and whole-genome data remains an unresolved problem in GWAS. To address these issues, we propose an end-to-end hippocampal surface morphological variation-based genome-wide association analysis network (HSM-GWAS) to explore the nonlinear associations between hippocampal surface morphological variations and whole-genome data for AD-related biomarker detection. First, a multi-modality feature extraction module that includes a graph convolution network and an improved diet network is presented to extract imaging and genetic features from non-Euclidean hippocampal surface and whole-genome data, respectively. Second, a dual contrastive learning-based association analysis module is introduced to map and align genetic features to imaging features, thus narrowing the gap between these features and helping explore the complex associations between hippocampal and whole-genome data. Last, a dual cross-attention fusion module is applied to combine imaging and genetic features for disease diagnosis and biomarker detection of AD. Extensive experiments on the real Alzheimer's Disease Neuroimaging Initiative dataset and simulated data demonstrate that HSM-GWAS considerably improves biomarker detection and disease diagnosis. These findings highlight the ability of HSM-GWAS to discover disease-related biomarkers, suggesting its potential to provide new insights into pathological mechanisms and aid in AD diagnosis. The codes are to be made publicly available at https://github.com/Meiyan88/HSM-GWAS.},
}

@article {pmid41579459,
year = {2026},
author = {Mirjan, N and Zecevic, A and Shoemaker, L},
title = {Mapping assistive technologies along the progression of Alzheimer's disease: A scoping review.},
journal = {Archives of gerontology and geriatrics},
volume = {143},
number = {},
pages = {106142},
doi = {10.1016/j.archger.2026.106142},
pmid = {41579459},
issn = {1872-6976},
abstract = {BACKGROUND AND OBJECTIVES: A growing population of people living with Alzheimer's Disease requires improved supports for aging in place. Assistive technologies (ATs) can delay institutionalization, reduce care partner strain, and improve quality of life for this population. The abilities and needs of this population change during disease progression, but it remains unclear which ATs are best suited for specific stages. The purpose of this scoping review was to provide a snapshot in time by mapping currently available ATs assessed in peer-reviewed research, across the seven stages of Alzheimer's Disease progression.

RESEARCH DESIGN AND METHODS: The review followed the Arksey and O'Malley framework to identify and harvest information from Medline, Scopus, CINAHL, and Embase databases. Inclusion criteria were Alzheimer's Disease, technology interventions of any type and duration, English language, and the period between 2000 and 2023. Data was extracted and analyzed using six predetermined domains of ATs for dementia: safety devices, clinical devices, memory aids, ATs for preventing social isolation, ATs for leisure activities, and ATs for supporting everyday tasks.

RESULTS: A total of 87 ATs, reported in 47 articles, were mapped along seven stages of the disease. A variety of ATs are available, with high technology (e.g., tracking devices) targeting initial stages, and low technology (e.g., weighted blanket) targeting later stages. Music therapies were present across all disease stages.

DISCUSSION AND IMPLICATIONS: The map has the potential to inform people with Alzheimer's Disease, care partners, technology companies, policy makers and service providers on current AT availability and need for further development.},
}

@article {pmid41579116,
year = {2026},
author = {Karim, MRU and Haque, S and Islam, M and Higgins, C and Selim, M and Sardar, MN and Du, D},
title = {Pyrimidine RNA Homopolymers Promote Amyloid Formation of a Tau Fragment from the Microtubule-Binding Domain.},
journal = {The journal of physical chemistry. B},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.jpcb.5c07284},
pmid = {41579116},
issn = {1520-5207},
abstract = {Abnormal aggregation of microtubule-associated protein tau into β-sheet-rich fibrils is a hallmark feature of Alzheimer's disease and other tauopathies. The pathogenic P301L mutation within the microtubule-binding domain of tau promotes tau filament formation; however, the molecular mechanisms by which intracellular RNAs regulate this aggregation process remain not fully understood. Here, we investigated the mechanistic effects of RNA homopolymers on the aggregation of a tau fragment peptide (residues 298-317) derived from the microtubule-binding region and its P301L mutant. The results showed that while the wild-type peptide remained resistant to aggregation in the presence of RNA, pyrimidine-rich RNAs (poly(C) and poly(U)) significantly accelerated fibrillation of the P301L mutant. The mutation likely disrupts the local conformational constraints, leading to a more flexible conformation and exposure of hydrophobic residues. This facilitates intermolecular interactions to form β-sheet-rich aggregates after RNA-induced local condensation and alignment of the peptide as a nucleation scaffold for aggregation. In contrast, purine-rich RNAs (poly(A) and poly(G)) had negligible effects on P301L mutant aggregation, suggesting that the specific chemical and conformational properties of RNA, such as base structures, geometrical arrangement, and base stacking, in addition to its polyanionic nature, are critical determinants of its ability to modulate tau peptide amyloid formation. Furthermore, the polycationic molecules spermine and polyarginine effectively delayed or inhibited RNA-induced aggregation, indicating that rationally designed polycations could serve as valuable modulators of RNA-mediated fibrillation within the crucial tau aggregation-prone region.},
}

@article {pmid41578894,
year = {2026},
author = {Maboudian, SA and Fonseca, CS and Martersteck, AC and Chao, Y and Chen, Y and Ushizima, D and Tosun, D and Grinberg, LT and Weiner, KS and Jagust, WJ and , },
title = {Tau Pathology in Alzheimer's Disease Uniquely Affects Sulcal Depths.},
journal = {Annals of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1002/ana.78166},
pmid = {41578894},
issn = {1531-8249},
abstract = {OBJECTIVE: Though it is widely known that tau deposition affects brain structure, the precise localization of these effects is poorly understood, especially in relation to gyral and sulcal anatomy. We investigated whether tau pathology in Alzheimer's disease (AD) preferentially affects sulci, and particularly sulcal depths.

METHODS: We analyzed 675 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) with magnetic resonance imaging (MRI) and positron emission tomography (PET) data to investigate relationships between neocortical tau PET signal and cortical thickness. We then examined an advanced AD case with postmortem MRI and coregistered whole-brain phospho-tau staining for evidence of sulcal tau distribution in AD. Finally, in a sample of 187 cognitively unimpaired young and older adults with resting-state functional MRI, we examined connectivity strength between tau-vulnerable regions and the hippocampus across adulthood, prior to disease-related cognitive decline.

RESULTS: Our findings revealed that tau-related cortical thinning predominantly occurs in sulcal regions, especially the deepest parts. Postmortem histology confirmed preferential tau accumulation in sulcal depths. Additionally, connectivity analyses revealed that, across adulthood, these primarily sulcal regions most susceptible to tau-related thinning also have stronger connectivity to the hippocampus, suggesting a role for network connectivity in the vulnerability of sulci to the effects of tau pathology later in life.

INTERPRETATION: These findings support the hypothesis that sulci, and particularly their depths, represent structurally and functionally vulnerable regions for tau deposition in AD. Understanding the mechanisms underlying this sulcal vulnerability provides insight into general principles driving regional susceptibility to pathology, and sheds light on the detrimental functional and cognitive effects of tau pathology. ANN NEUROL 2026.},
}

@article {pmid41578612,
year = {2026},
author = {},
title = {Novel Protein Networks and Key Drivers of Alzheimer's Disease.},
journal = {The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry},
volume = {32},
number = {1},
pages = {5},
doi = {10.1177/10738584251413540},
pmid = {41578612},
issn = {1089-4098},
}

@article {pmid41578558,
year = {2026},
author = {Li, Z and Xiu, W and Duan, J and Zhang, Y and Dou, X and Zhang, J and Sheng, G and Liu, Y},
title = {Dementia burden among women in China: A cross-national comparative analysis with the United States and Japan using GBD 2021.},
journal = {Medicine},
volume = {105},
number = {4},
pages = {e47361},
doi = {10.1097/MD.0000000000047361},
pmid = {41578558},
issn = {1536-5964},
mesh = {Humans ; Female ; United States/epidemiology ; Japan/epidemiology ; China/epidemiology ; Aged ; Middle Aged ; Prevalence ; *Dementia/epidemiology/mortality ; Aged, 80 and over ; Adult ; Disability-Adjusted Life Years ; Cost of Illness ; Alzheimer Disease/epidemiology ; },
abstract = {This study aims to quantify the burden of Alzheimer's disease and other dementias among women in China from 1990 to 2021 and compare these patterns with those in the United States and Japan, identifying drivers and informing targeted prevention and intervention strategies. We extracted dementia data for women aged ≥ 40 years in China, the United States, and Japan from the GBD 2021 database, including prevalence, mortality, and disability-adjusted life years (DALYs). Trends in age-standardized prevalence rate, age-standardized death rate, and age-standardized DALY rate from 1990 to 2021 were summarized using estimated annual percentage change (EAPC) and percent change. Factor decomposition quantified the contributions of population aging, population growth, and epidemiological change to female dementia mortality. Pearson correlation examined associations between age-standardized DALY rates and the socio-demographic index. A Bayesian age-period-cohort model projected dementia prevalence and mortality among Chinese women from 2022 to 2036. In 2021, China had 10.83 million women living with dementia and 3,28,400 dementia-related deaths. The age-standardized prevalence rate, age-standardized death rates, and age-standardized DALY rate among Chinese women were 1025.11, 33.80, and 631.38 per 1,00,000, respectively - each higher than the corresponding rates in the United States (855.19, 31.60, and 563.46 per 1,00,000) and Japan (759.99, 29.57, and 516.08 per 1,00,000). Across all 3 countries, the dementia burden among women exceeded that among men. In China, prevalence peaked at ages 75 to 79. Elevated fasting plasma glucose and high body mass index were the principal risk factors. Population growth and aging were the main drivers of rising dementia mortality among Chinese women. Projections indicate that both prevalence and mortality among Chinese women will continue to increase through 2036. The burden of dementia among women in China exceeds that in the United States and Japan and is projected to grow further. Strengthening early detection, midlife health management, and health insurance coverage, with particular attention to women's health needs, is recommended to mitigate the future burden.},
}

Humans
Female
United States/epidemiology
Japan/epidemiology
China/epidemiology
Aged
Middle Aged
Prevalence
*Dementia/epidemiology/mortality
Aged, 80 and over
Adult
Disability-Adjusted Life Years
Cost of Illness
Alzheimer Disease/epidemiology

@article {pmid41578327,
year = {2026},
author = {Lee, S and Byun, MS and Yi, D and Ahn, H and Jung, G and Jung, JH and Chang, YY and Kim, K and Choi, H and Choi, J and Lee, JY and Kang, KM and Sohn, CH and Lee, YS and Kim, YK and Lee, DY and , },
title = {BMI changes from midlife to late life and their relationship with Alzheimer's disease pathologies.},
journal = {Alzheimer's research & therapy},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13195-026-01967-z},
pmid = {41578327},
issn = {1758-9193},
support = {NRF-2014M3C7A1046042 & RS-2022-00165636//Ministry of Science and ICT, South Korea/ ; HI18C0630, HI19C0149 & HU23C0140//Ministry of Health and Welfare/ ; No. 3020200030//Seoul National University Hospital/ ; U01AG072177//National Institute of Aging, United States/ ; },
}

@article {pmid41578064,
year = {2026},
author = {Ko, J and Son, G and Seo, HE and Cho, J and Kim, JY and Lee, SY and Kim, D and Park, S and Park, KH and Lockhart, SN and Kim, DH and Noh, Y},
title = {Tau PET imaging as a mediator between glymphatic dysfunction and cognitive decline: a cross-sectional and longitudinal study.},
journal = {European journal of nuclear medicine and molecular imaging},
volume = {},
number = {},
pages = {},
pmid = {41578064},
issn = {1619-7089},
support = {RS-2024-00334574//Ministry of Health and Family Welfare/ ; RS-2021-NR060117//Ministry of Education/ ; FRD2022-16//Gil Medical Center, Gachon University/ ; FRD2025-01//Gachon University Gil Medical Center/ ; },
abstract = {PURPOSE: Impaired glymphatic function is considered an important characteristic of cognitive decline, but the role of tau pathology as a mediator remains unclear. This study investigated whether tau burden mediates the association between diffusion tensor image analysis along the perivascular space (DTI-ALPS) and cognitive impairment or brain atrophy. Also, we explored whether DTI-ALPS index predicts longitudinal cognitive deterioration over time.

METHODS: We included 144 individuals with mild cognitive impairment (MCI), Alzheimer's disease dementia (ADD), and other dementia, or normal cognition. All participants underwent 3.0-Tesla MRI, [18]F-MK6240 and [18]F-Flutemetamol PET scans, APOE genotyping, and comprehensive neuropsychological assessments. Among these, 101 were followed longitudinally for two years. Mediation analyses within a causal framework were used to investigate whether tau burden mediated the association between DTI-ALPS index and cognition function and structural MRI measures. Longitudinal associations were tested using linear mixed-effects models.

RESULTS: DTI-ALPS index was significantly lower in cognitively impaired individuals compared to cognitively normal (CN) participants. Lower DTI-ALPS index was associated with higher tau burden and worse cognitive function. Tau burden was also inversely associated with cognition. Mediation analysis indicated that tau burden accounted for approximately 21-27% of the association between DTI-ALPS and cognition. Longitudinal analysis showed baseline lower DTI-ALPS index also predicted faster longitudinal cognitive decline.

CONCLUSION: Our findings suggest that the DTI-ALPS index is an indirect marker of glymphatic dysfunction associated with tau accumulation and cognitive decline. Tau pathology may partially link compromised glymphatic clearance to cognitive impairment.},
}

@article {pmid41577863,
year = {2026},
author = {Ahamed, MS and Ahamed, A and Jim, JC and Akhter, R and Sabbir, SI and Hasan, A},
title = {Exploring Green-Synthesized Silver Nanoparticles in Neurodegeneration: a Systematic Review of Cholinesterase Enzyme Interactions.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {393},
pmid = {41577863},
issn = {1559-1182},
mesh = {*Silver/chemistry/therapeutic use/pharmacology ; *Metal Nanoparticles/chemistry/therapeutic use ; Humans ; *Green Chemistry Technology/methods ; Animals ; *Neurodegenerative Diseases/drug therapy/enzymology ; *Cholinesterase Inhibitors/pharmacology/therapeutic use ; Butyrylcholinesterase/metabolism ; *Cholinesterases/metabolism ; Acetylcholinesterase/metabolism ; },
abstract = {Neurodegenerative disorders, particularly Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD), represent a significant and growing global health concern in recent decades due to their complex pathology and lack of curative treatments. The fundamental cause of the evolution of these disorders is the dysfunction of cholinergic neurotransmission; those are mostly regulated by cholinesterase enzymes such as acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Conventional synthetic cholinesterase inhibitors like donepezil, rivastigmine, and galantamine are proposed for symptomatic relief but are often associated with adverse effects, limited bioavailability, and decreased long-term efficacy. Here, green-synthesized silver nanoparticles (AgNPs), which are derived from plant extracts and other biological systems, give an extraordinary alternative. These nanoparticles offer a biocompatible, eco-friendly, and cost-effective alternative to conventional synthetic methods. Greener AgNPs inhibit them by binding to the enzymes AChE and BChE and prevents them from breaking down neurotransmitters ACh and BCh. As a result, the count of neurotransmitters remains high in the synapse and can provide an effective synaptic transmission. Green-synthesized AgNPs can provide targeted drug delivery, enhance solubility, enhance bioavailability, improve absorption, and also be able to overcome the blood-brain barrier (BBB); all these characteristics give better therapeutic action than all conventional methods. This study evaluates the efficacy of green-synthesized silver nanoparticles in combination with several medicinal plants for treating neurodegenerative diseases, encouraging further research to upgrade these formulations for improved patient outcomes and increased clinical applicability.},
}

*Silver/chemistry/therapeutic use/pharmacology
*Metal Nanoparticles/chemistry/therapeutic use
Humans
*Green Chemistry Technology/methods
Animals
*Neurodegenerative Diseases/drug therapy/enzymology
*Cholinesterase Inhibitors/pharmacology/therapeutic use
Butyrylcholinesterase/metabolism
*Cholinesterases/metabolism
Acetylcholinesterase/metabolism

@article {pmid41577446,
year = {2026},
author = {Morin, TM and Cowan, JL and Chen, HY and Parent, JH and Crawford, JL and Ciampa, CJ and Shah, VD and Hsu, M and Jagust, WJ and Berry, AS},
title = {Alzheimer's disease pathologies affect dopaminergic neural mechanisms of memory.},
journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1523/JNEUROSCI.1580-25.2026},
pmid = {41577446},
issn = {1529-2401},
abstract = {Aging is accompanied by the disruption of multiple neural systems including alteration in dopamine neurotransmission as well as through the accumulation of neuropathology. Despite broad appreciation that complex mental function relies on integration across systems, there is a general lack of understanding of how multiple age and disease-related brain features interact to drive variation in performance. To address this gap, we used positron emission tomography in male and female humans to examine independent and combined impacts of dopamine synthesis capacity ([[18]F]Fluoro-L-m-tyrosine) and Alzheimer's disease (AD)-related pathology (amyloid-β: [[11]C]Pittsburgh Compound B; tau: [[18]F]Flortaucipir) on memory for rewarding events, which we assessed using functional magnetic resonance imaging (n = 80 young and older adults). We specifically probed dopamine synthesis capacity given evidence that it is upregulated in older age, and may impart resilience to age-related neural losses. In young adults, higher dopamine synthesis capacity was associated with superior overall memory and greater temporal lobe activation. In older adults, neither dopamine nor AD pathology independently predicted memory performance, though higher dopamine synthesis capacity was associated with memory biases for stimuli associated with rewards rather than losses. Instead, we observed interactions between dopamine synthesis and pathology whereby only older adults with minimal pathology showed preservation of positive dopamine-memory associations. In contrast to resilience accounts, the presence of AD pathology disrupted and even reversed relationships between dopamine synthesis, memory, and temporal lobe activation. These results suggest that AD pathological processes acutely alter the mechanisms by which elevated dopamine synthesis supports optimal memory performance.Significance Statement While there is compelling evidence that aging is associated with concomitant alterations in dopamine function and cognition, studies directly linking individual differences in endogenous dopamine with memory performance in older age have shown mixed results. We find that the presence of amyloid-β and tau pathology significantly alters relationships among in vivo measures of dopamine synthesis capacity, brain activity, and behavior such that episodic memory performance appears to be relatively decoupled from the dopamine system in the context of preclinical Alzheimer's disease. These findings suggest that it is critical to account for pathological disease processes when considering the mechanisms by which dopamine influences cognitive function, and have implications for understanding the efficacy of therapeutic interventions targeting the dopamine system.},
}

@article {pmid41577409,
year = {2026},
author = {Sebastian-delaCruz, M},
title = {Chemokines and their receptors: The importance of their expression for an appropriate regulation of the immune response in health and disease.},
journal = {Advances in genetics},
volume = {115},
number = {},
pages = {279-363},
doi = {10.1016/bs.adgen.2025.11.010},
pmid = {41577409},
issn = {0065-2660},
mesh = {Humans ; *Chemokines/genetics/metabolism/immunology ; *Receptors, Chemokine/genetics/metabolism/immunology ; Animals ; Leukocytes/immunology/metabolism ; Signal Transduction ; Cell Movement ; Gene Expression Regulation ; Alzheimer Disease/immunology/genetics/pathology ; Multiple Sclerosis/immunology/genetics ; },
abstract = {Leukocytes are typically migratory immune cells, and their migration is of critical immunological importance. In this context, chemokines and their receptors play a dynamic role in regulating the functions of leukocytes within the immune system, since they drive leukocytes into and out of blood and lymphatic vessels and direct their interstitial movement and positioning. Chemokines constitute a large family of cytokines that primarily regulate immune cell migration through the binding to chemokine receptors expressed on the surface of leukocytes. They are expressed by both immune and non-immune cells, and their activity is tightly regulated at several levels from transcription to secretion and distribution. Conventional chemokine receptors are G protein-coupled receptors (GPCR) found mainly in immune cells that can modulate the immune response activation by the initiation of a signaling cascade. On the contrary, atypical chemokine receptors act as decoy receptors and regulate chemokine levels in the blood. Together, chemokines and their receptors form the chemokine system, a complex network with high redundance and promiscuity. Dysregulation of this system can contribute to various disorders that have an immune or inflammatory component mediated by chemokine-directed leukocyte migration, such as chronic inflammatory and neurodegenerative disorders. Thus, in this chapter I focused on the role of chemokines and their receptors under physiological conditions and on their implication in disorders like multiple sclerosis, Parkinson's Disease and Alzheimer's Disease, in which neuroinflammation caused by the infiltration of these immune cells into the CNS and their activation plays a key role in the development of the pathologies.},
}

Humans
*Chemokines/genetics/metabolism/immunology
*Receptors, Chemokine/genetics/metabolism/immunology
Animals
Leukocytes/immunology/metabolism
Signal Transduction
Cell Movement
Gene Expression Regulation
Alzheimer Disease/immunology/genetics/pathology
Multiple Sclerosis/immunology/genetics

@article {pmid41577113,
year = {2026},
author = {Wang, S and Wang, J and Hu, Z and Wu, L and Huang, L},
title = {Role of glycolysis-mediated histone lactylation in microglial activation and progression of neurodegenerative diseases.},
journal = {Experimental neurology},
volume = {},
number = {},
pages = {115663},
doi = {10.1016/j.expneurol.2026.115663},
pmid = {41577113},
issn = {1090-2430},
abstract = {Microglia-mediated neuroinflammation is a key driver of neurodegenerative disease progression, yet the metabolic mechanisms underlying microglial dysfunction remain poorly understood. Recent studies highlight glycolytic reprogramming in activated microglia, which generates lactate that, in turn, promotes histone lactylation, an epigenetic modification that significantly alters gene expression. This glycolysis-histone lactylation axis has been implicated in Alzheimer's disease, Parkinson's disease, and other neurodegenerative disorders, where its dysregulation exacerbates chronic neuroinflammation and neuronal damage. Despite this, the precise molecular mechanisms linking microglial metabolic shifts to epigenetic remodeling and disease pathogenesis are not fully defined. This review consolidates current knowledge on how the glycolysis-histone lactylation pathway influences microglial phenotypes and function in neurodegenerative contexts. We explore the molecular machinery driving lactate-mediated histone modifications, their transcriptional consequences, and their pathological impact on disease progression. Importantly, we discuss emerging therapeutic strategies targeting this metabolic-epigenetic axis, including glycolysis inhibitors and lactylation modulators, as promising precision medicine approaches for neurodegenerative diseases. By elucidating these mechanisms, this review provides a framework for developing metabolism-based interventions aimed at restoring microglial homeostasis and slowing neurodegeneration.},
}

@article {pmid41577051,
year = {2026},
author = {Badal, R and Kaur, B and Singh, H and Sharma, P and Yadav, P and Mahapatra, A and Ghildiyal, S and Patel, AK and Kumar, L and Sharma, B and Prajapati, PK and Nesari, T},
title = {Saraswata Ghrita mitigates AlCl3- and D-galactose-induced cognitive deficits in a murine Alzheimer's-like model: in silico and in vivo insights.},
journal = {Brain research bulletin},
volume = {},
number = {},
pages = {111742},
doi = {10.1016/j.brainresbull.2026.111742},
pmid = {41577051},
issn = {1873-2747},
abstract = {BACKGROUND: Alzheimer's disease (AD) is characterized by cognitive decline linked to cholinergic dysfunction, oxidative stress, and neuroinflammation. Saraswata Ghrita (SG), a classical Ayurvedic formulation, was evaluated using an integrated in silico-in vivo workflow focusing on acetylcholinesterase (AChE) and related pathways.

