@article {pmid41765956,
year = {2026},
author = {Škorvagová, A and Ribaldi, F and Cerman, J and Wang, C and Scheffler, M and Mendes, AJ and Wyss-Dominguez, C and Garibotto, V and Frisoni, G and Andel, R and Boccalini, C and Hort, J},
title = {Hypoperfusion in early-phase amyloid PET as a predictor of cognitive decline in Alzheimer's disease.},
journal = {European journal of nuclear medicine and molecular imaging},
volume = {},
number = {},
pages = {},
pmid = {41765956},
issn = {1619-7089},
}

@article {pmid41765871,
year = {2026},
author = {Xu, J and Zhang, X and Cui, Y and Zheng, Q and Wang, C and Kang, Y and Xing, L and Zhang, X and Qin, Y and Yuan, K and Huang, L and Tian, J},
title = {Decoding the educational impact on Alzheimer's risk: an umbrella review of Mendelian randomization evidence.},
journal = {Aging & mental health},
volume = {},
number = {},
pages = {1-13},
doi = {10.1080/13607863.2026.2632752},
pmid = {41765871},
issn = {1364-6915},
abstract = {OBJECTIVES: Alzheimer's disease (AD) remains a major global health challenge. The objective of this umbrella review is to synthesize Mendelian Randomization (MR) evidence evaluating the causal relationship between educational attainment (EA) and AD risk, thereby addressing the inherent limitations of observational studies.

METHODS: We conducted a comprehensive literature search in PubMed, Embase, and Web of Science up to July 6, 2023. MR studies investigating the causal relationship between EA and AD risk were included. We assessed study quality using the STROBE-MR checklist and graded evidence strength. Due to heterogeneity in genetic instruments, a qualitative synthesis was performed.

RESULTS: Eleven publications examining 41 distinct associations were included. Most studies reported a consistent protective effect of EA on AD risk. However, this protective effect was attenuated when mediated by cognitive traits, which independently protected against AD. Quality assessment revealed variability in adherence to reporting guidelines, notably concerning study pre-registration and broad generalizability.

CONCLUSION: Findings highlight a complex interplay between EA, cognitive traits, and AD risk, aligning with the cognitive reserve hypothesis. Ultimately, EA exhibits a protective effect against AD, largely mediated by cognitive traits, and likely explained by multiple structural and lifestyle mechanisms. Future research must prioritize longitudinal designs and gene-environment interactions.},
}

@article {pmid41765696,
year = {2026},
author = {Huang, H and Sharoar, MG and Pathoulas, J and Fan, L and He, W and Xiang, R and Yan, R},
title = {Corrigendum to "Accumulation of neutral lipids in dystrophic neurites surrounding amyloid plaques in Alzheimer's disease" [2024 Apr;1870(4):167086.].},
journal = {Biochimica et biophysica acta. Molecular basis of disease},
volume = {},
number = {},
pages = {168201},
doi = {10.1016/j.bbadis.2026.168201},
pmid = {41765696},
issn = {1879-260X},
}

@article {pmid41765633,
year = {2026},
author = {Wu, F and Wang, D and Tabang, DN and Liu, PK and Wang, Z and Liu, Y and Steenhagen, A and Puglielli, L and Li, L},
title = {High-throughput simultaneous quantification of glycopeptides and phosphopeptides enabled by 12-plex DiLeu isobaric tags and dual-functional Titanium(IV)-IMAC material.},
journal = {Analytica chimica acta},
volume = {1395},
number = {},
pages = {345231},
doi = {10.1016/j.aca.2026.345231},
pmid = {41765633},
issn = {1873-4324},
abstract = {BACKGROUND: Protein glycosylation and phosphorylation are critical post-translational modifications (PTMs) that regulate diverse physiological and pathological processes, yet their comprehensive characterization remains challenging due to low abundance and poor ionization efficiency. Recent advances using epoxy-ATP-Ti[4+]-IMAC materials have enabled simultaneous enrichment of N-glycopeptides, phosphopeptides, and mannose-6-phosphate glycopeptides. However, high-throughput, multiplexed quantification of these PTMs is still lacking. This work addresses the need for an efficient strategy capable of simultaneously enriching, identifying, and quantitatively comparing glycosylation and phosphorylation across multiple biological samples.