METHODS: SG constituents were profiled by GC-MS/MS and HR-LCMS/MS-QTOF. BBB-permeable, drug-like candidates were prioritized (SwissADME/BOILED-Egg) and evaluated by docking and molecular dynamics. In vivo, mice received AlCl₃ (4mg/kg, i.p.) + D-galactose (50mg/kg, i.p.) for 60 days; SG (3, 6, 12mL/kg, p.o.) or donepezil (0.5mg/kg, i.p.) was administered on days 31-60. Behavioral, biochemical, and histological endpoints were assessed (n = 6/group).

RESULTS: In silico, LIG_91 showed the top predicted AChE binding affinity (-8.5kcal·mol⁻¹) and LIG_212 scored -7.8kcal·mol⁻¹ (supportive evidence). AlCl₃+D-galactose impaired cognition (MWM day-4 ELT 85.8 ± 5.3s; TSTQ 34.6 ± 2.2s). SG 12mL/kg improved MWM performance (ELT 44.1 ± 3.2s, ~49% lower vs model; TSTQ 50.1 ± 2.8s, ~45%higher), while donepezil produced greater improvement (ELT 26.7 ± 2.4s, ~69% lower; TSTQ 58.1 ± 5.4s, ~68%higher). SG 12mL/kg reduced oxidative stress (TBARS 12.93 ± 1.58 → 8.84 ± 0.52nM/mg, ~32% decrease) and improved antioxidant status (GSH 7.52 ± 0.48 → 11.10 ± 0.48µM/mg, ~48% increase). SG also attenuated neuroinflammation (IL-6 211.1 ± 10.6 → 165.0 ± 23.6pg/mL, ~22% decrease; TNF-α 179.3 ± 8.7 → 133.7 ± 7.8pg/mL, ~25% decrease; IL-10 12.3 ± 1.0 → 30.2 ± 5.2pg/mL, ~146% increase) and lowered AChE activity (10.61 ± 0.61 → 8.49 ± 0.49µM/min/mg, ~20% decrease). H&E micrographs qualitatively suggested reduced cortical neuronal degeneration.

CONCLUSIONS: SG administration was associated with improved cognition and partial normalization of cholinergic, oxidative, and inflammatory markers in this model. Computational findings support possible AChE engagement but are not definitive; further quantitative histology and standardized-formulation studies are warranted.},
}

@article {pmid41576952,
year = {2026},
author = {Li, X and Tang, X and Zeng, J and Duan, L and Hou, Z and Li, L and Guo, Y and Chai, C and Liu, J and Wang, Y and Zhu, LQ and Li, H and Zhang, T and Wang, Y and He, A and Lu, Y},
title = {Peripheral cancer attenuates amyloid pathology in Alzheimer's disease via cystatin-c activation of TREM2.},
journal = {Cell},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.cell.2025.12.020},
pmid = {41576952},
issn = {1097-4172},
abstract = {Alzheimer's disease (AD) and cancer are among the most devastating diseases worldwide. Epidemiological data indicate that the incidence of AD significantly decreases in patients with a history of cancer. However, whether and how peripheral cancer may affect AD progression is yet to be studied. Here, we find that peripheral cancer inhibits amyloid pathology and rescues cognition via secretion of cystatin-c (Cyst-C), which binds amyloid oligomers and activates triggering receptor expressed on myeloid cells 2 (TREM2) in microglia, enabling microglia to degrade the pre-existing amyloid plaques in AD mice. These effects of Cyst-C are abolished by a cell-type-specific deletion (Cx3cr1[TREM2-/-]) or mutation of TREM2 (TREM2[R47H]) or Cyst-C (Cyst-C[L68Q]) in microglia. Together, these findings provide significant conceptual advances into cancer neuroscience and establish therapeutic avenues that are distinct from the present amyloid-lowering strategies, aiming at degrading the existing amyloid plaques for precision-targeted AD therapy.},
}

@article {pmid41576905,
year = {2026},
author = {Issa, S and Wang, Q and Qi, R and Peng, G and Yin, S and Peng, Q},
title = {An effective alzheimer disease diagnosis using resting state fmri images and broad learning system.},
journal = {Psychiatry research. Neuroimaging},
volume = {357},
number = {},
pages = {112133},
doi = {10.1016/j.pscychresns.2025.112133},
pmid = {41576905},
issn = {1872-7506},
abstract = {In this paper, a new multiclass Alzheimer diagnosis system is proposed using Broad Learning (BL) and the combination of Local Coherence (LCOR) and Intrinsic Connectivity Contrast (ICC) parameters. A public resting state fMRI database; including healthy elderly subjects (HC), Alzheimer Disease (AD) and Mild Cognitive Impairment (MCI) patients; was chosen in this study. All rs-fMRI pre-processing and analysis were performed by CONN toolbox. Three contrast cases of AD, MCI and HC were implemented within the group-level analysis, then both LCOR and ICC parameters of the effected brain clusters were combined and collected. For diagnosis system, Broad Learning (BL) classifier is trained to classify three stages of AD, MCI and HC, respectively. Referring to the experimental results and compared with other current studies, the proposed system achieved high average accuracy of 99.6% with low training time of 2 s. Furthermore, a mapping between effected brain regions and their functions is given to interprets the common symptoms for AD and MCI patients.},
}

@article {pmid41576571,
year = {2026},
author = {McPhillips, MV and Donnelly, E and Dong, F and Petrovsky, DV and Sefcik, JS and Brewster, GS and Li, J and Gooneratne, NS and Hodgson, NA},
title = {Caregiver outcomes related to sleep disturbances in persons living with cognitive impairment.},
journal = {Geriatric nursing (New York, N.Y.)},
volume = {68},
number = {},
pages = {103869},
doi = {10.1016/j.gerinurse.2026.103869},
pmid = {41576571},
issn = {1528-3984},
abstract = {Sleep disturbances in persons living with cognitive impairment (PLWCI) may impose a great burden on caregivers. We examined the association between sleep (objective sleep quality and quantity; subjective sleep impairment, quality, and daytime sleepiness) in PLWCI and caregiver depression, mastery, and burden via secondary analysis of Healthy Patterns baseline data (n = 209). Objective sleep variables included total sleep time and sleep efficiency derived from PLWCI using 3 nights of actigraphy. Subjective sleep measures included PROMIS Sleep Related Impairment, Pittsburgh Sleep Quality Index, and Epworth Sleepiness Scale, filled out by the caregiver describing the PLWCI sleep. Caregiver measures included Center for Epidemiological Studies Depression Scale, Caregiver Mastery Scale and Zarit Burden Interview. PLWCI were primarily female (66.5%) and Black (64%), with a mean age of 73.6 ± 8.6. Caregivers were mainly female (81%) and family caregivers (67%), with a mean age of 56.6 ± 14.7. After controlling for PLWCI cognition, age, and gender, poorer PLWCI sleep quality was significantly associated with more caregiver depression (β = 0.387, p = 0.029); worse PLWCI sleep impairment was associated with worse mastery (β = 0.104, p = 0.004). Poor PLWCI sleep quality was associated with lower caregiver mastery; the effect was larger for females than males. PLWCI being less sleepy during the day (β = 0.104, p = 0.055) and having worse sleep impairment (β =-0.163, p = 0.039) were both associated with more caregiver burden. There is a critical need to address the effects of PLWCI sleep disruption on caregivers in dementia care services.},
}

@article {pmid41576501,
year = {2026},
author = {Jayaswamy, PK and Ambrish, T and Sangamesh, VC and Kabekkodu, SP and Kellarai, A and Shetty, J and Shetty, P},
title = {EGFR-Annexin A2 signaling-mediated tauopathy in amyloid-β and aluminum chloride-induced Alzheimer's disease and its modulation by the HDAC inhibitor butyrate.},
journal = {Ecotoxicology and environmental safety},
volume = {310},
number = {},
pages = {119775},
doi = {10.1016/j.ecoenv.2026.119775},
pmid = {41576501},
issn = {1090-2414},
abstract = {Alzheimer's disease (AD) is typified by amyloid-β (Aβ) accumulation and tauopathy, culminating in synaptic destabilization, dendritic atrophy, and widespread neurodegeneration. Epidermal growth factor receptor (EGFR), prominently expressed during neurodevelopment, is largely quiescent in adulthood but undergoes pathological reactivation in AD, with its mechanistic contribution remaining elusive. Here, we delineate the EGFR-Annexin A2 (AnxA2) signaling nexus as a pivotal mediator of tau hyperphosphorylation in Aβ1-42-challenged SH-SY5Y and PC12 neuronal cultures and in aluminum chloride (AlCl3)/D-galactose (D-gal)-induced AD rat models. In vitro, Aβ1-42 orchestrated synergistic EGFR-AnxA2 activation, triggering site-specific tau phosphorylation (Thr231/Ser396), synaptic protein depletion, apoptotic cascades, neuroinflammatory signaling, and plasminogen activator inhibitor-1 (PAI-1)-driven fibrinolytic deficits. In vivo, AlCl3/D-gal rats displayed hippocampal EGFR-AnxA2 upregulation, region-specific tauopathy, cognitive impairments in Open Field and Novel Object Recognition paradigms, oxidative perturbations, and elevated TNF-α. Butyrate intervention abrogated EGFR-AnxA2 hyperactivity, attenuated tau pathology, restored PAI-1/tissue plasminogen activator homeostasis, and mitigated oxidative stress and neuroinflammation. Moreover, butyrate preserved synaptic and dendritic architecture, modulated apoptotic effectors by upregulating Bcl-2 and suppressing Bad, and enhanced neuronal viability. In vivo pre-and post-treatment paradigms improved behavioral and molecular outcomes, with prophylactic administration exhibiting superior efficacy. Collectively, these findings establish EGFR-AnxA2 as a central driver of tauopathy and identify prophylactic butyrate as a mechanistically grounded, diet-derived neuroprotective strategy capable of attenuating tau hyperphosphorylation, synaptic loss, and neuroinflammation in AD.},
}

@article {pmid41576475,
year = {2026},
author = {Besser, LM and Forrester, S and Mitsova, D and Maillard, P and DeCarli, C and Whitmer, R and Meyer, OL},
title = {Residential segregation of Black and Latinx older adults and brain imaging outcomes.},
journal = {Social science & medicine (1982)},
volume = {393},
number = {},
pages = {118995},
doi = {10.1016/j.socscimed.2026.118995},
pmid = {41576475},
issn = {1873-5347},
abstract = {Ethnoracial segregation has been associated with worse cognitive functioning among Black older adults, while its impact on Latinx individuals is less clear. We investigated whether Black and Latinx older adults living in segregated neighborhoods demonstrate worse magnetic resonance imaging (MRI) outcomes. We used data on participants from the University of California Davis Alzheimer's Disease Research Center. MRI outcomes included hippocampal and white matter hyperintensity (WMH) volumes. Black and Latinx segregation was defined using the Getis-Ord (Gi∗) statistic, which compares the proportion of Black or Latinx residents, respectively, in the participant's Census tract to surrounding neighborhoods and greater study region (higher Gi∗ = greater clustering/segregation). Multivariable linear regression analyses examined associations between Gi∗ segregation measures and MRI outcomes, stratified by the participants' ethnoracial group (Black, Latinx, or White). Participants (n = 269) were on average 74 ± 7 years of age and 24 % were Black, 25 % were Latinx, and 51 % were White. In adjusted analyses, Black participants in more Latinx segregated neighborhoods had lower hippocampal volumes, and Latinx participants in more Black segregated neighborhoods had lower hippocampal volumes. Latinx participants in more Latinx segregated neighborhoods had greater white matter hyperintensity volumes. Overall, Black and Latinx but not White participants living in segregated neighborhoods had worse MRI outcomes. Future studies are needed to replicate our findings in geographically diverse samples and to elucidate the potential psychosocial/social determinant and biological mechanisms that relate segregation to brain health (e.g., Latinx segregated neighborhoods may have fewer recreational and physical activity resources to promote healthy lifestyles).},
}

@article {pmid41576435,
year = {2026},
author = {Wang, L and Niu, J and Chen, X and Zhu, Y and Hou, X},
title = {Light-addressable sandwich photoelectrochemical immunosensor array and lateral flow immunoassays with self-calibration using quantum dots-sensitized and porphyrin-engineered MOFs for accurate detection of amyloid β-proteins.},
journal = {Biosensors & bioelectronics},
volume = {298},
number = {},
pages = {118424},
doi = {10.1016/j.bios.2026.118424},
pmid = {41576435},
issn = {1873-4235},
abstract = {Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the accumulation of amyloid-beta (Aβ) plaques, making Aβ a crucial biomarker for early diagnosis. In this study, we developed a novel light-addressable sandwich photoelectrochemical (PEC) immunosensor array for the detection of Aβ42, aiming to enhance diagnostic methods for AD. The array utilized cadmium telluride quantum dot-sensitized UiO-66 (U@C) as the sensing matrix and PCN-224@ZnIn2S4 nanoflower heterojunctions (P@Z) as immunoprobes, enabling multiplexed detection through laser pen activation on a single FTO electrode with a self-calibration method to minimize background noise and baseline drift. The assay required 60 min for incubation steps before detection; however, with 11 simultaneous detection points, it significantly reduced batch processing time and enhanced practicality. For point-of-care applications, we also developed a PEC-lateral flow immunoassay (PEC-LFIA) test strip that allowed for real-time, quantitative detection of Aβ42 with only 15 min of incubation required for testing. Both platforms effectively detected Aβ42 in PBS, artificial cerebrospinal fluid (CSF), and human plasma at concentrations ranging from fg/mL to ng/mL. Notably, sensitivity in human plasma was five times greater than that in artificial CSF. The PEC array achieved detection limits of 19.5 fg/mL in CSF and 3.1 fg/mL in plasma, while the PEC-LFIA strip demonstrated limits of 17.8 fg/mL in CSF and 3.1 fg/mL in human plasma. These advancements significantly reduced patient burden and brought us closer to utilizing a single drop of blood for monitoring brain aging.},
}

@article {pmid41576283,
year = {2026},
author = {Axell, E and Carlsson, A and Lindberg, M and Bernfur, K and Sparr, E and Linse, S},
title = {Solubility and Metastability of the Amyloidogenic Core of Tau.},
journal = {ACS chemical neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1021/acschemneuro.5c00784},
pmid = {41576283},
issn = {1948-7193},
abstract = {Intracellular deposits of neurofibrillary tau tangles and extracellular Aβ plaques are closely associated with Alzheimer's disease. The mapping of thermodynamic parameters, including solubility limits, indicates when a protein forms amyloid fibrils or remains in solution. This reveals the direction of change of the system and may help in understanding drift and steady states in living systems. Here we have developed methodology for tau solubility quantification and determined the solubility of the amyloidogenic core fragment of tau in vitro. We monitored the concentration of free tau304-380C322S fragment at 37 °C in phosphate buffer at pH 8.0 using three separate methods: HPLC-UV, derivatization with ortho-phthalaldehyde and scintillation counting. The measurements were repeated over time until a stable value was reached, implying that an equilibrium with fibrils had been established. The solubility measurements converged on a free monomer concentration of 6.1 ± 3.5 nM, which represents the solubility of the fragment under the current experimental conditions.},
}

@article {pmid41575766,
year = {2026},
author = {},
title = {Elecsys - a second blood test for Alzheimer's disease.},
journal = {The Medical letter on drugs and therapeutics},
volume = {68},
number = {1747},
pages = {18-20},
doi = {10.58347/tml.2026.1747b},
pmid = {41575766},
issn = {1523-2859},
}

@article {pmid41575675,
year = {2026},
author = {Kopalli, SR and Wankhede, N and Rahangdale, SR and Sammeta, S and Aglawe, M and Koppula, S and Taksande, B and Upaganlawar, A and Umekar, M and Kale, M},
title = {Age-driven dysbiosis: gut microbiota in the pathogenesis and treatment of aging disorders.},
journal = {Biogerontology},
volume = {27},
number = {1},
pages = {42},
pmid = {41575675},
issn = {1573-6768},
mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Dysbiosis/therapy/microbiology ; *Aging/physiology ; Animals ; Probiotics/therapeutic use ; },
abstract = {Aging, a complex physiological and molecular process, has undergone significant changes, of which gut microbiome composition has surfaced as an important key in the maintenance of neurological health. Recent studies have revealed the significant impact of age-related gut dysbiosis in the induction of neuroinflammation, metabolic syndrome, disruptions in gut-brain axis, and age-related neurological decline. Although significant studies have revealed the impact of the microbiome-gut-brain axis in individual neurological diseases, an aging-focused holistic synthesis has not yet been adequately developed. This review provides a critical assessment of the involvement of age-related dysbiosis of gut microbiota in the development and progression of neurological disorders such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, and cognitive aging of the elderly, and to focus on age-related microbial patterns and mechanisms of dysbiosis related to neurological aging, including inflammation and immune system dysregulation, metabolic changes, oxidative stress, barrier dysfunction, and gut-brain communication through enteroendocrine, enteric neural, and vagal mechanisms, and to emphasize disease-specific and common microbial patterns of dysbiosis and beneficial and harmful microbial roles in aging diseases. This review assesses some of the latest promising therapies aimed at the microbiota, such as probiotics, prebiotics, dietary therapies, fecal microbiota transplantation, as well as pharmacological therapies, and critically discusses their limitations in terms of interindividual variability and their generalisation and applicability. Focusing on mechanistic, comparative, and translation aspects, this review offers a comprehensive approach to neurological aging due to gut microbiota and identifies gaps for future precision microbiome-based interventions.},
}

Humans
*Gastrointestinal Microbiome/physiology
*Dysbiosis/therapy/microbiology
*Aging/physiology
Animals
Probiotics/therapeutic use

@article {pmid41575615,
year = {2026},
author = {Karur, P and Kaldas, M and Ramesh Babu, YS and Parmar, MS},
title = {Phosphorylated Tau Biomarkers in Alzheimer's Disease: From Early Detection to Clinical Potential-A Comprehensive Review.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {389},
pmid = {41575615},
issn = {1559-1182},
mesh = {*Alzheimer Disease/diagnosis/metabolism ; Humans ; *tau Proteins/metabolism ; *Biomarkers/metabolism/blood/cerebrospinal fluid ; Phosphorylation ; Early Diagnosis ; Animals ; },
abstract = {Alzheimer's disease (AD) is characterized by the pathological accumulation of neurofibrillary tangles (NFTs) and amyloid plaques, with hyperphosphorylated tau protein playing a central role in the formation of NFTs. Among the various phosphorylation sites on tau, p-tau181, p-tau231, and p-tau217 have emerged as promising biomarkers for AD. In addition, given the complexity of tau modifications across multiple sites, recent studies have explored tau forms phosphorylated at several sites simultaneously, hypothesizing that multi-site phosphorylation may offer greater diagnostic value than single-site modifications. These biomarkers can be measured in plasma and cerebrospinal fluid (CSF) using immunoassays, and their levels can be correlated with neuroimaging techniques like positron emission tomography (PET) and magnetic resonance imaging (MRI). This review article comprehensively compares these three phosphorylation sites to evaluate their roles as biomarkers in AD, focusing on their diagnostic accuracy, utility in early detection, and potential for monitoring disease progression. Each biomarker offers unique advantages and disadvantages, which influence its applicability in both clinical and research settings. Further, the review also highlights the evolving nature of this field, emphasizing the need for standardized approaches and further research to validate these biomarkers across diverse populations and integrate them into routine clinical practice. By synthesizing current evidence, including recent validation of fully automated platforms for plasma p-tau, this article provides insights into the transformative potential of tau biomarkers for improving AD diagnosis and management. The FDA's clearance of a plasma p-tau217-based blood test in May 2025 represents a pivotal step toward accessible, non-invasive AD diagnostics. This development highlights the valuable role of tau as a potential biomarker for the disease.},
}

*Alzheimer Disease/diagnosis/metabolism
Humans
*tau Proteins/metabolism
*Biomarkers/metabolism/blood/cerebrospinal fluid
Phosphorylation
Early Diagnosis
Animals

@article {pmid41575570,
year = {2026},
author = {Fertan, E and Kedia, S and Nolan, G and Meisl, G and Cotton, MW and Müller, KH and Zhang, Z and Muresan, L and Quaegebeur, A and Spillantini, MG and Klenerman, D},
title = {Early synaptic pathology is associated with small tau aggregates in Alzheimer's disease.},
journal = {Acta neuropathologica},
volume = {151},
number = {1},
pages = {7},
pmid = {41575570},
issn = {1432-0533},
mesh = {Humans ; *Alzheimer Disease/pathology/metabolism ; *tau Proteins/metabolism ; Female ; Male ; *Synapses/pathology/metabolism ; Aged ; Aged, 80 and over ; *Synaptosomes/pathology/metabolism ; *Protein Aggregation, Pathological/pathology/metabolism ; Middle Aged ; Brain/pathology/metabolism ; },
abstract = {Alzheimer's disease (AD) is phenotypically characterised by progressive memory loss, which has been linked to tau aggregation and synaptic dysfunction. Here we characterised the nanoscopic tau aggregates in individual synaptosomes from AD cases and controls, measuring their number and size using SynPull with direct stochastic optical reconstruction microscopy (dSTORM). A total of 7888 synaptosomes from pre-frontal cortex samples were studied, showing the presence of AT8-positive tau aggregates in a small fraction of synaptosomes (~ 3%) from control brains, reaching ~ 20% by Braak stage 6. These key findings of the intra-synaptic localisation of aggregates and existence of synaptic tau pathology at Braak stage 3-preceding tangle formation in this region, were confirmed using aggregate-specific single-molecule array (SIMOA) with proteinase K digestion, three-dimensional super-resolution microscopy, stimulated emission depletion microscopy (STED), and immunohistochemistry. The aggregates also grew in size with AD progression with an average length of 117 nm at stage 0, 154 nm at stage 3 and 182 nm at stage 6, however they mostly remained non-elongated (circular) with average eccentricity values remaining below 0.8. We then investigated the multi-phosphorylation of synaptic tau aggregates for AT8 and T181 and quantified their co-localisation with phosphatidylserine and CD47, synaptic "eat me" and "don't eat me" signals respectively, along with synaptogyrin-3, which contributes to tau-mediated synaptic dysfunction. T181, phosphatidylserine, and synaptogyrin-3 co-localisation with AT8-positive tau were higher during stage 3 and CD47 was lower, indicating early synaptic pathology is associated with the formation of small tau aggregates, contributing to microglia-driven synaptic loss.},
}

Humans
*Alzheimer Disease/pathology/metabolism
*tau Proteins/metabolism
Female
Male
*Synapses/pathology/metabolism
Aged
Aged, 80 and over
*Synaptosomes/pathology/metabolism
*Protein Aggregation, Pathological/pathology/metabolism
Middle Aged
Brain/pathology/metabolism

@article {pmid41575481,
year = {2026},
author = {Arora, G and Kumar, A and Silakari, P and Piplani, P},
title = {Design, synthesis and pharmacological evaluation of coumarin tethered 1,3,4-oxadiazole conjugates as dual binding site acetylcholinesterase ligands targeting Alzheimer's disease.},
journal = {Molecular diversity},
volume = {},
number = {},
pages = {},
pmid = {41575481},
issn = {1573-501X},
}

@article {pmid41575410,
year = {2026},
author = {Neth, BJ and Graff-Radford, J and Cogswell, PM and Johnson, DR and Botha, H and McCarter, SJ and Jones, DT and Conkins, MM and Hardin, DB and Spence, JJ and Rhegness, CL and Allen, LA and Coburn, RP and Pounders, JD and Burkett, BJ and Pillai, JJ and Day, GS and Graff-Radford, NR and Lachner, C and Messina, SA and Jain, MK and Stricker, NH and Machulda, MM and Fields, JA and Boots, EA and Aduen, PA and Barnard, LR and Remold, MA and Anderlik, AM and Asleson, KM and Martin, LL and Klaassen, JA and Larsen, JJ and Algeciras-Schimnich, A and Bornhorst, JA and Rumilla, AM and Jack, CR and Boeve, BF and Knopman, DS and Petersen, RC and Ramanan, VK},
title = {Establishing an Alzheimer Disease Therapeutics Clinic: Experience From a Year of Evaluations.},
journal = {Mayo Clinic proceedings},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.mayocp.2025.09.019},
pmid = {41575410},
issn = {1942-5546},
abstract = {OBJECTIVE: To describe the establishment and initial experience of a multidisciplinary Alzheimer disease treatment clinic (ADTC), focusing on the evaluation of eligibility for novel disease-modifying therapies, as well as the treatment and monitoring of qualifying patients.

PATIENTS AND METHODS: We completed a retrospective review of cases seen through the Mayo Clinic ADTC between October 2, 2023, and December 31, 2024. Typical evaluations occurred over 4 to 5 days and included multimodal testing, office visits, and a weekly case conference modeled on tumor board meetings.

RESULTS: Patients evaluated in the ADTC (N=232) ranged from 52 to 85 years of age (mean age, 71.2 years). Most patients had mild cognitive impairment (128 of 232 [55%]) or mild dementia (72 of 232 [31%]) syndromes. Overall, 121 patients (52%) were judged eligible for antiamyloid therapy. Eligibility rates were higher among internal (from our institution) referrals compared with external referrals (63% [146 of 232] vs 37% [86 of 232). Reasons for treatment ineligibility were typically multiple but commonly included magnetic resonance imaging features, too severe cognitive/functional impairment, and general health conditions believed likely to increase therapeutic risks. In some cases, the ADTC evaluation uniquely identified treatment risk factors, such as cerebral amyloid angiopathy, that had not been previously discussed with patients. Through shared decision making, approximately 30% of eligible patients (25 of 81) ultimately deferred antiamyloid therapy. In addition, approximately 10% of patients evaluated in the ADTC were amyloid-negative by positron emission tomography, suggesting non-Alzheimer disease diagnoses for their presentations.

CONCLUSION: The ADTC facilitated systematic implementation of antiamyloid therapies for early Alzheimer disease and provided a scalable foundation for integrating future approved treatment options.},
}

@article {pmid41575328,
year = {2026},
author = {Bhadane, P and Khairnar, A and Pandya, K and Naha, A and Kumar, D and Abutwaibe, KA and Desai, J and Bombatkar, N and Rajput, P and Kumar, D},
title = {Targeted Delivery of Quercetin to the Brain via a Modified Polymeric Nanocarrier.},
journal = {Macromolecular bioscience},
volume = {26},
number = {1},
pages = {e00503},
doi = {10.1002/mabi.202500503},
pmid = {41575328},
issn = {1616-5195},
support = {RGSTC/File-2025/DPP-355/CR-27/160//Rajiv Gandhi Science and Technology Commission, Government of Maharashtra/ ; },
mesh = {*Quercetin/pharmacology/chemistry/pharmacokinetics ; Animals ; *Brain/metabolism/drug effects ; *Nanoparticles/chemistry ; Polyethylene Glycols/chemistry ; *Drug Carriers/chemistry/pharmacology ; Polyethyleneimine/chemistry ; Humans ; Rats ; *Drug Delivery Systems ; Particle Size ; },
abstract = {Quercetin (Qt) exhibits significant neuroprotective potential in Alzheimer's disease; however, its clinical translation is limited by poor solubility, low permeability, and inadequate brain bioavailability. In this study, a modified polymeric nanocarrier was developed to enhance Qt delivery to the brain. Polyethyleneimine (PEI) was conjugated with polyethylene glycol (PEG) and further functionalized with phenylalanine to reduce PEI-associated toxicity and improve brain-targeting efficiency. Successful polymer synthesis was confirmed by FT-IR spectroscopy, showing characteristic S─S bond formation at 790 cm[-] [1], mass spectrometry (m/z 1087.3), and differential scanning calorimetry. Nanoparticles were optimized using a Quality by Design approach, yielding an experimental particle size of 161.4 ± 1.10 nm, zeta potential of 15.9 ± 2.5 mV, and high entrapment efficiencies of 84.21 % and 86.74 % for Qt-PEI-Np and Qt-PEI-PEG-S-S-AA-Np, respectively. SEM analysis revealed spherical nanoparticles with nanoscale surface roughness and good stability. In vitro release studies demonstrated sustained Qt release (98 % over 48 h). MTT assays and cytokine analysis (TNF-α, IL-1β, IL-6) confirmed biocompatibility. Enhanced intestinal permeability, absence of hippocampal toxicity, and effective BBB transport further support the potential of this nanocarrier for targeted neurotherapeutic delivery.},
}

*Quercetin/pharmacology/chemistry/pharmacokinetics
Animals
*Brain/metabolism/drug effects
*Nanoparticles/chemistry
Polyethylene Glycols/chemistry
*Drug Carriers/chemistry/pharmacology
Polyethyleneimine/chemistry
Humans
Rats
*Drug Delivery Systems
Particle Size

@article {pmid41575052,
year = {2026},
author = {Brown, SE and Bowen, ZJ and Rosati Yoos, LL and Sakthi-Velavan, S},
title = {A Unique Case of Post-Subarachnoid Hemorrhage Cerebral Atrophy and Its Implications on Alzheimer's Disease.},
journal = {American journal of Alzheimer's disease and other dementias},
volume = {41},
number = {},
pages = {15333175261420559},
doi = {10.1177/15333175261420559},
pmid = {41575052},
issn = {1938-2731},
mesh = {Humans ; Female ; Aged, 80 and over ; *Subarachnoid Hemorrhage/complications/pathology ; *Alzheimer Disease/pathology/etiology ; Atrophy/pathology/etiology ; Gliosis/pathology ; *Frontal Lobe/pathology ; Cadaver ; },
abstract = {Subarachnoid hemorrhage (SAH) has been reported to cause glial scarring within a short timeframe. Due to the high mortality rate of SAH, there is limited research on its long-term effects and relation to neurodegenerative disorders. This report aims to investigate a combination of healed SAH and Alzheimer's Disease (AD) pathology. A 90-year-old female cadaver, in the anatomy laboratory, was found to have an irregular surgical scar in the right frontoparietal bone. Upon dissection, the right frontal lobe was discovered to be atrophic with a concavity. Histopathology exhibited significant gliosis and corpora amylacea (CA). The cause of death was AD, and past medical history revealed an aneurysmal SAH during childbirth 60 years ago. CA and gliosis are common findings in aging, ischemia, and AD. These findings contribute to the knowledge of the long-term effects of SAH and necessitate further research on the pathogenesis of AD in relation to cerebral ischemia.},
}

Humans
Female
Aged, 80 and over
*Subarachnoid Hemorrhage/complications/pathology
*Alzheimer Disease/pathology/etiology
Atrophy/pathology/etiology
Gliosis/pathology
*Frontal Lobe/pathology
Cadaver

@article {pmid41574967,
year = {2026},
author = {Nôga, DA and Meth, EMS and Almajni, A and Rossi, V and Zetterlund, C and Noory, SFM and Danek, M and Al-Grety, A and Pacheco, AP and Wu, M and Phillipson, M and Zetterberg, H and Kultima, K and Xue, P and Benedict, C},
title = {Increased p-Tau181 Levels After Overnight Wakefulness Are Associated With Neuroticism in Young Women.},
journal = {Journal of sleep research},
volume = {},
number = {},
pages = {e70278},
doi = {10.1111/jsr.70278},
pmid = {41574967},
issn = {1365-2869},
support = {NNF23OC0081873//Novo Nordisk Fonden/ ; M24-0251//Åke Wiberg Stiftelse/ ; FO2023-0292//Hjärnfonden/ ; 2023-00356//Vetenskapsrådet/ ; 2022-01018//Vetenskapsrådet/ ; 2019-02397//Vetenskapsrådet/ ; //Pharmaceutical Biosciences at Uppsala University, Sweden/ ; 101053962//European Union's Horizon Europe research/ ; #ALFGBG-71320//Swedish State Support for Clinical Research/ ; #201809-2016862//Alzheimer Drug Discovery Foundation (ADDF), USA/ ; #ADSF-21-831376-C, #ADSF-21-831381-C, #ADSF-21-831377-C and #ADSF-24-1284328-C//AD Strategic Fund and the Alzheimer's Association/ ; //European Partnership on Metrology/ ; NEuroBioStand, #22HLT07//European Union's Horizon Europe Research and Innovation Programme/ ; //Bluefield Project/ ; //Cure Alzheimer's Fund/ ; //Olav Thon Foundation, the Erling-Persson Family Foundation/ ; //Familjen Rönströms Stiftelse/ ; //Familjen Beiglers Stiftelse/ ; //Stiftelsen för Gamla Tjänarinnor/ ; 860197//Marie Skłodowska-Curie grant/ ; JPND2021-00694//European Union Joint Programme-Neurodegenerative Disease Research/ ; //National Institute for Health and Care Research/ ; //University College London Hospitals Biomedical Research Centre/ ; UKDRI-1003//UK Dementia Research Institute/ ; },
abstract = {Night shift work can impair attention and increase biomarkers linked to neurodegenerative processes. Understanding factors that influence resilience to, or vulnerability under, sleep loss is therefore essential for identifying groups at particular risk. In this within-subjects study, we examined two potential modulators of vulnerability in 54 healthy, naturally cycling women aged 21-33 years: the ovarian hormone estradiol, known for its neuroprotective properties and the personality trait neuroticism, previously associated with stress sensitivity. Participants completed one night of habitual sleep followed by one night of overnight wakefulness, mimicking a transition from an off- to an on-night shift. Women with higher morning blood estradiol levels or lower neuroticism (indexed by higher emotional stability scores) exhibited non-significant tendencies towards faster reaction times during successful psychomotor vigilance test (PVT) trials, which assess sustained attention. Notably, lower neuroticism was also associated with significantly fewer attentional lapses (reaction times ≥ 500 ms) during the PVT, whereas estradiol levels were not. However, neither trait modulated the overall decline in attentional performance observed following the night-shift condition. In contrast, higher neuroticism-but not estradiol-predicted elevated morning levels of phosphorylated tau at threonine 181 (p-Tau181), a plasma biomarker associated with Alzheimer's disease-related neurodegenerative processes, after the night shift condition. These findings highlight neuroticism as a psychological factor linked to increased neurobiological sensitivity to overnight wakefulness among women.},
}

@article {pmid41574926,
year = {2026},
author = {Eckert, A and Georgescu, D and Seifritz, E and Müller, WE},
title = {Improvement of age-related neurocognitive disorders by Ginkgo biloba extract: neuroprotection in focus.},
journal = {International journal of psychiatry in clinical practice},
volume = {},
number = {},
pages = {1-14},
doi = {10.1080/13651501.2026.2617217},
pmid = {41574926},
issn = {1471-1788},
abstract = {Oxidative stress and enhanced free radical production with subsequent mitochondrial dysfunction and neurodegeneration are major pathomechanisms for the ageing spectrum of neurocognitive disorders ranging from subjective cognitive decline over mild cognitive impairment to Alzheimer's disease (AD) and vascular mild cognitive impairment (MCI) and vascular dementia (VD). Due to its radical scavenging, antioxidative and mitochondrial function-improving properties standardised Ginkgo biloba extracts (GBE) target several key processes of neurodegeneration. These include mitochondrial dysfunction, impaired mitochondrial quality control, and reduced energy metabolism. GBE's benefits also include supporting neuroplasticity, the brain's ability to form new neural connections, and reducing neuroinflammation, a major driver of disease progression in neurodegenerative conditions. As a consequence, GBE improves several aspects of cognitive dysfunction within the broad spectrum of neurocognitive disorders as indicated by a large body of evidence from randomised controlled studies.},
}

@article {pmid41574776,
year = {2026},
author = {Kandimalla, M and Lim, S and Jacobson, DN and Lee, J and Min, PH and Nycklemoe, ME and Lee, SB and Lundt, ES and Botha, H and Graff-Radford, J and Jones, DT and Cogswell, PM and Vemuri, P and Kantarci, K and Knopman, DS and Jack, CR and Petersen, RC and Lowe, VJ},
title = {Neuroinflammation demonstrated by [11]C-ER176 PET with amyloid and tau pathology.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {1},
pages = {e71027},
doi = {10.1002/alz.71027},
pmid = {41574776},
issn = {1552-5279},
support = {R01 AG073282/AG/NIA NIH HHS/United States ; P30 AG62677//Alzheimer's Drug Discovery Foundation/ ; R01 AG068206/AG/NIA NIH HHS/United States ; U01 AG006786/AG/NIA NIH HHS/United States ; P50 AG016574/AG/NIA NIH HHS/United States ; R01 AG034676/AG/NIA NIH HHS/United States ; R37 AG011378/AG/NIA NIH HHS/United States ; R01 AG041851/AG/NIA NIH HHS/United States ; U19 AG063911/AG/NIA NIH HHS/United States ; R01 NS097495/NS/NINDS NIH HHS/United States ; R01 AG056366/AG/NIA NIH HHS/United States ; U01 NS100620/NS/NINDS NIH HHS/United States ; //the GHR Foundation/ ; //the Elsie and Marvin Dekelboum Family Foundation/ ; //the Alexander Family Alzheimer's Disease Research Professorship of the Mayo Clinic/ ; //the Liston Award Family Foundation/ ; //the Robert H. and Clarice Smith and Abigail van Buren Alzheimer's Disease Research Program, the Schuler Foundation/ ; //the Mayo Foundation for Medical Education and Research/ ; HY-202400000003953//Research Fund of Hanyang University/ ; //Bio&Medical Technology Development Program of the National Research Foundation/ ; RS-2023-00226494//Korean government (MSIT)/ ; },
mesh = {Humans ; *Positron-Emission Tomography ; Male ; *tau Proteins/metabolism ; Female ; *Alzheimer Disease/diagnostic imaging/metabolism/pathology ; Aged ; Receptors, GABA/metabolism ; *Cognitive Dysfunction/diagnostic imaging/metabolism/pathology ; *Neuroinflammatory Diseases/diagnostic imaging/metabolism ; Microglia/metabolism ; *Brain/metabolism/diagnostic imaging/pathology ; *Amyloid/metabolism ; Aged, 80 and over ; Inflammation/diagnostic imaging/metabolism ; Carbon Radioisotopes ; },
abstract = {INTRODUCTION: Understanding neuroinflammation across the Alzheimer's disease (AD) spectrum is essential to elucidate disease mechanisms and individualize therapy.

METHODS: Human microglial translocator protein (TSPO) expression under inflammatory stimuli was assessed by immunoblot experiments. Ninety-six participants were enrolled across four groups: cognitively unimpaired amyloid (CU A) + and -, mild cognitive impaired (MCI) A+, and Alzheimer's disease dementia (ADD) A+. Neuroinflammation using [11]C-ER176 TSPO positron emission tomography (PET) was compared to amyloid and tau PET. Correlations between neuroinflammation, amyloid, and tau pathology were examined across disease stages.

RESULTS: TSPO was upregulated in human microglia under AD-like inflammatory conditions. Neuroinflammation, defined by PET TSPO, increased in CU A+ participants and became more widespread with increasing disease severity, aligning with worsening amyloid and tau pathology. Associations with tau were particularly extensive in temporal and parietal regions.

DISCUSSION: These findings suggest probable amyloid association with early microglial activation, while tau pathology is closely tied to wider distribution of neuroinflammation.

HIGHLIGHTS: TSPO expression increases in human microglia under AD-like inflammation. [11]C-ER176 PET shows stage-dependent neuroinflammation across the AD spectrum. Neuroinflammation overlaps with tau and is more widespread in amyloid-positive individuals. Activity peaks in MCI, stabilizes later, and relates to vascular and neurodegenerative changes.},
}

Humans
*Positron-Emission Tomography
Male
*tau Proteins/metabolism
Female
*Alzheimer Disease/diagnostic imaging/metabolism/pathology
Aged
Receptors, GABA/metabolism
*Cognitive Dysfunction/diagnostic imaging/metabolism/pathology
*Neuroinflammatory Diseases/diagnostic imaging/metabolism
Microglia/metabolism
*Brain/metabolism/diagnostic imaging/pathology
*Amyloid/metabolism
Aged, 80 and over
Inflammation/diagnostic imaging/metabolism
Carbon Radioisotopes

@article {pmid41574617,
year = {2026},
author = {Sharma, P and Goyal, R},
title = {Mitigation of Circadian Disruption-Induced Amyloid Pathology, Neuroinflammation, and Cognitive Disability in C57BL/6J Mice Using Estradiol.},
journal = {ACS chemical neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1021/acschemneuro.5c00650},
pmid = {41574617},
issn = {1948-7193},
abstract = {Circadian rhythms (CRs) are intrinsic 24 h cycles that regulate critical physiological processes, including sleep-wake behavior, hormonal signaling, and cognition. Disruption of CRs, often caused by chronic aberrant light exposure, has been linked to neurodegenerative diseases such as Alzheimer's disease (AD), through altered expression of core clock genes and neurotransmitter imbalances. Estrogen is a known neuromodulator that influences both circadian timing and cognitive function, yet the mechanistic interplay between estrogen and circadian dysregulation in neurodegeneration remains underexplored. In this study, we investigated whether estradiol could mitigate neuropathological and circadian disturbances induced by chronic, constant light (LL) exposure in female C57BL/6J mice. Mice were exposed to LL for 6 or 10 weeks (LL6, LL10) to model progressive CR disruption. LL10 significantly delayed locomotor rhythms (p < 0.0001), elevated hippocampal amyloid-β (Aβ) levels (p = 0.0018), and reduced SCN GABA and glutamate levels (p < 0.01), compared to LL6 and light-dark (LD) controls. Both LL6 and LL10 also showed decreased hippocampal nitric oxide and glutathione levels (p < 0.05), indicating oxidative stress. Estradiol treatment (1.5 or 3 μg/kg) restored activity rhythms, reduced Aβ accumulation (p = 0.0019), and normalized SCN neurotransmitter levels (GABA; p = 0.0046; glutamate: p = 0.0003). These effects were abrogated by tamoxifen, suggesting estrogen receptor-mediated signaling. Histological analysis further showed that estradiol attenuated hippocampal inflammation and neuronal damage in LL10-exposed animals. These results demonstrate that estrogen protects against circadian disruption-induced neuropathology and supports its potential as a therapeutic agent in mitigating cognitive decline via ER-dependent pathways.},
}

@article {pmid41574602,
year = {2026},
author = {Feng, BD and Qin, JY and Qin, QQ and Xu, ZC and Zhang, HQ},
title = {GPR3 in neuro-metabolic-immune-reproductive nexus - a potential therapeutic target for Multi-System diseases.},
journal = {Annals of medicine},
volume = {58},
number = {1},
pages = {2619216},
doi = {10.1080/07853890.2026.2619216},
pmid = {41574602},
issn = {1365-2060},
mesh = {Humans ; *Receptors, G-Protein-Coupled/metabolism ; Signal Transduction ; *Neurodegenerative Diseases/metabolism/drug therapy ; Animals ; Reproduction/physiology ; Energy Metabolism ; Alzheimer Disease ; },
abstract = {BACKGROUND: GPR3(G-protein-coupled receptor 3), an orphan G-protein-coupled receptor (GPCR) with constitutive Gs activity, is expressed in the brain, liver, ovary, and other tissues, regulating cell proliferation, differentiation, and apoptosis across the nervous, reproductive, immune, and metabolic systems. This review synthesizes evidence on its integrated signaling and physiological functions to address the lack of a comprehensive multisystem pathophysiology overview.