RESULTS: We developed a high-throughput workflow integrating epoxy-Ti[4+]-IMAC enrichment with custom N,N-dimethyl leucine (DiLeu) isobaric tags to achieve 12-plex quantitative analysis of N-glycosylation and phosphorylation for the first time. This streamlined one-tube sample preparation protocol enabled robust, simultaneous enrichment and quantification of PTMs from complex mouse brain samples. Application to APP/PS1 transgenic mice versus wild-type controls produced quantitative identification of 1975 N-glycopeptides and 1181 phosphopeptides. Comparative profiling revealed substantial PTM alterations associated with Alzheimer's disease (AD)-related pathology. Differentially modified proteins mapped to key biological pathways, including synapse organization, synaptic membrane regulation, and cell adhesion. The abundance patterns highlighted broad disruptions in PTM-mediated signaling and provided molecular insights into synaptic dysfunction in the APP/PS1 model.

SIGNIFICANCE AND NOVELTY: This integrated DiLeu isobaric labeling-epoxy-Ti[4+]-IMAC platform provides a powerful, high-throughput solution for the simultaneous quantification of glycosylation and phosphorylation, enabling detailed investigation of PTM interplay. By uncovering disease-associated modifications in AD mouse models, this method offers new opportunities to identify mechanistic biomarkers and therapeutic targets. Its versatility and scalability make it broadly applicable to PTM-centric studies across diverse biological systems, including biofluids, cell lysates and tissues.},
}

@article {pmid41765432,
year = {2026},
author = {Miwa, H},
title = {[Identifying common neural circuit dysfunctions across psychiatric disorders through neurophysiological indices].},
journal = {Nihon yakurigaku zasshi. Folia pharmacologica Japonica},
volume = {161},
number = {2},
pages = {70-74},
doi = {10.1254/fpj.25069},
pmid = {41765432},
issn = {0015-5691},
abstract = {The etiology of psychiatric disorders such as schizophrenia, autism spectrum disorder (ASD), and depression remains largely unknown, and to date, no clear diagnostic criteria or curative pharmacological treatments have been established. One contributing factor is that patients with psychiatric disorders actually represent a heterogeneous population, yet are treated as a single group in clinical trials, which lowers the success rate of drug development. Against this background, there has been growing advocacy for stratification based on objective biomarkers, such as those proposed in the Research Domain Criteria (RDoC), rather than relying solely on syndrome-based classifications such as the DSM-5 or ICD-11 for diagnosis and therapeutic development. Furthermore, the elucidation of psychiatric pathophysiology and the development of effective pharmacological and therapeutic interventions require common objective indices that can bridge human and animal studies to enable translational research between preclinical and clinical domains. In patients with schizophrenia, sleep disturbances are consistently observed with high reproducibility, and abnormalities in sleep spindle generation during non-REM sleep have recently attracted attention as a novel biomarker. Moreover, spindle abnormalities have also been reported not only in schizophrenia but in subsets of patients with Alzheimer's disease, ASD, and Parkinson's disease, suggesting the possibility of shared pathophysiological mechanisms across distinct psychiatric and neurological disorders. In this article, I highlight electroencephalographic markers such as non-REM sleep spindles and gamma oscillations-objective neurophysiological indices measurable in both humans and experimental animals-that may deepen our understanding of the pathophysiology of psychiatric disorders and ultimately contribute to the development of novel therapeutics.},
}

@article {pmid41765417,
year = {2026},
author = {Son, S and Kim, S and Jeon, MT and Choi, M and Kim, KS and Lee, S and Nah, SY and Kim, DG},
title = {Amyloid-β aggregates induce vasculopathy via ferroptosis in brain endothelial cells.},
journal = {Brain pathology (Zurich, Switzerland)},
volume = {},
number = {},
pages = {e70074},
doi = {10.1111/bpa.70074},
pmid = {41765417},
issn = {1750-3639},
support = {2021R1C1C1011427//National Research Foundation of Korea/ ; RS-2024-00508681//National Research Foundation of Korea/ ; GLT-25071-100//National Research Foundation of Korea/ ; 25-BR-02-03//Korea Brain Research Institute/ ; 25-BR-08-01//Korea Brain Research Institute/ ; RS-2023-KH135534//Korea Dementia Research Center/ ; RS-2023-KH-138465//Korea Dementia Research Center/ ; },
abstract = {Amyloid-β (Aβ) plaque is the defining pathological feature of Alzheimer's disease (AD) and a target of various therapeutic agents for affected patients. Recent studies have demonstrated the dysfunction of the blood-brain barrier (BBB) in AD; however, how Aβ plaque induces BBB dysfunction, particularly in brain endothelial cells (ECs), remains elusive. This study investigates the lipid peroxidation-mediated ferroptosis pathway induced by Aβ via conducting RNA sequencing, phosphorylation analysis, metabolite analysis, western blotting, and immunofluorescent staining both in vitro and in vivo. Here, we demonstrate that Aβ is associated with lipid metabolic pathways following Aβ exposure in brain ECs. Additionally, Aβ aggregates induce the formation and accumulation of peroxidized lipid droplets. Lastly, Aβ is significantly reduced in brain ECs and 5xFAD mice by the inhibition of the lipid metabolic pathway associated with lipid peroxidation and ROS formation. Our findings from in vitro and in vivo both suggest that Aβ plays a causative role in the process of lipid peroxidation and might provide a potential target for the development of therapeutic interventions for AD.},
}