METHODS: A systematic literature search was conducted on PubMed and Web of Science, using keywords such as "GPR3", "GPCR", "neurodegeneration", "metabolism", "immune", "reproduction", "agonist", "inhibitor", and "therapeutic target". This search identified GPR3's roles in neurodegenerative diseases, immune inflammation, reproduction, and energy metabolism. The analysis focused on signaling pathways, ligand regulation, and therapeutic potential.

RESULTS: The research indicates that GPR3 is involved in neuronal survival, synaptic plasticity, and microglial activity via the cAMP/PKA, PI3K/Akt, and β - arrestin pathways. It promotes amyloid - β formation in Alzheimer's disease (AD), yet provides neuroprotection in Parkinson's disease (PD) models. It may contribute to anxiety/depression - like states, maintain oocyte meiotic arrest in the ovary, and activate thermogenic genes in adipose tissue. GPR3 modulates immune responses. Using oleic acid (OA) and diphenyleneiodonium (DPI) as activators, and AF64394 and cannabidiol (CBD) as antagonists, it shows potential in disease models.

CONCLUSION: GPR3 acts as a central molecular hub integrating neural, metabolic, immune, and reproductive signaling, highlighting its potential as a therapeutic target for chronic multisystem disorders. However, its dual roles in certain pathologies and translation challenges necessitate further research.},
}

Humans
*Receptors, G-Protein-Coupled/metabolism
Signal Transduction
*Neurodegenerative Diseases/metabolism/drug therapy
Animals
Reproduction/physiology
Energy Metabolism
Alzheimer Disease

@article {pmid41574572,
year = {2026},
author = {O'Donnell, MG and Smith, T and Huang, Y and Baker, ZG},
title = {A Scoping Review of Dementia Research Using ALZConnected Forum Data.},
journal = {Western journal of nursing research},
volume = {},
number = {},
pages = {1939459251413009},
doi = {10.1177/01939459251413009},
pmid = {41574572},
issn = {1552-8456},
abstract = {BACKGROUND: Dementia is a rapidly growing global health challenge, affecting an estimated 57 million people worldwide and placing escalating demands on individuals living with the condition and those who care for them. As needs rise, many turn to digital platforms like ALZConnected, a moderated online forum offering space for sharing, support, and connection. While its use in research is expanding, to our knowledge, no scoping review has yet examined how ALZConnected has been leveraged as a data source in dementia-related studies.

OBJECTIVE: This scoping review aimed to identify and describe published studies that used the ALZConnected forum data to explore caregiver and persons living with dementia experiences, research approaches applied, and areas of focus.

METHOD: A systematic search of peer-reviewed journal articles, dissertations, and preprints published between 2011 and 2025 was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews reporting guidelines. Eligible studies analyzed ALZConnected content, centered on dementia caregivers or persons living with dementia, and reported original research. A total of 163 records were screened, with 28 studies included.

RESULTS: Studies applied qualitative and computational methods to explore caregiver emotional well-being, information-seeking, systemic challenges, peer support dynamics, and technological applications. ALZConnected was also used to model sentiment, develop algorithms, and analyze caregiver communication. A smaller number of studies examined posts authored by people living with dementia.

CONCLUSIONS: ALZConnected provides a rich, naturalistic data source for exploring dementia care discussions. Findings highlight its value for nursing research, intervention development, and care planning, particularly in under-resourced settings.},
}

@article {pmid41574438,
year = {2026},
author = {Cheng, ST and Lam, LCW},
title = {Do positive aspects of caregiving lessen burden and depression, or the other way round? A mixed-methods study.},
journal = {Aging & mental health},
volume = {},
number = {},
pages = {1-13},
doi = {10.1080/13607863.2026.2614952},
pmid = {41574438},
issn = {1364-6915},
abstract = {OBJECTIVES: Positive aspects of caregiving (PAC) are assumed to protect against caregiver suffering, but evidence is lacking. Two studies examined this assumption through testing the reciprocal causality between PAC and burden/depression, and exploring the mechanisms linking these constructs.

METHODS: MethodsIn Study One, 99 dementia caregivers were interviewed six months apart. In Study Two, 45 caregivers provided 620 diaries across eight weeks.

RESULTS: In Study One, baseline burden predicted increased depressive symptoms, whereas baseline depressive symptoms predicted less PAC. Although burden was unrelated to PAC concurrently, burden was found to strengthen PAC after depression was controlled for (statistical suppression). Contrary to prevailing assumption, PAC predicted neither burden nor depression. In Study Two, 213 of the 620 diaries contained narratives linking burden to PAC. Supporting the PAC-enhancing role of burden, four mechanisms were extracted using thematic analysis, describing unrelenting caregiving stress enriching the significance of their work and pressuring them to learn, to push beyond boundaries, and to transform thinking.

CONCLUSION: Chronic hardship may be a breeding ground for positive meanings, yet also increasing depression, undermining positivity. Consequently, burden has a direct positive effect, but an indirect negative effect via depression, on PAC. A conceptual model depicting such complex dynamics is proposed.},
}

@article {pmid41574278,
year = {2026},
author = {Hagan, B and Buss, SS and Fried, PJ and Shafi, MM and Turk, KW and Xie, KY and Frank, B and Passera, B and Ozdemir, RA and Budson, AE},
title = {Evaluating Alzheimer's disease with the TMS-EEG perturbation complexity index.},
journal = {Neuroscience of consciousness},
volume = {2026},
number = {1},
pages = {niaf062},
pmid = {41574278},
issn = {2057-2107},
abstract = {The Perturbation Complexity Index-State Transitions (PCI[ST]) measures the complexity of the brain's response to transcranial magnetic stimulation (TMS) using electroencephalography (EEG) and is sensitive to consciousness, such as minimally conscious states. Individuals with early-stage Alzheimer's disease (AD) show dysfunction of conscious processes, such as attention, working memory, episodic memory, and executive function, with relatively spared unconscious processes, such as procedural memory, operant conditioning, and priming. We sought to test the hypothesis that PCI[ST] would be reduced in AD compared to healthy aging. We assessed 28 participants with AD and 27 healthy controls (HC), measuring cognition with the Montreal Cognitive Assessment (MoCA) and disease severity with the Clinical Dementia Rating scale-Global (CDR-Global) and Sum of Boxes (CDR-SB). Results indicated lower PCI[ST] in the AD group (M = 20.1) compared to controls (M = 28.2) across both the motor cortex (M1) and inferior parietal lobule (IPL) TMS stimulation sites, suggesting that PCI[ST] may reflect the impaired conscious cognitive processes and functional capacity seen in AD. We therefore speculate that cortical dementias involve alterations in cortical complexity that may relate to deterioration of their conscious processes. This research opens the avenue for future studies in individuals with cortical dementia to examine the relationship between conscious processes, global measures of consciousness, and their underlying neuroanatomical correlates, in addition to enhancing our understanding of dementia and suggesting possible therapeutic strategies.},
}

@article {pmid41574214,
year = {2026},
author = {Patel, S and Prajapati, C and Rai, SN and Singh, SK},
title = {Bridging pathway dysfunction and therapy: novel compounds for neuroprotection.},
journal = {3 Biotech},
volume = {16},
number = {2},
pages = {79},
pmid = {41574214},
issn = {2190-572X},
abstract = {Recent finding in the field of neurodegenerative disease shows that dysregulation of signaling pathways like PI3K/AKT/mTOR, MAPK/ERK, NF-κB, Wnt/β-Catenin and apoptotic regulator, mitochondrial dysfunction, play pivotal role in the progression of Alzheimer, Parkinson, and other disease. Recent research indicates that disruptions in these interrelated pathways lead to oxidative harm, mitochondrial malfunction, aberrant protein aggregates, synaptic dysfunction, and eventually neuronal death. Numerous naturally occurring bioactive substances, like as genistein, curcumin, luteolin, and others, show great promise in combating these degenerative processes. These compounds improve neuronal survival as well as functional outcomes in laboratory experiments by modulating several signaling targets, restoring PI3K-Akt-mTOR, MAPK-ERK, Wnt/β-catenin, and NF-κB activity, restoring mitochondrial bioenergetics, limiting apoptosis, and reducing amyloid- β, α-synuclein accumulation. Numerous natural compounds with well-defined mechanisms of the actions and multitargeted therapeutic benefits are highlighted by a comprehensive evaluation of the available data, providing reliable and more affordable substitutes for one- target synthetic medicines. Despite its potential, issues including low bioavailability and low translational success persist. Overall, the results highlight the potential of understudied phytochemicals for creating more robust therapies against the development of neurodegenerative diseases and uncover important signaling centers that can be regulated by natural substances.},
}

@article {pmid41574151,
year = {2026},
author = {Georgiou, E and Comber, R and Alemam, M and Crosby, L and Kirwan, A and Smyth, F and Greene, E},
title = {Cognitive Impairment in Sjögren's Disease: Unmasking Alzheimer's Through CSF Biomarkers. A Case Report.},
journal = {Clinical case reports},
volume = {14},
number = {1},
pages = {e71909},
pmid = {41574151},
issn = {2050-0904},
abstract = {Cognitive impairment in Sjögren's disease (SD) is typically attributed to autoimmune mechanisms or small vessel disease. However, its overlap with neurodegenerative pathology remains poorly understood. We report a 74-year-old woman with clinically diagnosed SD presenting with progressive memory decline. She demonstrated severe amnestic deficits on neuropsychological testing and had a cerebrospinal fluid (CSF) profile consistent with Alzheimer's disease (AD), including low Aβ1-42 and elevated total tau and phosphorylated tau. MRI revealed only mild small vessel disease. This case highlights the diagnostic importance of CSF biomarkers in distinguishing neurodegenerative from autoimmune cognitive syndromes. Though the overlap may be coincidental, it raises the question of whether systemic inflammation in SD could contribute to AD pathogenesis. This case illustrates how neurodegenerative disease may be overlooked in patients with autoimmune conditions. In individuals with SD and persistent amnestic symptoms, biomarker testing can help distinguish Alzheimer's pathology from autoimmune cognitive syndromes and guide more accurate diagnosis and care.},
}

@article {pmid41573947,
year = {2025},
author = {Pusuluri, K and Arcasoy, AB and Iraji, A and Calhoun, VD},
title = {Diminished spatial dynamics and maladaptive spatial complexity link resting brain network disruption to cognition in schizophrenia.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2025.12.07.692856},
pmid = {41573947},
issn = {2692-8205},
abstract = {Resting-state fMRI studies increasingly emphasize the dynamic nature of brain networks. While most approaches examine temporal fluctuations in connectivity, we focus on the spatial dynamics and complexity at voxel level - how networks expand and contract, and change their structural complexity over time. Using dynamic independent component analysis (ICA), we investigate the hierarchical structure of the resulting time-varying spatial networks, from their broad periphery to their most active core. We combine this with fractal dimension (FrD) as a measure of a network's spatial complexity and analyze temporal changes (dynamic flexibility) in a network and synchronized fluctuations between network pairs (fractal dimension coupling, FrDC). We refer to this approach as "dynamic spatial network complexity and connectivity (dSNCC)". Using a combined cohort of 508 subjects (315 healthy controls, 193 schizophrenia patients), we found that schizophrenia is associated with higher mean FrD in several networks, suggesting more irregular patterns/boundaries and a disorganized network structure. Critically, patients showed significantly reduced dynamic flexibility, indicating their networks are "stuck" in a less adaptable state. This robust finding is evidenced by a synergistic loss of temporal standard deviations in both network volume and FrD across multiple networks and activity thresholds. This maladaptive complexity was associated with cognitive impairment, with several dSNCC measures showing significant associations with subject scores for processing speed, visual learning, and verbal learning. Higher complexity in these networks and more significantly, their reduced dynamic flexibility as seen in patients, were particularly associated with impaired performance. Furthermore, we found aberrant connectivity (FrDC) in schizophrenia, with certain network pairs exhibiting overly synchronized complexity changes. Our results demonstrate that dSNCC is a powerful tool for characterizing network dynamics and may potentially provide a measurable mechanism for maladaptation in schizophrenia, where the brain's inability to fluidly change its complexity may contribute to cognitive deficits and symptoms like disorganized thought. These findings highlight the importance of studying the intrinsic spatial dynamic properties to reveal the fundamental principles of brain network organization in health and disease. Our work represents a significant leap in complex systems neuroscience and provides a novel, quantifiable biomarker framework highly relevant for understanding and targeting other complex disorders characterized by network dysfunction, such as Alzheimer's disease, autism, or other mental health conditions.},
}

@article {pmid41573926,
year = {2025},
author = {Yang, X and Li, Y and Yao, M and Bibic, A and Duan, W and Lu, H and Wei, Z},
title = {Vascular smooth muscle cell loss, but not neuroinflammation, drives cerebrovascular reactivity impairment in Alzheimer's disease.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2025.12.01.691642},
pmid = {41573926},
issn = {2692-8205},
abstract = {INTRODUCTION: Cerebrovascular reactivity (CVR) impairment is a key feature of Alzheimer's disease (AD), but its mechanistic basis remains unclear. This study examined whether vascular smooth muscle cell (VSMC) loss, rather than amyloidosis or neuroinflammation, underlies CVR deficits.

METHODS: Non-contrast MRI, including phase-contrast and pseudo-continuous arterial spin labeling, was performed in mouse models of amyloidosis (5xFAD), VSMC degeneration (CADASIL), and lipopolysaccharide-induced neuroinflammation. Characterization of vascular, amyloid-β, and inflammatory markers were performed for pathological assessment.

RESULTS: CVR impairment emerged only when VSMC loss was present in CADASIL mice and at older ages in 5xFAD mice (9-12 months). Amyloid-β deposition occurred earlier than VSMC loss or CVR decline. Neuroinflammation primarily altered baseline cerebral blood flow without affecting CVR or VSMC integrity.

DISCUSSION: These findings identify VSMC degeneration as an important driver of CVR impairment independent of cerebral amyloid angiopathy or inflammation, highlighting vascular integrity as a potential therapeutic target in AD.

HIGHLIGHTS: Cerebrovascular reactivity (CVR) impairment occurred in 5xFAD mice only when vascular smooth muscle cell (VSMC) loss was present5xFAD mice exhibited prominent parenchymal but minimal vascular amyloid-β depositionVSMC developmental deficiency resulted in CVR impairment in a small-vessel disease (SVD) modelNeuroinflammation primarily altered baseline cerebral blood flow (CBF) without affecting CVR.},
}

@article {pmid41573824,
year = {2025},
author = {Wearn, A and Onuska, KM and Shanks, HRC and Gaurav, R and Lehéricy, S and Baracchini, G and Hughes, C and Tremblay-Mercier, J and Narayanan, S and Breitner, J and Poirier, J and Schmitz, TW and Turner, GR and Spreng, RN and , },
title = {Locus coeruleus degeneration is associated with cortical tau deposition and cognitive decline in older adults at familial risk of Alzheimer's disease.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2025.12.02.691923},
pmid = {41573824},
issn = {2692-8205},
abstract = {INTRODUCTION: The locus coeruleus (LC) is among the first sites of tau pathology in Alzheimer's disease (AD) and may seed neocortical tau.

METHODS: We used longitudinal neuromelanin-sensitive MRI to assess LC integrity in vivo in a cohort of cognitively unimpaired older adults with familial risk of AD in relation to tau and amyloid PET and long-term cognitive trajectories.

RESULTS: We showed that both LC integrity at baseline and its rate of degeneration over time independently predicted a neocortical pattern of tau deposition. In keeping with the known function of the LC, neuropsychological tests showed that LC integrity at baseline predicted changes in attention. Finally, we found that longitudinal LC degeneration correlated with memory decline in people with elevated neocortical amyloid burden.

DISCUSSION: Our findings underscore the importance of LC in AD pathogenesis. Longitudinal measurement of LC degeneration may help distinguish trajectories of age-related cognitive decline and early AD.},
}

@article {pmid41573785,
year = {2025},
author = {Di Nolfi, A and Palermo, V and Palazzesi, I and Passoni, S and Camilli, F and Paggetti, A and Ancidoni, A and Fabrizi, E and Lorenzini, P and Bellomo, G and Sciancalepore, F and Locuratolo, N and Scardetta, P and Giusti, A and Vanacore, N and Zambri, F},
title = {Dementia care from the perspective of family members, caregivers, and public health and social care professionals: a qualitative study of the Italian fund for Alzheimer's and other dementias.},
journal = {Frontiers in public health},
volume = {13},
number = {},
pages = {1726733},
pmid = {41573785},
issn = {2296-2565},
mesh = {Humans ; *Caregivers/psychology ; Italy ; *Dementia/therapy ; Qualitative Research ; Male ; Female ; *Family/psychology ; Focus Groups ; *Public Health ; Aged ; Middle Aged ; COVID-19/epidemiology ; *Health Personnel/psychology ; Adult ; },
abstract = {BACKGROUND: Longer life expectancy has increased the prevalence of dementia, a major cause of disability in old age, requiring an interdisciplinary approach involving health and social care professionals (HScPs) and family members/caregivers (FmCs). This study aims to describe the current state of dementia care in Italy, identifying strengths, weaknesses, and experiences from FmCs and HScPs.

STUDY DESIGN: Descriptive qualitative study.

METHODS: Forty-two focus groups have been conducted with 329 participants (187 HScPs and 142 FmCs).

RESULTS: The management of dementia is hampered by a marked unevenness in territorial services, with often insufficient services and staff. FmCs complain of difficulties in obtaining information and face a burden of care, exacerbated by the fragmentation of services and the COVID-19 pandemic. Despite these critical issues, the support of dementia-specific services (e.g., Centres for Cognitive Disorders and Dementias, Day Care Centres) and associations emerged as crucial. To enhance care, participants emphasized the need for more uniform and integrated services, well-trained professionals, public awareness campaigns to reduce stigma, and increased support for people living with dementia (PLWD) and their families.

CONCLUSION: A holistic and coordinated approach that reduces territorial inequalities and empower effective resources is essential to ensure equitable care and improve the quality of life of PLWD and their families.},
}

Humans
*Caregivers/psychology
Italy
*Dementia/therapy
Qualitative Research
Male
Female
*Family/psychology
Focus Groups
*Public Health
Aged
Middle Aged
COVID-19/epidemiology
*Health Personnel/psychology
Adult

@article {pmid41573740,
year = {2025},
author = {Kumar, V and Beck, S},
title = {Cellular insights into transposable elements in Alzheimer's disease.},
journal = {Frontiers in molecular biosciences},
volume = {12},
number = {},
pages = {1642599},
pmid = {41573740},
issn = {2296-889X},
abstract = {INTRODUCTION: Alzheimer's disease (AD) is a progressive neurodegenerative disorder affecting millions worldwide. While advances in single-cell technologies have elucidated cellular diversity and transcriptional changes in AD, the contribution of transposable elements (TEs) to disease pathogenesis remains poorly understood.

METHODS: We integrated published single-nucleus RNA sequencing data from 11 AD patients and 7 controls with chromatin accessibility profiles from ATAC-seq to map the cell type-specific landscape of TE expression and regulation.

RESULTS: We identified 508 differentially expressed TE loci, 84.3% of which were upregulated in AD, indicating widespread TE activation. TE dysregulation was most prominent in excitatory neurons (319 loci) and oligodendrocytes (165 loci), dominated by SINE (62.8%) and LINE (26.4%) elements. Several dysregulated TEs overlapped regulatory regions near key AD-associated genes including DOC2A, ABCA7, PTK2B, IL34, ABCB9, PLD3, and TARDBP.

DISCUSSION: These findings highlight cell-type-specific TE activation in AD and provide a foundation for investigating TE-mediated regulatory disruption and its therapeutic potential.},
}

@article {pmid41573517,
year = {2025},
author = {Ham, HJ and Park, SS and Lee, YS and Kim, TH and Son, DJ and Kim, JH and Lim, KH and Park, H and Lee, HJ and Yun, J and Han, SB and Choi, MK and Hong, JT},
title = {CHI3L1 monoclonal antibody therapy mitigates cognitive impairment by inhibiting neuroinflammation through ERK and NF-κB pathway in Tg2576 mice.},
journal = {Frontiers in molecular neuroscience},
volume = {18},
number = {},
pages = {1728279},
pmid = {41573517},
issn = {1662-5099},
abstract = {INTRODUCTION: Alzheimer's disease (AD) is neurodegenerative disorder characterized by chronic inflammation in the brain. Chitinase-3-like 1 (CHI3L1), a secreted glycoprotein that is upregulated in a variety of diseases with chronic inflammation, represents a promising target for AD. Here, we studied the inhibitory effect of a novel CHI3L1 monoclonal antibody (H1) on memory impairment and neuroinflammation in Tg2576 transgenic mice.

METHODS AND RESULTS: H1 was shown to cross the blood-brain barrier selectively, as confirmed by fluorescence imaging. Tg2576 mice were administered H1 (2 mg/kg, i.v., weekly for 1 month), and cognitive functions were assessed through behavioral tests. H1 treatment alleviated memory impairment and reduced amyloid deposition and neuroinflammation both in Tg2576 mice and Aβ-induced BV-2 microglial cells. Mechanistically, H1 inhibited the ERK and NF-κB signaling pathways and suppressed M1 microglial marker expression. Global proteomic analysis and gene expression profiling in BV-2 cells and Tg2576 mouse brains revealed a strong association between CHI3L1 and HAX1 expression. H1 therapy significantly reduced HAX1 levels in both in vivo and in vitro models. Moreover, HAX1 induction by Aβ or CHI3L1 was blocked by an NF-κB inhibitor.

DISCUSSION: These findings suggest that CHI3L1 monoclonal antibody therapy may attenuate cognitive decline in AD by modulating neuroinflamma.},
}

@article {pmid41573422,
year = {2026},
author = {Calvo, N and Phillips, N and Bialystok, E and Einstein, G},
title = {Biological sex and bilingualism: Its impact on risk and resilience for dementia.},
journal = {Alzheimer's & dementia (Amsterdam, Netherlands)},
volume = {18},
number = {1},
pages = {e70255},
pmid = {41573422},
issn = {2352-8729},
abstract = {INTRODUCTION: The relationship between biological sex, considered a risk factor for Alzheimer's disease (AD), and bilingualism, a resilience factor, is unclear. We assessed this relationship in 335 individuals with mild cognitive impairment (MCI) in a Canadian cohort.

METHODS: We used univariate analysis and structural equation modelling to study the relationship between female sex and bilingualism. We created a resilience index (RI) for each participant using the residual approach. Logistic and linear regressions predicted cognitive and brain health in relation to RI.

RESULTS: Overall, bilingual males had increased RI. Higher RI was associated with less risk of AD and less neuropathology and glial activation as indexed by plasma p-tau181, neurofilament light, and glial fibrillary acidic protein.

DISCUSSION: In MCI, the combination of elevated estradiol levels due to aromatization and bilingualism may provide synergistic protection for verbal memory, making old bilingual males more resilient.

HIGHLIGHTS: Sex steroids influence verbal memoryIn a structural equation modeling (SEM) model, verbal memory mediates cognitive declineElevated estradiol from aromatization makes old bilinguals more resilient.},
}

@article {pmid41573421,
year = {2026},
author = {Warren, SL and Ahmed, RM and Piguet, O and Foxe, D and Irish, M},
title = {Modeling contributions of cognition and apathy to functional impairment in younger-onset dementia.},
journal = {Alzheimer's & dementia (Amsterdam, Netherlands)},
volume = {18},
number = {1},
pages = {e70249},
pmid = {41573421},
issn = {2352-8729},
abstract = {INTRODUCTION: Overlaps in symptom presentation limits the capacity to predict functional impairment and future care needs in younger-onset dementia syndromes.

METHODS: A general additive model (GAM) was applied to cross-sectional retrospective data from 375 participants with younger-onset dementia; 152 behavioral-variant frontotemporal dementia (bvFTD), 118 Alzheimer's disease (AD), 66 semantic dementia, and 39 progressive nonfluent aphasia (PNFA). This GAM aimed to explore the dynamic interrelationships between established measures of global cognition, apathy, and functional impairment.

RESULTS: Our GAM significantly predicted functional impairment in all syndromes with a high explained variance (59.5%). Cognition and apathy emerged as significant predictors of functional impairment in each syndrome (p-values < .015). These relationships were consistently linear in AD, non-linear in SD, and mixed in bvFTD and PNFA (i.e., cognition linear and apathy non-linear).

DISCUSSION: Our study shows the potential prognostic utility of GAMs for identifying syndrome-specific transition periods across group-level staging's of functional impairment.

HIGHLIGHTS: First study to apply a general additive model to functional impairment in younger-onset dementia.Studied 375 individuals with younger-onset Alzheimer's disease or frontotemporal dementia.Apathy and cognition were significant predictors of functional impairment in all syndromes.This modeling has significant implications for syndrome-specific prognosis and management.},
}

@article {pmid41573383,
year = {2025},
author = {Liu, B and Chen, C and Cai, P and Zhang, J and Yang, L and Chen, X and Ma, X and Jiang, X and Zhang, A and Song, L and Jiang, L},
title = {The alterations in brain network functional gradients and dynamic functional connectivity in Alzheimer's disease: a resting-state fMRI study.},
journal = {Frontiers in aging neuroscience},
volume = {17},
number = {},
pages = {1716076},
pmid = {41573383},
issn = {1663-4365},
abstract = {BACKGROUND AND PURPOSE: Alzheimer's disease (AD), the most common form of dementia worldwide, is characterized by progressive cognitive decline. Extensive evidence from dynamic functional connectivity (dFC) studies has demonstrated unstable functional states, reduced network flexibility, and impaired transitions between large-scale neurocognitive networks across the AD continuum. However, how these temporal abnormalities are embedded within the hierarchical spatial organization of brain networks, as captured by functional gradients (FG), and whether combined FG-dFC metrics can provide mechanistically interpretable and potentially sensitive imaging biomarkers, remain to be elucidated.

METHODS: This study enrolled 46 AD patients who were diagnosed according to the Amyloid/Tau/Neurodegeneration (ATN) biological diagnostic framework and 37 age- and sex-matched healthy controls (HC). All participants underwent resting-state fMRI. Functional gradients were derived using connectivity similarity matrices and diffusion embedding (aligned and standardized), while dFC was estimated with a sliding window approach and clustered into four recurrent states. Group differences were assessed with two-sample t-tests with Gaussian Random Field (GRF) correction. Correlation analyses included ATN biomarkers and cognitive scores. A linear support vector machine (SVM) with leave-one-out cross-validation evaluated classification performance based on significant FG features.

RESULTS: Compared to the healthy controls, AD patients exhibited widespread FG alterations between regions of the Default Mode Network (DMN) and the Sensorimotor Network (SMN). In the first gradient DMN, the left precuneus showed reduced gradient scores, whereas the right medial superior frontal gyrus and bilateral angular gyri were increased. In the first gradient of the SMN, the right supplementary motor area increased while bilateral superior temporal gyri decreased. Second-gradient reductions were confined to two regions: the left postcentral gyrus (SMN) and left middle occipital gyrus (visual network, VIS). The right medial superior frontal gyrus first-gradient score correlated negatively with T-Tau (r = -0.50, P = 0.006) and age (r = -0.36, P = 0.02); the right angular gyrus correlated negatively with age (r = -0.29, P = 0.04); the left precuneus correlated positively with age (r = 0.38, P = 0.009). dFC revealed four recurrent states (27.59, 17.67, 28.27, 26.47% of total occurrences). Relative to HC, AD showed higher FT and MDT in states 1-2 and lower scores in state 3, with NT unchanged, alongside state-dependent bidirectional connectivity changes (fronto-insular-sensorimotor increases; DMN-temporal and visuo-auditory decreases). The SVM achieved an AUC of 0.776, sensitivity 78.26%, specificity 67.57%, and accuracy 73.49%, with the right superior temporal gyrus within SMN first-gradient contributing most.

CONCLUSION: AD is characterized by macro-scale hierarchical disorganization centered on the principal functional gradient, accompanied by reduced cross-state flexibility and state-dependent connectivity abnormalities. The combined functional gradient-dynamic functional connectivity (FG-dFC) analysis provides complementary spatiotemporal insights and reveals imaging features associated with T-Tau levels and age, offering new perspectives on the neuropathological mechanisms of AD and potential imaging biomarkers. Moreover, these network topology and dynamic connectivity metrics may prove useful for monitoring disease progression, evaluating treatment effects, and stratifying patients in future clinical and interventional studies.},
}

@article {pmid41573356,
year = {2026},
author = {de Rijke, TJ and Kaijser, KK and Vasseur, D and Tasköprü, H and Huisman, L and van Gils, AM and Otten, V and Smits, C and Hofman, CS and Kooistra, M and Smets, EM and Engelsma, T and Visser, LN},
title = {Design and development of 'Helder in Gesprek': A tool to support person-centred communication in memory clinics.},
journal = {Digital health},
volume = {12},
number = {},
pages = {20552076251412631},
pmid = {41573356},
issn = {2055-2076},
abstract = {OBJECTIVE: Person-centred communication in memory clinics is essential, but often not optimal. This study aimed to develop a solution that supports people with cognitive complaints in expressing their needs and preferences during memory clinic consultations.

METHODS: Following a human-centred design approach, co-researchers (n = 4 people with dementia) identified a problem statement. This problem was confirmed and elaborated upon via a questionnaire (n = 25) and focus group (n = 18) for triangulation purposes, and in co-design sessions with people with cognitive complaints (n = 3), care partners (n = 2), and clinicians (n = 3). These sessions informed prototype development in collaboration with a design agency. Usability and User eXperience (UX) testing were conducted with people with cognitive complaints (n = 30), care partners (n = 4), and clinicians (n = 17) via think-aloud sessions, interviews, questionnaires, and focus groups.

RESULTS: Co-researchers emphasized the importance of clinicians gaining a holistic understanding of someone's life and circumstances, which was confirmed in the 'triangulation' questionnaire, focus group, and co-design sessions. Co-design resulted in a digital and analogue prototype of 'Helder in Gesprek' ('Clear in Conversation'), a tool to assist people with cognitive complaints in reflecting on what they wish to share with their clinician and facilitate communication during consultations. Usability testing revealed a generally positive attitude toward the prototypes, while also identifying areas for improvement, such as navigation, system feedback, understandability, distinguishable elements, and cognitive overload.

CONCLUSION: Our human-centred design approach informed the design and development of two prototypes of 'Helder in Gesprek'. Usability and UX testing provide directions for re-design and feasibility testing in a real-world setting.},
}

@article {pmid41573343,
year = {2025},
author = {Pelkmans, W and Cacciaglia, R and Kassinopoulos, M and Grau-Rivera, O and Minguillón, C and Molinuevo, JL and Kollmorgen, G and Quijano-Rubio, C and Wilson, RE and Jonaitis, EM and Langhough, RE and Blennow, K and Zetterberg, H and Suárez-Calvet, M and Salvadó, G and Johnson, SC and Gispert, JD},
title = {Neurobiological correlates of longitudinal grey matter volume changes in preclinical Alzheimer's disease.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.64898/2025.12.01.25341227},
pmid = {41573343},
abstract = {BACKGROUND: Structural brain changes during the earliest asymptomatic stages of Alzheimer's disease (AD) remain poorly understood. Previous research in preclinical AD shows heterogeneous findings, reporting both subtle neuronal loss and paradoxical increases in grey matter (GM) volume. This study applies an extensive cerebrospinal fluid (CSF) biomarker panel to better understand the biological processes underlying longitudinal GM changes in cognitively unimpaired (CU) adults, spanning the amyloid/tau (AT) continuum.

METHODS: We analysed data from 627 CU individuals from three longitudinal cohorts (ALFA+, Wisconsin ADRC, WRAP), with repeated MRI (3.5±0.9 years) and baseline CSF biomarkers from the NeuroToolKit panel (Roche Diagnostics). Using non-negative matrix factorization, we decomposed the CSF biomarker levels into six latent components, reflecting amyloid-β (Aβ) pathology, tau-related pathophysiology with synaptic injury, neuroaxonal injury, microglial reactivity, astrocytic reactivity, and cytokine signalling. We tested associations between component weights and voxel-wise longitudinal GM volume changes using single-component and a joint-all components model. Analyses were performed across the full sample and stratified by AT status. Associations with longitudinal cognitive performance (PACC) were assessed using linear mixed-effects models.

RESULTS: The Aβ pathology component was the strongest and most widespread predictor of longitudinal GM atrophy, predominantly in temporal and frontal regions, also when controlling for tau pathophysiology, neuroaxonal injury, or neuroinflammatory components. Higher Aβ pathology scores were also associated with cognitive decline. The component capturing tau-related pathophysiology and synaptic injury initially associated with GM loss but lost significance after accounting for other biomarker components. In contrast, components reflecting microglial reactivity, astrocytic reactivity, and cytokine signalling were associated with longitudinal GM volume increases, with effects varying by AT stage.

CONCLUSIONS: In this large longitudinal sample of asymptomatic individuals, Aβ pathology emerged as the primary contributor to early neurodegeneration and cognitive decline, beyond the effects of tau pathophysiology and neuroaxonal injury. While glial and inflammatory processes may underlie transient GM increases in preclinical AD. A better understanding of these dynamic relationships between structural brain changes and diverse biological pathways at the earliest stages of AD is crucial to inform the development of interventions before irreversible neurodegeneration occurs.},
}

@article {pmid41573340,
year = {2025},
author = {Costa-Rodrigues, D and Leite, JP and Gales, L},
title = {Probing Macromolecular Interactions by Loss of Solvent Content in Protein Crystals: Application to the Amyloid‑β Peptide Binding to Transthyretin.},
journal = {Crystal growth & design},
volume = {25},
number = {10},
pages = {3511-3517},
pmid = {41573340},
issn = {1528-7483},
abstract = {X-ray crystallography is commonly used to determine the structure of protein-protein complexes, revealing the atomic details of the interactions between macromolecules in the crystal. However, this technique has limited application in binary systems characterized by transient or weak interactions. Here, we demonstrate that protein crystals can still provide valuable information in such systems by assessing crystal solvent content. We applied this method to investigate the interaction between transthyretin (TTR) and the amyloid beta (Aβ) peptide, a system of interest due to transthyretin's proposed role in the clearance of Aβ peptide, whose accumulation in the brain is associated with Alzheimer's disease. Soaking TTR crystals separately with Aβ fragments results in distinct reductions of the crystal void volume and highlights the key sequence residues involved in binding to TTR. Our findings indicate that the middle Aβ12-28 fragment interacts more strongly with TTR than the N- and C-terminals. Analysis of the crystal packing and solvent content indicates an equimolar interaction between transthyretin and the Aβ12-28 peptide. This interaction likely involves surface-exposed regions of TTR, such as the thyroxine binding pocket or the dimer pocket.},
}

@article {pmid41573059,
year = {2025},
author = {Ayla, S and Saygi, HI and Sahin, M and Ciftkaya, E and Kilic, A and Pence, S and Bahadori, F and Dolanbay, EG and Elibol, B},
title = {Urtica dioica can regulate autophagy pathway in the rat hippocampal tissue after STZ-induced neurodegeneration.},
journal = {Northern clinics of Istanbul},
volume = {12},
number = {5},
pages = {531-539},
pmid = {41573059},
issn = {2536-4553},
abstract = {OBJECTIVE: Autophagy plays a crucial role in neuroprotection by helping to clear toxic substances, like misfolded proteins. In neurodegeneration, autophagy is impaired leading to the accumulation of harmful proteins that disrupt neuronal function, promote inflammation, and contribute to the degeneration of brain cells. Therefore, because of its anti-inflammatory and anti-oxidative actions, the effects of Urtica dioica (UD) on the proteins of autophagy signaling pathways was studied in the hippocampus of rats with streptozotocin-(STZ) induced neurodegeneration.

METHODS: Neurodegeneration model of rats was induced by intracerebroventricular injection of STZ (3 mg/kg) to observe both cognitive deficits and autophagic dysfunction. Then, the rats in the treatment group were consumed UD at the dose of 50 mg/kg/day for 4 weeks. At the end of 4 weeks, passive avoidance test was applied for cognitive functions and hippocampal tissue of rats were investigated to determine the changes in the proteins related to autophagy by western blotting and immunofluoresecence.

RESULTS: UD treatment slightly attenuated the STZ-induced memory deficiencies in the rats. In addition, an increase in the autophagy was noted by increasing the expression of Beclin, ATG5, and LC3β proteins in the STZ-UD group compared to the STZ group.

CONCLUSION: In summary, UD may be a candidate molecule as a therapeutic strategy to protect neurons in neurodegeneration through increasing autophagy to reduce toxic protein accumulation.},
}

@article {pmid41572755,
year = {2026},
author = {Pandey, SK and Kulshreshtha, A and Mishra, A},
title = {Phosphatidylethanolamine: Structural Component and Beyond.},
journal = {Current molecular medicine},
volume = {},
number = {},
pages = {},
doi = {10.2174/0115665240415642251205104453},
pmid = {41572755},
issn = {1875-5666},
abstract = {Phosphatidylethanolamine (PE) is a major phospholipid in biological membranes and plays essential roles in autophagy, cell signaling, protein function, and membrane integrity. Its dynamic, conical structure supports membrane fluidity and curvature, which are crucial for processes such as signaling, autophagosome formation, membrane fusion, vesicle trafficking, and proper protein folding. Although PE is abundant, its significance for human health and disease has only recently come to light. Altered PE levels or disruptions in its metabolism have been associated with various conditions, including metabolic disorders such as non-alcoholic fatty liver disease (NAFLD), neurodegenerative diseases like Alzheimer's and Parkinson's, and several cancers. PE is synthesized primarily via two pathways: the CDP-ethanolamine (Kennedy) pathway and the mitochondrial phosphatidylserine decarboxylase (PSD) pathway, both of which are critical for maintaining lipid homeostasis. Advances in lipidomics now allow comprehensive profiling of PE species, facilitating the identification of disease-specific lipid biomarkers. This review expands current knowledge on the physiological roles of PE and elucidates mechanisms underlying PErelated lipid dysregulation in human disease.},
}

@article {pmid41572752,
year = {2026},
author = {Panda, SP and Mittal, D and Saraswat, N},
title = {The Interplay between PKC and ELAV4 in the CNS: An Emerging Therapeutic Axis for Dementia Management.},
journal = {CNS & neurological disorders drug targets},
volume = {},
number = {},
pages = {},
doi = {10.2174/0118715273412072251124092504},
pmid = {41572752},
issn = {1996-3181},
abstract = {Alzheimer's disease (AD) is the most prevalent cause of dementia, accounting for 60-80% of all cases and characterized by amyloid beta (Aβ) plaques and tau protein hyperphosphorylation. Among the signaling mechanisms implicated in AD, protein kinase C (PKC) isoforms and neuron-specific embryonic lethal abnormal vision-4 (ELAV4) have gained increasing attention due to their roles in synaptic plasticity, neuroinflammation, and mRNA stability. This review discusses the potential for targeting the PKC-ELAV4 axis to manage dementia. PKC isoforms, including PKC α, δ, and ε, are involved in amyloid-beta (Aβ) processing, tau phosphorylation, and regulation of mitochondrial activities, whereas ELAV4 stabilizes mRNAs that participate in both the degradation of Aβ (e.g., neprilysin) and the synthesis of Aβ (e.g., beta-site amyloid precursor protein cleaving enzyme 1, BACE1). We reviewed 75 papers published over the last 15 years using search terms such as neuroinflammation, synaptic plasticity, mRNA stability in dementia, ELAV, ELAV4, PKC, and PKC isoforms in databases including PubMed, WOS, and Google Scholar. Results were summarized, compared, and research gaps were identified during data collection and interpretation. ELAV4 can influence the processing of amyloid precursor protein (APP), the precursor of the amyloid-beta peptide, a hallmark of AD. Decreased expression of ELAV4 in the hippocampus is associated with dementia. PKC-δ activates c-Jun N-terminal kinase (JNK) expression, releases Beclin-1 from the Bcl2/Beclin-1 complex, and promotes autophagy. Oxidative stress and PKC η regulate the mitogenactivated protein kinase (MAPK) pathway, leading to tau phosphorylation and neuronal death. PKCε activators and ELAV4 inhibitors have positive effects on cognitive function and dementia management by inhibiting neuroinflammation and neuronal apoptosis, while PKC α, β, δ inhibitors may aid in managing different forms of dementia. This review highlights research gaps and proposes future directions for targeting the PKC-ELAV4 axis as a novel strategy in dementia management.},
}

@article {pmid41572710,
year = {2026},
author = {Rajendran, R and Elangovan, E},
title = {Exploring the Neurotherapeutic Potential of Bacillus-derived Macrolactins as NMDAR Antagonists for Alzheimer's disease: Network Pharmacology and Molecular Modeling Insights.},
journal = {Current drug discovery technologies},
volume = {},
number = {},
pages = {},
doi = {10.2174/0115701638443569251205061143},
pmid = {41572710},
issn = {1875-6220},
abstract = {BACKGROUND: The N-methyl-D-aspartate receptor (NMDAR) plays a critical role in regulating excitatory glutamatergic neurotransmission and synaptic plasticity. However, ex-cessive NMDAR activation can lead to increased calcium ion influx, resulting in excitotoxi-city-a key contributor to neurodegenerative diseases. Although current NMDAR inhibitors exist, their clinical use is limited due to adverse effects.

METHODS: This study employed computational screening of Bacillus-derived macrolactins to identify potential NMDAR antagonists. Molecular docking simulations were performed using AMDock v1.5.2 with the AutoDock Vina engine to assess binding affinities to NMDAR (PDB:7SAD). Docked complexes were analyzed for chemical interactions, including polar contacts, using PyMol v2 and Discovery Studio Visualizer v4.5. Pharmacokinetic properties of macrolactins were predicted using Deep-PK. Molecular dynamics simulations via GROMACS assessed complex stability through RMSD, RMSF, radius of gyration (Rg), hy-drogen bond count, and solvent-accessible surface area (SASA). Network pharmacology anal-ysis of macrolactins in Alzheimer's disease (AD) involved mapping target interactions in STRING, importing into Cytoscape, and identifying hub genes using CytoHubba for KEGG pathway enrichment.

RESULTS: Macrolactin F emerged as a promising candidate, exhibiting strong binding affinity (-6.8 kcal/mol) and an estimated Ki of 10.37 μM, outperforming commercial memantine and other macrolactins. Molecular dynamics simulations confirmed the stability and conforma-tional integrity of the Macrolactin F-NMDAR complex. KEGG pathway enrichment analysis highlighted key hub pathways associated with AD, including hsa05010, hsa04725, hsa04722, hsa04071, hsa04068, hsa04150, and hsa04910.

DISCUSSION: The findings suggest that Macrolactin F possesses superior antagonistic activity against NMDAR compared to memantine, supported by molecular docking and dynamic sim-ulations. Network pharmacology analyses indicate that Macrolactin F can modulate critical signaling pathways implicated in AD, including PI3K/Akt/mTOR and MAPK cascades.

CONCLUSION: Computational analyses identify Macrolactin F as a promising preclinical candi-date for developing allosteric NMDAR inhibitors. This aligns with SDG 3 by contributing to potential therapeutics for neurodegenerative diseases such as Alzheimer's disease and supports SDG 10 by promoting accessible interventions to reduce global health disparities.},
}

@article {pmid41572665,
year = {2026},
author = {Eissman, JM and Ma, Y and Qiao, M and Reyes-Dumeyer, D and Piriz, A and Lee, AJ and Lantigua, RA and Medrano, M and Mejia, DR and Honig, LS and Grodstein, F and Bennett, DA and De Jager, PL and Dalgard, CL and Mayeux, R and Vardarajan, BN},
title = {Biological age acceleration associates with Alzheimer's disease plasma biomarker levels.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {1},
pages = {e71005},
doi = {10.1002/alz.71005},
pmid = {41572665},
issn = {1552-5279},
support = {/AG/NIA NIH HHS/United States ; 5R37AG015473/NH/NIH HHS/United States ; R01AG067501/NH/NIH HHS/United States ; P30AG10161//ROS/MAP/ ; P30AG72975//ROS/MAP/ ; R01AG15819//ROS/MAP/ ; R01AG17917//ROS/MAP/ ; U01AG46152//ROS/MAP/ ; U01AG61356//ROS/MAP/ ; },
mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; *Aging/blood/genetics ; *Alzheimer Disease/blood/genetics ; Apolipoprotein E4/genetics ; *Biomarkers/blood ; Cohort Studies ; DNA Methylation ; Hispanic or Latino ; tau Proteins/blood ; },
abstract = {INTRODUCTION: Epigenetic clocks associate with neuropathology and Alzheimer's disease (AD) clinical risk, but findings are mixed regarding whether clocks associate with blood-based biomarkers and in non-European populations.

METHODS: We calculated biological age and age acceleration from blood methylation data in 704 older Hispanic adults and tested associations with clinical diagnosis and antemortem biomarker levels.

RESULTS: Age acceleration was significantly associated with sex, clinical diagnosis, and levels of eight plasma biomarkers, including P-tau217 levels. Additionally, biomarker associations trended more significantly among APOE-ε4 non-carriers. We also identified that methylation levels in CD4 and CD8 T-cell types are associated with age acceleration.

DISCUSSION: We demonstrated that biological age acceleration, measured in blood, in a Hispanic cohort enriched for preclinical individuals, can stratify clinical AD risk and is associated with plasma AD biomarker levels.

HIGHLIGHTS: Blood-based aging clocks associate with Alzheimer's disease plasma biomarker levels. Biological aging appears relevant to pathological aging in apolipoprotein E (APOE) -ε4 non-carriers. Immune T-cell composition relates to biological aging.},
}

Aged
Aged, 80 and over
Female
Humans
Male
Middle Aged
*Aging/blood/genetics
*Alzheimer Disease/blood/genetics
Apolipoprotein E4/genetics
*Biomarkers/blood
Cohort Studies
DNA Methylation
Hispanic or Latino
tau Proteins/blood

@article {pmid41572660,
year = {2026},
author = {Xing, B and Xiaoqing, P and Yan, Z},
title = {Peripheral Indicators of Alzheimer's Disease Pathology in Women With Polycystic Ovary Syndrome: A Case-Control Study.},
journal = {The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques},
volume = {},
number = {},
pages = {1-9},
doi = {10.1017/cjn.2025.10495},
pmid = {41572660},
issn = {0317-1671},
abstract = {BACKGROUND: Emerging evidence suggests that metabolic and hormonal disturbances in polycystic ovary syndrome (PCOS) may increase vulnerability to neurodegenerative disorders. However, the link between PCOS and Alzheimer's disease (AD)-related pathology remains unclear.

METHODS: In this cross-sectional study, plasma levels of β-amyloid (Aβ40, Aβ42), phosphorylated tau (p-tau181), neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) were quantified in women with PCOS and age-matched controls. Homeostasis model assessment of insulin resistance (HOMA-IR), inflammatory cytokines (IL-6, TNF-α) and hormonal parameters were assessed. Mediation and moderation analyses were conducted to explore metabolic and hormonal pathways underlying biomarker alterations.

RESULTS: Among 400 women (200 PCOS, 200 controls), age and BMI were comparable (P > 0.05). Compared with controls, PCOS participants had increased Aβ40, p-tau181, NfL and GFAP, a slightly higher Aβ42, and a lower Aβ42/40 ratio (all P < 0.05). p-tau181 correlated positively with HOMA-IR (r = 0.41) and IL-6 (r = 0.36), while Aβ42/40 ratio correlated negatively with HOMA-IR (r = -0.27). In multivariable analysis, p-tau181 (aOR = 1.34, 95% CI 1.05-1.71), IL-6 (aOR = 1.19) and TNF-α (aOR = 1.14) were independent predictors of insulin resistance. Mediation analysis indicated that HOMA-IR, IL-6 and TNF-α jointly mediated ∼ 71% of the PCOS-p-tau181 association, suggesting a metabolic-inflammatory pathway linking PCOS to AD-related tau pathology.

CONCLUSIONS: PCOS is linked to peripheral markers of early Alzheimer's pathology, largely mediated by insulin resistance and inflammation. PCOS may provide a clinical context to explore metabolic-inflammatory contributors to early neurodegenerative changes.},
}

@article {pmid41572624,
year = {2026},
author = {Bräuer, S and Sondermann, V and Schniewind, I and Hähnel, T and Dinter, E and Kleineidam, L and Stark, M and Schmid, M and Sodenkamp, S and Laske, C and Spruth, E and Priller, J and Janowitz, D and Bürger, K and Kilimann, I and Teipel, S and Storch, A and Hansen, N and Wiltfang, J and Glanz, W and Düzel, E and Preis, L and Peters, O and Hellmann-Regen, J and Wagner, M and Bernhardt, A and Levin, J and Petzold, G and Kronmüller, M and Gamez, A and Spottke, A and Brosseron, F and Rostamzadeh, A and Jessen, F and Hermann, A and Fliessbach, K and Schneider, A and Falkenburger, BH},
title = {Alpha-synuclein quantitative seed amplification assay predicts conversion to dementia.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {1},
pages = {e71167},
doi = {10.1002/alz.71167},
pmid = {41572624},
issn = {1552-5279},
support = {//Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden/ ; //Deutsches Zentrum für Neurodegenerative Erkrankungen e.V. (DZNE)/ ; },
mesh = {Humans ; *alpha-Synuclein/cerebrospinal fluid ; Male ; Female ; *Dementia/cerebrospinal fluid/diagnosis ; Aged ; Disease Progression ; Biomarkers/cerebrospinal fluid ; Aged, 80 and over ; Lewy Body Disease/cerebrospinal fluid ; Prognosis ; Cohort Studies ; },
abstract = {INTRODUCTION: The alpha-synuclein seed amplification assay (SAA) has shown excellent performance in the detection of Lewy body pathology in cerebrospinal fluid (CSF). Lewy body pathology is prognostically relevant in patients at risk for dementia. Current assays only provide binary results, so there is a need to quantify the extent of pathology in living patients.

METHODS: In addition to the "standard" SAA, we developed a quantitative SAA (qnSAA) and measured 432 CSF samples (216 baseline-follow-up pairs).

RESULTS: qnSAA results correlated with cognitive performance. Seventy-five percent of participants with fast qnSAA kinetics converted to dementia in the observed interval. Overall, participants with fast qnSAA kinetics accounted for 27.3% of dementia converters in the entire cohort.

DISCUSSION: Findings demonstrate promising properties of qnSAA measurements in a cohort of patients at risk for dementia. qnSAA results showed improved prognostic relevance and have potential to measure target engagement of therapies against Lewy body pathology.},
}

Humans
*alpha-Synuclein/cerebrospinal fluid
Male
Female
*Dementia/cerebrospinal fluid/diagnosis
Aged
Disease Progression
Biomarkers/cerebrospinal fluid
Aged, 80 and over
Lewy Body Disease/cerebrospinal fluid
Prognosis
Cohort Studies

@article {pmid41572619,
year = {2026},
author = {Montero-Calle, A and Coronel, R and Manosalva, J and Megías, D and de Los Ríos, V and Rábano, A and Peláez-García, A and Martínez-Useros, J and Fernández-Aceñero, MJ and Liste, I and Barderas, R},
title = {Comprehensive profiling of Aβ40 and Aβ42 fibril-interacting proteins reveals PRKCG as a drug-targetable regulator of amyloidogenesis in Alzheimer's disease.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {1},
pages = {e71090},
doi = {10.1002/alz.71090},
pmid = {41572619},
issn = {1552-5279},
support = {FPU predoctoral contract//Ministerio de Educación y Formación Profesional/ ; Predoctoral grant//Fundación Tatiana Pérez de Guzmán el Bueno/ ; PID2021-126715OB-I00//Ministerio de Ciencia e Innovación/ ; PMP22/00084//AES-ISCIII/ ; PI17CIII/00045//AES-ISCIII/ ; },
mesh = {*Amyloid beta-Peptides/metabolism ; Humans ; *Alzheimer Disease/metabolism/pathology ; *Peptide Fragments/metabolism ; Proteomics ; *Plaque, Amyloid/metabolism/pathology ; *Protein Kinase C/metabolism ; Male ; Aged ; Female ; },
abstract = {INTRODUCTION: Proteins interacting with amyloid beta (Aβ) fibrils could be key to plaque formation in Alzheimer's disease (AD) and represent potential biomarkers and therapeutic targets. Previous proteomic studies using microdissected plaques might have captured non-specific components rather than true Aβ interactors.

METHODS: Biotinylated Aβ40 or Aβ42 peptides were induced to form fibrils, with Scrambled peptides as controls, and incubated with protein extracts from AD and control prefrontal cortex tissue. Pull-down assays coupled with label-free proteomics identified fibril interactors. Dysregulation and localization were assessed by Western blot, immunofluorescence, immunocytochemistry, immunohistochemistry, and in silico analyses.

RESULTS: We identified 185 Aβ40- and 874 Aβ42-associated proteins, with 78 shared. Sixteen proteins, including protein kinase C gamma type (PRKCG), displaying altered expression in AD, were validated as actual interactors and plaque components ex vivo. Remarkably, modulation of PRKCG influenced fibril formation.

DISCUSSION: This study expands the Aβ plaque-associated proteome, identifies novel interactors, and highlights PRKCG as a drug-targetable regulator of AD amyloidogenesis.

HIGHLIGHTS: A comprehensive proteomic profiling allowed identifying proteins interacting with Aβ40 and Aβ42 fibrils, including many novel interactors. Sixteen proteins were validated in vitro and ex vivo as bona fide Aβ plaque constituents. Dysregulated expression of key interactors was confirmed in AD brain and cell models. Modulation of PRKCG activity altered Aβ fibril formation and progression. Findings expand the Aβ-associated proteome and highlight novel targets for AD biomarker and therapeutic development.},
}

*Amyloid beta-Peptides/metabolism
Humans
*Alzheimer Disease/metabolism/pathology
*Peptide Fragments/metabolism
Proteomics
*Plaque, Amyloid/metabolism/pathology
*Protein Kinase C/metabolism
Male
Aged
Female

@article {pmid41572511,
year = {2026},
author = {Arias, JJ and Nielsen, KE and Bolcic-Jankovic, D and Bonham, LW and Campbell, EG and Lah, JJ and Manchester, MA and Scipion, CEA and Wang, Y and Wolf, LE and Mello, MM and Yokoyama, JS},
title = {Data sharing practices and experiences among Alzheimer's disease and related dementia researchers.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {1},
pages = {e71046},
doi = {10.1002/alz.71046},
pmid = {41572511},
issn = {1552-5279},
support = {1R01AG080093/AG/NIA NIH HHS/United States ; T32EB001631//NIH)-/ ; RR24-217//RSNA) R&E Foundation/ ; R01AG062588//NIH-NIA/ ; R01AG057234//NIH-NIA/ ; P30AG062422//NIH-NIA/ ; P01AG019724//NIH-NIA/ ; U19AG079774//NIH-NIA/ ; U54NS123985)//NIH-National Institute of Neurological Disorders and Stroke/ ; 1R01AG080093//Foundation for the National Institutes of Health/ ; },
mesh = {Humans ; *Information Dissemination ; *Alzheimer Disease ; Cross-Sectional Studies ; *Research Personnel ; United States ; Surveys and Questionnaires ; *Dementia ; Female ; Male ; *Biomedical Research ; },
abstract = {INTRODUCTION: Data sharing among investigators of Alzheimer's disease and related dementias (ADRD) allows for representative datasets, supports reproducibility, and increases rigor. Yet limited evidence on investigators' practices and experiences precludes solutions that promote optimal practices.

METHODS: A cross-sectional survey of US-based ADRD investigators with National Institutes of Health awards funded between 2016 and 2019.

RESULTS: Among 585 respondents (response rate of 64.5%), 62.9% were engaged in data sharing in the previous 5 years. Among data requesters, 61.8% reported that all requests were fulfilled within 6 months. Among those who received requests, 85.1% reported fulfilling all requests. Reasons for declining requests included existing data use agreement requirements, Institutional Review Board standards, and resource limitations. Respondents who shared data reported positive consequences (e.g., developing collaborations) more often than negative (e.g., being "scooped").

DISCUSSION: Data sharing behaviors among ADRD researchers are encouraging. Nevertheless, addressing remaining barriers could help avoid the negative consequences of data requests not being fulfilled.

HIGHLIGHTS: Data sharing is critical to advancing research in ADRD. Investigators are engaged in data sharing through initiating or receiving requests. Most data requests initiated or received by ADRD investigators are fulfilled. Investigators who fulfill requests report positive experiences with sharing data. Delay or decline of requests can result in consequences that impede research.},
}

Humans
*Information Dissemination
*Alzheimer Disease
Cross-Sectional Studies
*Research Personnel
United States
Surveys and Questionnaires
*Dementia
Female
Male
*Biomedical Research

@article {pmid41572497,
year = {2026},
author = {Cao, SQ and Jiménez-Loygorri, JI and Qiu, Y and Kang, YJ and Do, KV and Smith, AE and Huang, J and Pan, JP and Mao, L and Li, A and Yang, H and Aman, Y and Lagartos, MJD and Lautrup, SH and Chen, A and Liang, KX and Zhang, H and Yi, J and Jin, X and Cheung, TC and Apokotou, O and Papastefanaki, F and Matsas, R and McEwan, WA and Cheng, F and Cho, H and Chen, G and Su, H and Palikaras, K and Luo, OJ and Zhao, QH and Ding, D and van Duijn, C and Tavernarakis, N and Boya, P and Tencomnao, T and Fang, EF},
title = {The Mitochondrial Guardian α-Amyrin Mitigates Alzheimer's Disease Pathology via Modulation of the DLK-SARM1-ULK1 Axis.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {},
number = {},
pages = {e12374},
doi = {10.1002/advs.202512374},
pmid = {41572497},
issn = {2198-3844},
support = {#282942//Molecule AG/VITADAO/ ; (#262175//Research Council of Norway/ ; #334361//Research Council of Norway/ ; #119986//NordForsk Foundation/ ; #281931//Civitan Norges Forskningsfond for Alzheimers sykdom/ ; #TO01000215//Czech Republic-Norway KAPPA programme/ ; #101073251//HORIZON-TMA-MSCA-DN/ ; #104617//Wellcome Leap's Dynamic Resilience Program/ ; PRE2019-088222//FPI fellowship from MCIN/ ; #82301422//Natural Science Foundation of China/ ; 82301422//Natural Science Foundation of China/ ; #82473701//Natural Science Foundation of China/ ; #82371429//Natural Science Foundation of China/ ; #82173599//Natural Science Foundation of China/ ; 19656//Fondation Santé/ ; GA695190-MANNA/ERC_/European Research Council/International ; NRF-2020R1A2C2010285//National Research Foundation/ ; NRF-I21SS7606036//National Research Foundation/ ; HU22C0115//Ministry of Health & Welfare and Ministry of Science and ICT/ ; NRF-2022R1I1A1A01063094//Ministry of Health & Welfare and Ministry of Science and ICT/ ; #82301422//National Natural Science Foundation of China/ ; 82301422//National Natural Science Foundation of China/ ; #82473701//National Natural Science Foundation of China/ ; 82301422//National Natural Science Foundation of China/ ; #82473701//National Natural Science Foundation of China/ ; #82173599//National Natural Science Foundation of China/ ; 310030-215271//Swiss National Science Foundation (SNSF)/ ; 2022B1515120043//Basic and Applied Basic Research Foundation of Guangdong Province/ ; #43622//Nasjonalforeningen for Folkehelsen/ ; #269901//Akershus Universitetssykehus/ ; #261973//Akershus Universitetssykehus/ ; #262960//Akershus Universitetssykehus/ ; RS-2024-00336758//National Research Foundation of Korea (NRF)/ ; #HFRI-1019//Hellenic Foundation for Research and Innovation grant DiseasePhenoTarget./ ; //Chulalongkorn University to commemorate 72nd Anniversary of his Majesty King Bhumibol Adulyadej/ ; //The 100th Anniversary Chulalongkorn University Fund for Doctoral Scholarship/ ; //The 90th Anniversary Chulalongkorn University Fund (Ratchadaphiseksomphot Endowment Fund) and Overseas Research Experience scholarship for Graduate students/ ; PID2021-126864NB-I00//MCIN/ ; },
abstract = {High consumption of colorful fruits and vegetables correlates with low dementia risk, but the exact molecules and the underlying biological mechanisms governing their bioactive profiles are largely unknown. Using a 10-year observational cohort study coupled with an AI-driven systems pharmacology platform, we identified a natural triterpenoid compound found in colorful fruits and vegetables, α-Amyrin (αA), as a therapeutic candidate for Alzheimer's disease (AD). The efficacy of αA in treating the symptoms of AD, such as Tau tangles, damaged mitochondria, and memory loss, was examined using cross-species models; αA retained memory in AD-like animal models while also strongly inhibiting Tau pathology, especially p-Tau217, in a cellular 'Tau seeding' system and in Tau[P301S] mice, followed by validation using a human 3D microfluidic system. At molecular level, αA is a robust mitochondrial regulator, enhancing mitochondrial stress resilience and activation of mitophagy. Mechanistically, αA inhibits dual leucine zipper kinase (DLK), leading to the inhibition of DLK-Sterile Alpha and TIR Motif Containing 1 (SARM1)-dependent neurodegeneration; this inhibition frees unc-51 Like Autophagy Activating Kinase 1 (ULK1) from the ULK1-SARM1 complex, allowing it to participate in autophagy/mitophagy. αA also shows strong translational potential with a 10.1 h half-life and the ability to cross the blood-brain barrier. Our results indicate that αA may act as a mitochondrial guardian against AD via modulating the DLK-SARM1-ULK1-autophagy/mitophagy axis while further preclinical and clinical studies are warranted.},
}

@article {pmid41572495,
year = {2026},
author = {Zaman, A and Drake, SS and Fournier, AE},
title = {Extracellular Vesicle-Derived microRNAs as Fluid Biomarkers in Neurodegenerative Diseases: A Systematic Review.},
journal = {Journal of neurochemistry},
volume = {170},
number = {1},
pages = {e70323},
doi = {10.1111/jnc.70323},
pmid = {41572495},
issn = {1471-4159},
support = {//MS Canada/ ; /CAPMC/CIHR/Canada ; //Fonds de Recherche du Québec - Santé/ ; //Myelin Repair Foundation/ ; //Fonds de recherche du Québec/ ; },
mesh = {Humans ; *Neurodegenerative Diseases/diagnosis/genetics/cerebrospinal fluid/blood/metabolism ; *Extracellular Vesicles/metabolism/genetics ; *MicroRNAs/cerebrospinal fluid/metabolism/blood ; Biomarkers/cerebrospinal fluid/blood/metabolism ; Animals ; },
abstract = {Given the absence of curative treatments for neurodegenerative diseases, early detection and therapeutic intervention are critical to slowing disease progression. Extracellular vesicles (EVs) have emerged as promising biomarkers for neurodegeneration, owing to their accessibility in bodily fluids and dynamic molecular cargo, including microRNAs (miRNAs). The last decade has seen accumulating evidence for miRNA dysregulation in circulating EVs from people with neurodegenerative diseases; however, assessing reproducibility between studies remains challenging, largely due to clinical and methodological heterogeneity. In this systematic review, we comprehensively searched the MEDLINE database for studies investigating miRNA expression in biofluids from people with neurodegenerative diseases. We extracted miRNA expression data from 185 peer-reviewed publications, published until June of 2025, reporting altered miRNA levels in fluid-derived EVs from people with neurodegenerative diseases. We consolidated results between studies to identify the most frequently dysregulated miRNAs across diseases, with a focus on Alzheimer's disease, Parkinson's disease, mild cognitive impairment, multiple sclerosis, amyotrophic lateral sclerosis, frontotemporal dementia, stroke, traumatic brain injury, and schizophrenia. Evaluating tissue specificity of frequently dysregulated miRNAs revealed enrichment of select miRNAs in the nervous system relative to blood and immune compartments. Summarizing miRNA regulation across biofluids emphasized consistencies between cerebrospinal fluid and plasma, but not serum. We highlight circulating miRNAs that may be reflective of neuropathology, including miR-143-3p, miR-127-3p, miR-9-5p, miR-15a-5p, and miR-125b-5p. Finally, we provide a repository of miRNA expression data from over 30 neurodegenerative conditions which can be exploited to further investigate miRNA regulation in diseases of interest.},
}

Humans
*Neurodegenerative Diseases/diagnosis/genetics/cerebrospinal fluid/blood/metabolism
*Extracellular Vesicles/metabolism/genetics
*MicroRNAs/cerebrospinal fluid/metabolism/blood
Biomarkers/cerebrospinal fluid/blood/metabolism
Animals

@article {pmid41572435,
year = {2026},
author = {Yan, J and Tang, Z and Luo, Y and Liu, B and Huang, X and Wei, J and Yue, F},
title = {Islet Amyloid Polypeptide Modelled to Simulate Diabetes Co-Oligomerized with β-Amyloid 1-42 Reproducing the Pathological Cascade of Alzheimer's Disease in Human Cerebral Organoids.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {},
number = {},
pages = {e16837},
doi = {10.1002/advs.202516837},
pmid = {41572435},
issn = {2198-3844},
support = {2021ZD0200900//STI2030-Major Projects/ ; XTCX2022JKC05//Project of Collaborative Innovation Center of One Health/ ; },
abstract = {Previous animal models of sporadic Alzheimer's disease (sAD), based on the β-amyloid (Aβ) cascade hypothesis and induced by Aβ1-42 oligomers (AβO), only recapitulated early AD pathological features. sAD cerebral organoids (COs) model employed Aβ coculture approach and found no typical features of AD pathology. Type 2 diabetes (T2DM) is one of the most important modifiable AD risk factors, so we hypothesize that T2DM could substantially exacerbate Aβ neurotoxicity and reproduce typical AD pathology. Human islet amyloid polypeptide (hIAPP) was used to mimic T2DM and was co-oligomerized with Aβ1-42 peptide, and delivered to the central of human iPSC-derived mature COs through intermittently repeated microinjections, so as to simulate the chronic exposure to Aβ within the brain. The Aβ42-hIAPP co-oligomers induced a pathological phenotype more closely resembling the pathological features of advanced AD, notably, neuronal density showed significant reduction, with 3.2 times more neuronal death. Dynamic metabolomic analysis revealed the metabolic pathways and differential metabolites that may be correlated to the primary mechanism underlying the enhanced neurotoxic effects and accelerated AD pathology. Furthermore, this study developed a sAD CO model more resembling the pathological features of advanced AD, which potentially provides a valuable platform for AD pathogenesis research and novel drug screening.},
}

@article {pmid41572310,
year = {2026},
author = {Kashem, M and Haldenby, O and Ahmad, JF and Muhammad, AA and Mostert, CM and Ali, S},
title = {Are diagnostic technologies for alzheimer's disease and dementia cost-effective? A systematic review of economic evaluations.},
journal = {Alzheimer's research & therapy},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13195-025-01933-1},
pmid = {41572310},
issn = {1758-9193},
abstract = {BACKGROUND: Alzheimer's disease (AD) and dementia pose a significant clinical and economic burden globally. Early diagnosis and intervention can potentially delay disease progression. Current diagnostic guidelines recommend considering imaging and biomarker analysis in conjunction with clinical evaluation. Given limited healthcare resources, evidence on the cost-effectiveness of diagnostic technologies is critical to guide allocation of resources.

OBJECTIVE: To systematically review the economic evaluation studies of neuroimaging, biomarkers, and other diagnostic or screening strategies for diagnosing and/or tracking the progression of AD or dementia.

METHODS: A comprehensive search was conducted across Medline, Embase, PsycINFO, CINAHL and EconLit, and to identify relevant studies, with no restrictions on country, language, or publication period. Quality of the studies was evaluated using the Consensus on Health Economic Criteria-Extended (CHEC-Extended) checklist.

RESULTS: Out of 6,804 records, 21 studies met the eligibility criteria. These included evaluations of neuroimaging technologies such as Positron Emission Tomography, Single Photon Emission Computed Tomography, Computed Tomography, and Magnetic Resonance Imaging (n = 10), cerebrospinal fluid and blood biomarkers (n = 7), and alternative diagnostic strategies including screening programs, machine learning-based models, and multidisciplinary care approaches (n = 4). Among the studies evaluating imaging technologies, most (n = 6) did not find them to be cost-effective. In contrast, CSF and blood biomarker studies found these technologies to be cost-effective, with some variability in results. Methodological quality score ranged between 15% and 95%, indicating a mix of low- to high-quality studies. Due to heterogeneity in study designs and reported outcomes, direct comparisons were not feasible.

CONCLUSIONS: While many studies were of high quality, heterogeneity in study objectives, design, and outcomes restricted evidence synthesis. Future research should ensure methodological consistency, transparent cost reporting, and integration of new treatment frameworks to improve the policy relevance and reliability of economic evidence for AD diagnostics.},
}

@article {pmid41572298,
year = {2026},
author = {Pareja-Navarro, KA and King, CD and Kauwe, G and Ngwala, YY and Lokitiyakul, D and Wong, I and Vira, A and Liu, Y and Chen, JH and Sharma, M and Navarro, G and Malak, O and Zhou, C and Schilling, B and Tracy, TE},
title = {Tau oligomers modulate synapse fate by eliciting progressive bipartite synapse dysregulation and synapse loss.},
journal = {Molecular neurodegeneration},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13024-026-00928-2},
pmid = {41572298},
issn = {1750-1326},
support = {T32AG00026624//National Institutes of Health, United States/ ; R01AG070193//National Institutes of Health, United States/ ; R21AG077556/NH/NIH HHS/United States ; AARFD-21-850893/ALZ/Alzheimer's Association/United States ; },
}

@article {pmid41571964,
year = {2026},
author = {Ran, S and Zhang, J and Cai, M and Chen, L and Qian, Z and Tian, F and Wu, G and Boyd, R and McMillin, SE and Zeng, HC and Yang, Y and Lin, H},
title = {Associations of air pollution and genetic risk and their interaction with risk of Alzheimer's disease: identification of risk loci and potential biological pathways.},
journal = {GeroScience},
volume = {},
number = {},
pages = {},
pmid = {41571964},
issn = {2509-2723},
support = {2023-GKLEH-01//Guangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Health, Guilin Medical University/ ; 2024A1515010465//Basic and Applied Basic Research Foundation of Guangdong Province/ ; },
abstract = {BACKGROUND: Air pollution is associated with Alzheimer's disease (AD), and the susceptibility of AD from air pollution may be affected by genetic characteristics, but the underlying mechanisms remain unknown.

METHODS: Data from the UK Biobank, in conjunction with PLINK2, was utilized to conduct a genome-wide analysis of a gene-air pollution (PM2.5, PM10, NO2, and NOx) interaction in AD. Functional annotation, positional gene mapping, expression Quantitative Trait Loci (eQTL) analysis, 3D chromatin interactions mapping (ciMap), and gene expression analysis were conducted using FUMA. Potential biological pathways was analyzed by Metascape.

RESULTS: A total of 322,958 participants were included in the study. Genome-wide gene-air pollution interaction analysis (GWIA) identified 38, 36, 66, and 101 genomic risk loci that interacted with PM2.5, PM10, NO2 and NOx (p < 5 × 10[-8]). The functional annotation positional gene mapping, eQTL, ciMap mapping, and quantitative gene prioritization prioritized 26, 25, 46 and 70 prioritized genes for PM2.5, PM10, NO2 and NOx, including PTCH1, UNC80, TUBGCP3, RUNX2, RCAN2, SUPT3H, DNPH1, TTBK1, and RSPH9, and we found significantly high expression of NOx-related prioritized genes in the heart atrial appendage, the modulation of smoothened signaling was associated with PM2.5 and PM10, hemopoiesis was associated with nitrogen oxides, and learning or memory processes may be involved in the interaction between PM2.5, NO2, NOx, and genes, affecting Alzheimer's disease.

CONCLUSIONS: We prioritized genetic risk loci that interact with air pollutants in AD and revealed that learning or memory are crucial pathways through which these pollutants interact with genes PDE1B, SRF, ZNF385A, and TTBK1.},
}

@article {pmid41571954,
year = {2026},
author = {Ahn, NH and Hong, SC and Hong, CR and Lee, EH and Lee, JH and Choi, SB and Jung, J and Kim, Y and Kim, JS and Park, K and Kim, YK and Kim, Y and Yang, SH},
title = {Fucoxanthin Extracted from the Microalgae Phaeodactylum tricornutum Ameliorates Alzheimer's Pathologies with the Reduction of Aβ-Induced NLRP3 Inflammasome Activation in APP/PS1 Mice.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {385},
pmid = {41571954},
issn = {1559-1182},
mesh = {Animals ; *Alzheimer Disease/drug therapy/pathology/metabolism ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; *Xanthophylls/pharmacology/therapeutic use/isolation & purification ; *Amyloid beta-Peptides/metabolism ; Mice, Transgenic ; *Inflammasomes/metabolism ; Mice ; *Microalgae/chemistry ; Microglia/drug effects/metabolism ; Mice, Inbred C57BL ; Astrocytes/drug effects/metabolism/pathology ; tau Proteins/metabolism ; *Presenilin-1/metabolism ; Male ; *Amyloid beta-Protein Precursor/metabolism ; Brain/pathology/drug effects/metabolism ; },
abstract = {Alzheimer's disease (AD) is a progressive neurodegenerative disorder, one of the most common types of dementia, accompanying severe learning and memory dysfunctions. In AD brains, the misfolded aggregation and deposits of amyloid-β (Aβ) and tau are frequently observed before the cognitive symptom onset; thus, trials for alleviation of these lesions are considered commensurate strategies with AD treatment. Additionally, increasing evidence suggests that misfolded and aggregated proteins induce the activation of microglia and astrocytes by the release of the inflammatory mediators via the activation of the inflammatory signaling cascade, which consequently contributes to AD pathogenesis. Here, we investigated the therapeutic potential of fucoxanthin, a compound derived from the microalgae Phaeodactylum tricornutum, in mitigating AD pathologies. Fucoxanthin was shown to inhibit the aggregation of Aβ and tau, converting their aggregates to monomeric forms. In the brain of APP/PS1 transgenic mice, fucoxanthin administration significantly reduced the levels of Aβ plaques and hyperphosphorylated tau and further ameliorated cognitive impairments by inhibiting the activation of microglia and astrocytes. Notably, fucoxanthin effectively regulated Aβ-induced NLRP3 inflammasome activation in astrocytes, reducing neuroinflammation associated with AD. Thus, our findings showing the multifaceted therapeutic mode of action of fucoxanthin against AD provide that fucoxanthin would have promising roles in the strategies of AD treatment.},
}

Animals
*Alzheimer Disease/drug therapy/pathology/metabolism
*NLR Family, Pyrin Domain-Containing 3 Protein/metabolism
*Xanthophylls/pharmacology/therapeutic use/isolation & purification
*Amyloid beta-Peptides/metabolism
Mice, Transgenic
*Inflammasomes/metabolism
Mice
*Microalgae/chemistry
Microglia/drug effects/metabolism
Mice, Inbred C57BL
Astrocytes/drug effects/metabolism/pathology
tau Proteins/metabolism
*Presenilin-1/metabolism
Male
*Amyloid beta-Protein Precursor/metabolism
Brain/pathology/drug effects/metabolism

@article {pmid41571882,
year = {2026},
author = {Laczó, M and Maleninska, K and Khazaalova, N and Borovska, S and Vyhnalek, M and Hort, J and Stuchlik, A and Svoboda, J and Laczó, J},
title = {Spatial pattern separation deficits in early Alzheimer's disease are comparable in humans and animal models.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-36266-y},
pmid = {41571882},
issn = {2045-2322},
support = {40125//Grant Agency of Charles University/ ; 22-33968S//Czech Science Foundation/ ; 21-16667K//Czech Science Foundation/ ; LX22NPO5107//National Institute for Neurological Research (Programme EXCELES)/ ; 00064203//Ministry of Health of the Czech Republic - conceptual development of research organization, University Hospital Motol, Prague, Czech Republic grant/ ; 6980382//Institutional Support of Excellence 3 2. LF UK/ ; NW25-04-00337//Ministry of Health of the Czech Republic/ ; },
abstract = {Spatial pattern separation (SPS) is a memory process that enables the discrimination of similar spatial locations. This process is vulnerable to pathophysiological changes in the early stages of Alzheimer's disease (AD), but the translational potential of its testing remains unclear. This study aimed to evaluate the potential of SPS testing as a translational cognitive marker for identifying early AD and enabling direct comparisons of cognitive outcomes in animals and humans. We used a validated SPS task to examine biomarker-defined participants with amnestic mild cognitive impairment due to AD (AD aMCI; n = 56) and cognitively normal (CN) participants (n = 60). An animal version of this task, based on a modified Morris Water Maze task, was used to test six-month-old transgenic TgF344-AD rats (n = 38) and wild-type (WT) rats (n = 36). AD aMCI participants performed worse than CN participants, with performance declining as distance decreased. These results remained unchanged when adjusted for memory performance. TgF344-AD rats performed worse than WT rats in a probe trial with a 90° SPS design, but not in probe trials with an 180° SPS design or no SPS demands. The discriminatory power of the task was similar in the human and animal experiments. The findings demonstrate comparable SPS deficits in the early stages of AD in both humans and rodent models, which are not attributable to general memory impairment. SPS testing enables direct comparisons to be made between the cognitive performance of rats and humans, making it a promising approach for translational AD research.},
}

@article {pmid41571873,
year = {2026},
author = {Wilson, C and Galeano, P and Remedi, MM and Novack, GV and Campanelli, L and Gastaldi, L and Miglietta, E and Rossi, AH and Olivar, N and Brusco, LI and Castaño, EM and Cáceres, A and Morelli, L},
title = {Mitochondrial dysfunction and Ca[2+] dysregulation in human iPSC-derived neurons carrying presenilin-1 mutation arise under stress via an MCU-1-independent mechanism.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-35597-0},
pmid = {41571873},
issn = {2045-2322},
support = {PICT-2015-0285 and PICT-2016-4647//Agencia Nacional de Promoción de la Investigación, el Desarrollo Tecnológico y la Innovación/ ; PIBT/09-2013//Agencia Nacional de Promoción de la Investigación, el Desarrollo Tecnológico y la Innovación/ ; PIBT/09-2013, PICT-2015-0285 and PICT-2016-4647//Agencia Nacional de Promoción de la Investigación, el Desarrollo Tecnológico y la Innovación/ ; },
}

@article {pmid41571845,
year = {2026},
author = {Pournajaf, S and Baerz, MM and Khoshsirat, S},
title = {The mTOR Pathway in Hearing Disorders: Mechanistic Links to Aging, Regeneration, and Neurodegeneration.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {388},
pmid = {41571845},
issn = {1559-1182},
mesh = {*TOR Serine-Threonine Kinases/metabolism ; Humans ; *Aging/metabolism/pathology ; Animals ; *Signal Transduction/physiology ; *Hearing Disorders/metabolism/pathology ; *Regeneration/physiology ; *Neurodegenerative Diseases/metabolism/pathology ; *Nerve Degeneration/metabolism/pathology ; },
abstract = {Hearing loss is a prevalent global health problem that most often arises from aging, noise exposure, ototoxic insults, or genetic defects. In addition to its well‑recognized social and economic burden, mounting evidence links hearing loss to neurological disorders such as Alzheimer's disease and dementia, underscoring the urgent need for effective curative strategies. Progress in regenerative therapies has been hindered by the limited capacity of mammalian auditory hair cells to regenerate, making a deep understanding of the underlying molecular pathology essential. The mechanistic target of rapamycin (mTOR), a master regulator of cell growth, metabolism, autophagy, and aging, has recently emerged as a key player in both auditory and neurological disorders. In this review, we summarize the current knowledge on how mTOR signaling shapes auditory cellular physiology, contributes to hearing disorder pathogenesis, and offers novel therapeutic entry points. We further explored the possibility that dysregulated mTOR activity may represent a missing mechanistic link between hearing loss and broader neurological disease processes.},
}

*TOR Serine-Threonine Kinases/metabolism
Humans
*Aging/metabolism/pathology
Animals
*Signal Transduction/physiology
*Hearing Disorders/metabolism/pathology
*Regeneration/physiology
*Neurodegenerative Diseases/metabolism/pathology
*Nerve Degeneration/metabolism/pathology

@article {pmid41571818,
year = {2026},
author = {Ledford, H},
title = {Cancer might protect against Alzheimer's - this protein helps explain why.},
journal = {Nature},
volume = {},
number = {},
pages = {},
pmid = {41571818},
issn = {1476-4687},
}

@article {pmid41571775,
year = {2026},
author = {Sathish, R and Muthukumar, R and Kumaran, KM and Murugan, SP},
title = {Intelligent decision-making systems for early detection of alzheimer's disease using wearable technologies and deep learning.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-36895-3},
pmid = {41571775},
issn = {2045-2322},
abstract = {Intelligent decision-making systems using wearable electronics and deep learning (DL) might identify Alzheimer's disease (AD) early for treatment. These technologies can continually monitor vital signs and behavioral characteristics to identify early cognitive deterioration in patients. Clinical examinations, neuroimaging, and cognitive testing are the main ways to identify Alzheimer's, but they are difficult, expensive, and frequently miss the illness early on. Such approaches lack the sensitivity and real-time monitoring essential for early intervention. Through wearable technology and sophisticated DL approaches, Early Detection using Deep Learning Algorithm (ED-DLA) tackles these constraints. In real time, wearable sensors capture data on heart rate, sleep habits, and physical activity. DL algorithms evaluate this data to identify early Alzheimer's. Continuous and non-invasive monitoring improves detection sensitivity and accuracy. To evaluate sequential wearable device data, the suggested technique uses an RNN-based image classification model. Temporal patterns are essential for understanding AD development, and the RNN does so well. The slight changes in cognitive and physical activities may indicate early-stage dementia. The suggested AD diagnosis and management system improves early detection accuracy and real-time monitoring, making it more dependable and scalable.},
}

@article {pmid41571708,
year = {2026},
author = {Chen, Y and Zeng, X and Olvera-Rojas, M and Sewell, KR and Sehrawat, A and Gu, J and Triviño-Ibañez, EM and Solis-Urra, P and Gómez-Río, M and Oberlin, LE and Kramer, AF and Hillman, CH and Burns, JM and Marsland, AL and Kang, C and McAuley, E and Ikonomovic, MD and Pascoal, TA and Villemagne, VL and Lopez, OL and Cohen, AD and Esteban-Cornejo, I and Yates, NA and Erickson, KI and Karikari, TK},
title = {Streamlined resource-efficient plasma amyloid-beta mass spectrometry assay has improved biomarker performance in preclinical Alzheimer's disease.},
journal = {Nature communications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41467-026-68372-w},
pmid = {41571708},
issn = {2041-1723},
support = {P30 AG066468/AG/NIA NIH HHS/United States ; P01 AG025204/AG/NIA NIH HHS/United States ; R01 AG083874/AG/NIA NIH HHS/United States ; },
abstract = {Plasma amyloid-β (Aβ) peptides, alone or in ratio with p-tau217, show strong potential as Alzheimer's disease biomarkers. While immunoprecipitation-mass spectrometry (IP-MS) is the preferred method for plasma Aβ quantification, current assays are resource- and time-intensive. Here, we developed a streamlined IP-MS method using a cost-effective instrument that significantly improved the efficiency of an original assay by incorporating a single immunoprecipitation step, an optimized buffer system, and approximately 75% reductions in antibody and sample volume requirements. Technical validation revealed excellent dilution linearity (r[2]>0.99), high precision (< 10% variation), enhanced sensitivity, improved Aβ recovery, and markedly increased signal-to-noise ratios. In a large cohort of cognitively normal older adults (n = 317), the plasma Aβ1-42/Aβ1-40 ratio achieved stronger concordance with Aβ-PET and superior accuracies to identify abnormal scans (AUC 0.81 vs. 0.65 for the original assay). Notably, accuracies remained high even with plasma volumes as low as 100 μL. The improved IP-MS method enables robust and simplified plasma Aβ assessment in Alzheimer's disease, with implications for prognosis, diagnosis and intervention trials.},
}

@article {pmid41571675,
year = {2026},
author = {Gaire, BP and Koronyo, Y and Vit, JP and Hutton, A and Subedi, L and Fuchs, DT and Swerdlow, N and Rentsendorj, A and Shahin, S and Martinon, D and Robinson, E and Ljubimov, AV and Schneider, JA and Schneider, LS and Hawes, D and Graham, SL and Gupta, VK and Mirzaei, M and Black, KL and Meyer, JG and Arditi, M and Crother, TR and Koronyo-Hamaoui, M},
title = {Identification of Chlamydia pneumoniae and NLRP3 inflammasome activation in Alzheimer's disease retina.},
journal = {Nature communications},
volume = {17},
number = {1},
pages = {771},
pmid = {41571675},
issn = {2041-1723},
mesh = {*Alzheimer Disease/microbiology/metabolism/pathology/immunology ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism/genetics ; Animals ; *Chlamydophila pneumoniae/immunology/isolation & purification ; *Inflammasomes/metabolism/immunology ; Amyloid beta-Peptides/metabolism ; *Retina/microbiology/pathology/metabolism/immunology ; Humans ; Mice ; Male ; Female ; Disease Models, Animal ; *Chlamydophila Infections/microbiology/immunology/pathology ; Mice, Transgenic ; Mice, Inbred C57BL ; Aged ; Interleukin-1beta/metabolism ; Microglia/metabolism ; Cognitive Dysfunction/microbiology ; Brain/pathology/metabolism ; Neurons/metabolism ; Peptide Fragments/metabolism ; },
abstract = {Chlamydia pneumoniae is an intracellular bacterium implicated in Alzheimer's disease (AD), but its role in retinal pathology and disease progression is unclear. Here we identify Chlamydia pneumoniae inclusions in the retina, showing higher burden in AD retina and brain, increasing with APOEε4, disease stage, and cognitive deficit. Retinal and cortical proteomics reveal bacterial-infection and related NLRP3-inflammasome pathways. Retinal NLRP3 is elevated in mild cognitive impairment and activated in AD dementia, evidenced by increased caspase-1, cleaved interleukin-1β, and cleaved N-terminal gasdermin-D. Chlamydia pneumoniae associates with amyloid-β42, inflammation, apoptosis, pyroptosis, and AD status. In neuronal cultures and APPSWE/PS1ΔE9 model mice, infection induces amyloid-β, inflammasome activation, neuroinflammation, and neurotoxicity, and chronic infection worsens cognition. Fewer pathogen-colocalized microglia are found in AD retinas, implying impaired clearance. Machine learning detects retinal Chlamydia pneumoniae or NLRP3, combined with amyloid-β42, as predictors of AD diagnosis and stage. These findings support a disease-amplifying role for Chlamydia pneumoniae and propose NLRP3-attenuation or antibiotic-based early interventions.},
}

*Alzheimer Disease/microbiology/metabolism/pathology/immunology
*NLR Family, Pyrin Domain-Containing 3 Protein/metabolism/genetics
Animals
*Chlamydophila pneumoniae/immunology/isolation & purification
*Inflammasomes/metabolism/immunology
Amyloid beta-Peptides/metabolism
*Retina/microbiology/pathology/metabolism/immunology
Humans
Mice
Male
Female
Disease Models, Animal
*Chlamydophila Infections/microbiology/immunology/pathology
Mice, Transgenic
Mice, Inbred C57BL
Aged
Interleukin-1beta/metabolism
Microglia/metabolism
Cognitive Dysfunction/microbiology
Brain/pathology/metabolism
Neurons/metabolism
Peptide Fragments/metabolism

@article {pmid41571600,
year = {2026},
author = {Yang, Y and Shi, Z and Zhang, Z and Sun, J and Gao, F},
title = {Engineering In Situ Activatable Integrated Polymer Dots with a Defined Chiral Microenvironment for In Vivo Enantioselective Monitoring of D-Noradrenaline in Brains with Alzheimer's Disease.},
journal = {Analytical chemistry},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.analchem.5c07059},
pmid = {41571600},
issn = {1520-6882},
abstract = {Enantioselective discrimination of enantiomers is very important to reveal the function and concentration fluctuation of chiral isomers in biological processes and disease pathogenesis. It remains challenging to distinguish D/L-enantiomers because they possess identical chemical composition and very similar physicochemical properties. Norepinephrine (NE) is a chiral monoamine neurotransmitter that shows extensive physiological effects on both the peripheral and central nervous systems of mammals and plays significant roles in the pathogenesis of Alzheimer's disease (AD). However, specific fluorescent probes for direct enantioselective discrimination of D/L-NE have rarely been reported so far, although gold standard methods such as chiral high-performance liquid chromatography (HPLC) and circular dichroism (CD) spectroscopy have been established. In this study, we present an integrated and in situ activatable chiral D-NE probe, BTTD polymer dots (Pdots) derived from a chiral fluorescent conjugated polymer, for distinguishing D-NE from L-NE based on the defined chiral microenvironment. BTTD Pdots exhibited high selectivity over other amino neurotransmitters, including dopamine and epinephrine, fast response within 2 s, good biocompatibility, and favorable penetrating efficiency of 37.02% across the blood-brain barrier (BBB). BTTD Pdots were successfully applied to fluorescence imaging of the NE exocytosis process induced by a high concentration of K[+], and also used to monitor D-NE levels in the brains of AD mice. The results reveal that the D-NE level is substantially lower in the brain with AD than in normal mice. This study provides a distinctive avenue for designing a chiral fluorescent probe for differentiating enantiomers through engineering a defined chiral microenvironment with clew-like polymer-derived Pdots.},
}

@article {pmid41571449,
year = {2026},
author = {Hu, N and Yang, X and Feng, F and Zhang, B and Liu, Y and Gao, H and Chen, Q and Zhang, CJ and Chen, X and Yan, F and Haller, S and Lui, S},
title = {Amyloid-related imaging abnormalities (ARIA) in Alzheimer's immunotherapy: a framework and challenges for global surveillance strategies.},
journal = {Journal of neurology, neurosurgery, and psychiatry},
volume = {},
number = {},
pages = {},
doi = {10.1136/jnnp-2025-337198},
pmid = {41571449},
issn = {1468-330X},
}

@article {pmid41571432,
year = {2026},
author = {Satoh, R and Ali, F and Dickson, DW and Lowe, VJ and Josephs, KA and Whitwell, JL},
title = {Subtracting First Principal Component May Improve 4R Tau Detectability on [[18]F]Flortaucipir Tau PET.},
journal = {Journal of nuclear medicine : official publication, Society of Nuclear Medicine},
volume = {},
number = {},
pages = {},
doi = {10.2967/jnumed.125.271019},
pmid = {41571432},
issn = {1535-5667},
abstract = {[[18]F]flortaucipir PET imaging has shown relatively low sensitivity for detecting four-repeat (4R) tau, which limits its utility in 4R tauopathies such as progressive supranuclear palsy (PSP). Previous studies have suggested that the first component of principal-component analysis includes non-disease-related uptake in non-Alzheimer tauopathies. In this study, we tested the hypothesis that subtracting this component could increase sensitivity to 4R tau using a large PSP cohort. Methods: Prospectively recruited patients with PSP (n = 141; 80 Richardson syndrome, 44 PSP-subcortical, and 17 PSP-cortical variants) and controls (n = 102) underwent [[18]F]flortaucipir PET. The first principal component (PC1) was extracted from the SUV ratio (SUVR) images of 62 controls and then subtracted from the remaining controls (n = 40) and all PSP patients. We compared the diagnostic performance before and after PC1 subtraction by evaluating SUVR differences between PSP and controls, as well as across PSP clinical variants, and by calculating correlation coefficients between SUVR and the severity of tau pathology. Results: Area under the receiver operating characteristic curves differentiating PSP and controls were improved by PC1 subtraction in the frontal white matter (0.54 to 0.67; P = 0.002) and subcortical (0.69 to 0.87; P < 0.001) regions. In the frontal regions, no differences were observed across PSP clinical variants before PC1 subtraction, whereas the PSP-cortical variant showed an SUVR higher than that of the PSP Richardson syndrome and PSP-subcortical variants after PC1 subtraction (adjusted P < 0.05). A correlation with the severity of tau pathology was observed only in the red nucleus before PC1 subtraction, whereas correlations were observed in the precentral, superior frontal gyrus, and red nucleus after PC1 subtraction (adjusted P < 0.05). Conclusion: Our approach enhanced the diagnostic performance of [[18]F]flortaucipir PET in PSP and increased sensitivity to 4R tau, suggesting that subtracting the first principal component improves the detectability of subtle 4R tau uptake and the potential utility of [[18]F]flortaucipir PET imaging for non-Alzheimer tauopathies.},
}

@article {pmid41571430,
year = {2026},
author = {Ngam, PI and Anzai, Y and Cliatt Brown, CJ and Frost, NA and Keown Sorweid, M and Thientunyakit, T and Minoshima, S and , },
title = {Copathologies of Limbic-Predominant Age-Related TDP-43 Encephalopathy and Alzheimer Disease: [[18]F]FDG PET Statistical Mapping and Quantitative MRI Volumetry.},
journal = {Journal of nuclear medicine : official publication, Society of Nuclear Medicine},
volume = {},
number = {},
pages = {},
doi = {10.2967/jnumed.125.270614},
pmid = {41571430},
issn = {1535-5667},
abstract = {Limbic-predominant age-related transactive response DNA-binding protein 43 kDa encephalopathy (LATE) is emerging as a prevalent neurodegenerative disorder in aging populations, mimicking the clinical presentation of Alzheimer disease (AD). This study investigates in vivo [[18]F]FDG PET and MRI biomarkers in detecting probable LATE neuropathologic change. Methods: We retrospectively analyzed 944 [[18]F]FDG PET cases referred from cognitive disorder clinics in a tertiary care center. To characterize the LATE and AD findings objectively and quantitatively, we created 3-dimensional stereotactic surface projection PET templates for LATE neuropathologic change (n = 6) and AD neuropathologic change (n = 32) from autopsy-confirmed Alzheimer's Disease Neuroimaging Initiative and University of Utah datasets, respectively. All 3-dimensional stereotactic surface projection z score [[18]F]FDG maps were created in comparison to normal PET scans from 20 control cases whose amyloid PET scans were negative. Using the autopsy-derived z score maps, z score product indices (the individual z score map multiplied by the z scores of autopsy-confirmed cohorts) were generated for each subject, stratifying participants into probable LATE, probable LATE and AD (LATE+AD), and probable AD. Clinical and quantitative MRI volumetry data were compared across the groups using 1-way or Welch ANOVA and Fisher exact tests, depending on the assessed variables. Results: Of the 944 clinical cases, 13.0% were characterized as probable LATE (2.4% pure LATE and 10.6% LATE+AD) and 23.7% were characterized as probable AD without LATE. MRI volumetry revealed that the medial temporal lobe was most affected in pure LATE cases (P < 0.001), whereas the orbitofrontal gyrus and lateral temporal lobe were most vulnerable in mixed LATE+AD cases (P = 0.001; P < 0.001). Post hoc analysis identified the entorhinal cortex and amygdala as key regions for distinguishing mixed LATE+AD cases from pure LATE and pure AD cases, respectively (P = 0.05; P < 0.001). Subgroup analysis of the probable LATE+AD group demonstrated additive or synergistic effects of both pathologies, with three quarters of cases exhibiting concordant lateralized metabolic brain changes, predominantly left-sided, based on LATE and AD z score products (P < 0.001). A similar pattern of left-dominant brain atrophy was observed in MRI volumetry. Conclusion: Substantial numbers of our patients exhibited LATE features that were characterized objectively using scans from autopsy-proven cases. These LATE cases were associated with specific regional atrophy measured by quantitative MRI. Cases with LATE+AD copathologies demonstrated synergistic hemispheric involvement. Further investigations of such synergistic changes between LATE and AD are warranted.},
}

@article {pmid41571406,
year = {2026},
author = {Franceschi, AM and Peng, S and Banegas, JI and Keir, G and Gordon, ML and Eidelberg, D and Ma, Y},
title = {Utility of [[18]F]PI-2620 as Universal Biomarker for the Amyloid/Tau/Neurodegeneration Classification of Alzheimer Disease: An Exploratory Study with Dual-Phase PET Imaging.},
journal = {AJNR. American journal of neuroradiology},
volume = {},
number = {},
pages = {},
doi = {10.3174/ajnr.A8980},
pmid = {41571406},
issn = {1936-959X},
abstract = {BACKGROUND AND PURPOSE: Our purpose was to identify spatial covariance patterns of dual-phase [[18]F]PI-2620 PET in biomarker-confirmed Alzheimer disease (AD) and healthy control subjects by applying data-driven multivariate analysis to multimodality neuroimaging data. We also tested the ability of pattern expression values in individual subjects to predict amyloid status and evaluate the efficacy of [[18]F]PI-2620 as a single, universal biomarker for the amyloid/tau/neurodegeneration (A/T/N) classification.

MATERIALS AND METHODS: Twenty-five subjects (15 men, 10 women, mean age: 64.5 ± 10.1, range 51-89) including 15 with amyloid-positive AD and 10 amyloid-negative healthy controls were analyzed. Brain PET images of dual-phase [[18]F]PI-2620 (early-phase for cerebral perfusion; late-phase for tau pathology) and late-phase [[18]F]florbetaben for amyloid pathology were acquired in each participant alongside high-resolution brain MRI. PET images were converted into maps of standard uptake value ratio by using cerebellar GM as reference region. Spatial covariance analysis was performed separately in the standard brain space by using a well-established computing toolbox in the public domain.

RESULTS: We identified distinct Alzheimer disease-related patterns (ADRP) of spatial covariance capturing prominent abnormal features in brain amyloid, tau, and perfusion (ADRP-amyloid, ADRP-tau, and ADRP-perfusion) underlying this disease. There was some overlap among these topographies particularly between ADRP-tau and ADRP-amyloid. ADRP expression scores of each pattern differentiated AD from healthy controls (P < .0001) with group discriminant analysis yielding an accuracy of 96% in predicting amyloid status with the combination of ADRP-tau and ADRP-perfusion scores. These scores correlated positively among themselves and with several clinical measures of disease severity in the combined subject group.

CONCLUSIONS: Analysis of AD and normal controls suggests a potential role of [[18]F]PI-2620 as a single biomarker for the A/T/N classification.},
}

@article {pmid41571385,
year = {2026},
author = {Zhu, L and Pan, Y and Wang, ZL},
title = {Graph-Theoretical Analysis of Resting-State EEG Networks Differentiates Alzheimer's Disease and Frontotemporal Dementia.},
journal = {The International journal of neuroscience},
volume = {},
number = {},
pages = {1-16},
doi = {10.1080/00207454.2026.2620704},
pmid = {41571385},
issn = {1563-5279},
abstract = {BACKGROUND: Alzheimer's disease (AD) and frontotemporal dementia (FTD) are neurodegenerative diseases with overlapping symptoms, complicating diagnosis. EEG-derived brain connectivity metrics, based on network neuroscience, can quantify brain network organization, but comparisons between AD and FTD using standardized EEG datasets are limited.

METHODS: We analyzed a publicly available EEG dataset consisting of 36 AD patients, 23 FTD patients, and 29 healthy controls (HC). Resting-state eyes-closed and eyes-open EEGs were analyzed across delta, theta, alpha, and beta bands. Phase-locking values (PLV) estimated functional connectivity between 19 electrodes, and graph-theory metrics were derived using the Brain Connectivity Toolbox. Group differences were assessed using ANOVAs with FDR correction, followed by Tukey tests.

RESULTS: AD patients showed reduced global efficiency and small-worldness, especially in the alpha and beta bands under eyes-closed conditions, indicating decreased integration. FTD patients exhibited localized network disruptions in frontal and central regions, particularly reduced node degree and local efficiency at F3/F4 and Pz electrodes, suggesting region-specific dysfunction. These differences were more prominent in the eyes-closed state.

CONCLUSION: EEG graph-theory analysis revealed distinct network alterations in AD and FTD. AD showed impaired global integration and loss of small-world architecture, while FTD demonstrated region-specific disruptions. These findings suggest that EEG graph metrics may serve as cost-effective biomarkers for differentiating dementia subtypes and understanding disease-specific network dysfunction.},
}

@article {pmid41571197,
year = {2026},
author = {Tan, CH and Tan, JJX},
title = {Not just anyone: Living situation is indirectly associated with cognitive impairment via depressive symptoms.},
journal = {Journal of affective disorders},
volume = {},
number = {},
pages = {121218},
doi = {10.1016/j.jad.2026.121218},
pmid = {41571197},
issn = {1573-2517},
abstract = {OBJECTIVES: Socially isolated individuals are at a greater risk of cognitive decline. We examined whether this relationship is dependent on the type of household living situation, living alone or living with others (spouse/partner or relative/friend), and the indirect effects of depression.

METHODS: We evaluated 10,545 cognitively normal (CN, mean age = 71.6) and 9334 individuals with mild cognitive impairment (MCI, mean age = 72.9) cross-sectional data from the National Alzheimer's Coordinating Center. Participants' living situation was classified as living alone, living with spouse/partner, or living with a relative/friend. Cognitive function and depression were assessed by a neuropsychological battery and the Geriatric Depression Scale respectively. Cross-sectional mediation was tested using regression-based path analyses.

RESULTS: In CN individuals, living with a spouse/partner was associated with higher cognitive performance compared to all other living situations, while living with a relative/friend was associated with the worst cognitive performance. This difference was most evident in females. MCI individuals living with a relative/friend also had lower cognitive performance even when compared to individuals living alone. Greater depressive symptoms among those living with a relative/friend mediated this difference, accounting for 7% and 10% of the effect in CN and MCI respectively.

DISCUSSION: Our findings suggest that living situations may entail social dynamics that elicit psychological stresses and impact cognitive aging. While living with a spouse/partner may provide cognitive resilience through social support, living alone may be more beneficial for cognitive preservation than living with a relative/friend due to lower depressive symptoms, particularly for CN females and individuals with MCI.},
}

@article {pmid41571168,
year = {2026},
author = {Malvandi, AM and Gerosa, L and Maroni, P and Orlando, ME and Mohammadipour, A and Lombardi, G},
title = {miRNA-206 in crosstalk muscle and central nervous system pathophysiology during exercise: a double-edged sword with therapeutic potential.},
journal = {Neuroscience and biobehavioral reviews},
volume = {},
number = {},
pages = {106569},
doi = {10.1016/j.neubiorev.2026.106569},
pmid = {41571168},
issn = {1873-7528},
abstract = {Physical activity triggers complex molecular responses in skeletal muscle, with increasing evidence showing systemic signaling roles for muscle-derived microRNAs (myomiRs). Among these, miR-206 has attracted attention for its dual function: promoting muscle regeneration but potentially harming the central nervous system (CNS). This review examines how miR-206 expression is regulated during exercise and its effects on muscle biology-such as fiber-type specification, mitochondrial changes, and neuromuscular junction (NMJ) repair. It also explores the paradoxical effects of high miR-206 levels in the CNS, where it targets brain-derived neurotrophic factor (BDNF), reducing neuroplasticity and increasing vulnerability to neuropsychiatric and neurodegenerative diseases. The review highlights disease-specific aspects, showing miR-206 as harmful in Alzheimer's, stroke, and depression, but potentially protective in amyotrophic lateral sclerosis (ALS). We discuss its potential as a biomarker and therapeutic target, stressing tissue-specific regulation approaches. Overall, miR-206 plays a key role in muscle-brain communication, with important implications for exercise, aging, and CNS disorders.},
}

@article {pmid41571080,
year = {2026},
author = {Yan, L and Wang, H and Shi, J and Tan, H and Liu, Q},
title = {Bibliometric analysis of neuroinflammation in Alzheimer's Disease: Insights from APP/PS1 mouse model research in the past two decades.},
journal = {Neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.neuroscience.2026.01.020},
pmid = {41571080},
issn = {1873-7544},
abstract = {BACKGROUND: The APP/PS1 transgenic mouse is a foundational model in Alzheimer's disease (AD) research, particularly for investigating the pivotal role of neuroinflammation in disease pathogenesis. Although substantial experimental work has explored inflammatory mechanisms in AD, the field still lacks a comprehensive overview of how research hotspots have evolved, which key scientific questions remain unresolved, and how global research efforts align with existing mechanistic gaps. Therefore, this investigation systematically evaluated scholarly trends, geographic contributions, institutional productivity, and thematic evolution to synthesize actionable insights that will guide subsequent experimental designs.

METHODS: Bibliometric analysis was conducted on peer-reviewed articles indexed in the Web of Science Core Collection (2005-2024). Analytical tools, including VOSviewer, CiteSpace, and Bibliometrix, were employed to quantify research output, collaborative networks, citation metrics, and keyword co-occurrence patterns.

RESULTS: Annual publication numbers exhibited exponential growth post-2015, reflecting an intensified focus on neuroinflammatory mechanisms in AD. China and the United States contributed 83.4 % of total publications, with the University of Barcelona as the most productive institution. High-impact journals such as Nature, Nature Neuroscience, and Brain Behavior Immunity. The analysis identified key scientific issues and evolving research fronts, with current hot topics focusing on oxidative stress, activated microglia releasing inflammatory cytokines, and abnormal autophagy-lysosome pathways.

CONCLUSION: The APP/PS1 mice have a significantly enhanced mechanistic understanding of neuroimmune interactions in AD pathogenesis. Future research should explore microglia-mediated neuroinflammation and brain-gut microbiome interactions to uncover novel diagnostic and therapeutic strategies for AD. This study offers an evidence-based framework to guide researchers using APP/PS1 mice model.},
}

@article {pmid41571079,
year = {2026},
author = {Qiao, J and Zhou, G and Wu, S and Shang, H and Yuan, Q and Sun, J},
title = {A multi-view DTI feature fusion framework for enhanced diagnosis of Alzheimer's disease.},
journal = {Neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.neuroscience.2026.01.024},
pmid = {41571079},
issn = {1873-7544},
abstract = {Alzheimer's disease (AD) is an irreversible neurodegenerative disorder. Diffusion tensor imaging (DTI) is widely used to detect brain alterations for diagnosis, but most methods rely on single-scale information. Therefore, this study proposes the multi-view feature learning framework incorporating residual block-based 3D convolutional neural network (3D-CNN) for AD diagnosis. First, tract-based spatial statistics were applied to extract voxel-based features from fractional anisotropy (FA) and mean diffusivity (MD) maps. Second, the residual block-based 3D-CNN model was employed to extract high-level deep features, enhancing model ability to capture global contextual information. Third, fiber tracking was used to construct structural connectivity networks, which served as connectivity-based features. Fourth, radiomics was applied to extract texture and shape features from FA and MD images. These four types of features were linearly combined and subsequently reduced in dimensionality using the ReliefF algorithm. Finally, an ensemble learning strategy was employed to perform three binary classification tasks among the AD, mild cognitive impairment (MCI), and normal control (NC) groups. Additionally, layer-wise relevance propagation (LRP) was utilized to improve the interpretability of the 3D-CNN model. Evaluated on 427 subjects from the Alzheimer's Disease Neuroimaging Initiative database, the framework integrates complementary multi-scale information, achieving superior performance. For the AD vs. NC classification, it attained an accuracy of 97.6%, a sensitivity of 98.0%, and an area under the curve of 0.964, outperforming several state-of-the-art methods. These results demonstrate that our approach enhances diagnostic accuracy and contributes to understanding disease mechanisms by identifying multi-scale biomarkers associated with known AD pathology.},
}

@article {pmid41571077,
year = {2026},
author = {Abdel-Aal, RA and Meligy, FY and Kamel, G and Ashry, IEM},
title = {Cognitive Enhancing Effect of Canagliflozin in Aluminum-Induced Rat Model of Alzheimer's-Like Disease: Cross Talk Between Amyloid-Β and BDNF/GSK-3β Signaling.},
journal = {European journal of pharmacology},
volume = {},
number = {},
pages = {178581},
doi = {10.1016/j.ejphar.2026.178581},
pmid = {41571077},
issn = {1879-0712},
abstract = {The strong relationship between Alzheimer's Disease (AD) and diabetes mellitus (DM) is described by the term "type 3 diabetes". Canagliflozin (CAN), a sodium-glucose co-transporter 2 inhibitor (SGLT2i), is an antidiabetic agent under investigation as a potential new treatment for AD due to its acetylcholinesterase (AChE) inhibitory properties. We aimed to examine the effect of CAN on the efficacy of the anti-acetylcholinesterase, rivastigmine (RIV), against aluminum chloride (AlCl3)-induced AD rat model. The efficacy of CAN, RIV, and CAN plus RIV against abnormal behavioral, biochemical, and histological changes in AlCl3-induced AD in rats was examined. Three weeks of treatment with CAN partially reversed the AlCl3-induced behavioral dysfunction, along with significantly elevated levels of brain-derived neurotrophic factor (BDNF) and decreased levels of AChE, glycogen synthase kinase-3β (GSK3β), amyloid beta (Aβ) deposits, and inducible nitric oxide synthase (iNOS) expression. Histological examination revealed that CAN administration significantly increased RIV's efficacy by protecting neurons in rats' hippocampal tissues from AlCl3-induced damage. Interestingly, the RIV+CAN combination exhibited a more pronounced inhibitory effect on Aβ plaque formation, iNOS activity, and neurodegeneration compared to either RIV or CAN alone. However, this combination did not show any additive benefits for behavior, AChE activity, BDNF, or GSK3β concentrations compared with RIV alone. Our research indicates that CAN has potential benefits for AD, as evidenced by improvements in cognitive abilities, cholinergic activity, and neurogenesis in rats with AD. This is attributed to the upregulation of BDNF/GSK3β signaling, reduced neuroinflammation, and Aβ deposition.},
}

@article {pmid41570992,
year = {2026},
author = {Salvo, MA and Cuddy, LK and Prokopenko, D and Watkins, E and Tanzi, RE and Vassar, R},
title = {Alzheimer's disease-linked ACE variants increase ACE1 catalytic activity and production of angiotensin II.},
journal = {The Journal of biological chemistry},
volume = {},
number = {},
pages = {111171},
doi = {10.1016/j.jbc.2026.111171},
pmid = {41570992},
issn = {1083-351X},
abstract = {Angiotensin-converting enzyme (ACE) is a validated risk locus for developing late-onset Alzheimer's disease (AD). Although ACE1 expression and enzyme activity correlate with AD diagnosis, the mechanism by which this occurs is unclear. As a cell membrane-bound and shed peptidase, ACE1 is most commonly known to produce angiotensin II (Ang II), which has been linked to AD pathogenesis, but also has been shown to cleave toxic Aβ42 to Aβ40, further complicating its role in AD. Previous work from our group characterized a rare ACE coding variant discovered through whole-genome and whole-exome sequencing of late-onset AD families: ACE rs4980 (R1279Q mutation) increases neuronal ACE1 and subsequent signaling through the central renin-angiotensin system (RAS), inducing age-associated hippocampal neurodegeneration. In this work, we report on two additional ACE variants associated with increased risk for developing AD: rs3730043 (T916M) and rs142947404 (N1036K). These variants were selected to investigate their effect on ACE1 protein processing and function in SH-SY5Y stable cell lines. In these cell lines, ACE1 protein trafficking to the cell surface was unaltered. Interestingly, however, both T916M and N1036K mutant cell lines resulted in increased ACE1 catalytic activity. Consequently, both mutant cell lines produced elevated levels of Ang II, a known mediator of neurodegeneration. This study provides further evidence for the role of ACE1 in AD and warrants continued research on this topic.},
}