@article {pmid41765195,
year = {2026},
author = {Gojani, EG and Farzin, H and Sutherland, RJ and Mohajerani, MH},
title = {Serotonergic Psychedelics as Epigenetic Modulators: A Paradigm Shift in Alzheimer's Disease Therapeutics.},
journal = {Neuroscience and biobehavioral reviews},
volume = {},
number = {},
pages = {106619},
doi = {10.1016/j.neubiorev.2026.106619},
pmid = {41765195},
issn = {1873-7528},
abstract = {Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder characterized by amyloid-β (Aβ) accumulation, tau pathology, synaptic dysfunction, and neuroinflammation, which collectively drive progressive memory loss, cognitive decline, and behavioral changes. Increasing evidence implicates epigenetic dysregulation as a key contributor to these pathological processes by altering gene expression programs. Serotonergic psychedelics, which primarily act as agonists of the serotonin 2A receptor (5-HT2AR), have recently attracted attention for their ability to robustly promote neuroplasticity and induce sustained transcriptional changes in the brain. Preclinical studies indicate that these compounds can modulate epigenetic mechanisms, including histone modifications and DNA methylation (DNAm). This review examines the emerging intersection between psychedelic-induced epigenetic modulation and AD pathology, and proposes that targeted engagement of 5-HT2Ars may help counteract epigenetic abnormalities that contribute to AD pathogenesis.},
}

@article {pmid41764697,
year = {2026},
author = {Reddy, CS and Kandy, AT and Sivakumar, G and Vijayakumar, A},
title = {Exploring molecular frameworks for modulating NLRP3-driven neuroinflammation in Alzheimer's disease.},
journal = {Molecular diversity},
volume = {},
number = {},
pages = {},
pmid = {41764697},
issn = {1573-501X},
support = {202223-UGCES-22-GE-TAM-F SJSGC-792//University Grants Commission/ ; },
}

@article {pmid41764603,
year = {2026},
author = {Dar, SA and Imtiaz, N and Dar, RA},
title = {Early Diagnosis of Alzheimer's: Machine Learning Analysis Leveraging Structural MRI.},
journal = {Current Alzheimer research},
volume = {},
number = {},
pages = {},
doi = {10.2174/0115672050421991260125153049},
pmid = {41764603},
issn = {1875-5828},
abstract = {INTRODUCTION: Alzheimer's disease (AD) is characterized by significant brain atrophy, detectable via structural MRI. There has been less focus on cortical degeneration in subcortical regional deterioration-particularly during the transition from Mild Cognitive Impairment (MCI) to AD-which remains underexplored. This study aims to identify subcortical regions with progressive atrophy using surface-based morphometry (SBM) and evaluate their potential for early AD diagnosis.

METHODS: This longitudinal study collected data from MCI patients (6 months) who later progressed to Alzheimer's within 3 years, alongside healthy controls followed across four time points (6 months-3 years). Reported in line with STARD guidelines, the study aimed to evaluate model performance in distinguishing progressive MCI-to-AD from healthy controls to advance early Alzheimer's diagnosis. The study leveraged the ADNI dataset to analyse 68 subcortical regions in MCI-to-AD converters (MCI-AD) and Healthy Controls (HC) over 6 months to 3 years (i.e., at 6 months, 1 year, 2 years, and 3 years). The groups were classified beforehand using the Clinical Dementia Rating and the Mini-Mental Status Examination scores. Accordingly, three surfacebased morphometry (SBM) metrics-cortical thickness (CTh), gyrification index (GI), and sulcal depth (SD)-were evaluated in the progressive MCI group (individuals with MCI who later converted to Alzheimer's disease) as well as in healthy controls, to quantify morphological changes. Finally, the morphological data were utilized to train and test machine learning models for classification and prediction.

RESULTS: Cortical regions exhibiting significant atrophy were identified using paired-samples ttests between 6 months and 3 years. In parallel, machine learning (ML) models were trained and tested on the same dataset to differentiate progressive MCI-to-AD cases from healthy controls across multiple time points (6 months, 1 year, 2 years, and 3 years), and subsequently to predict the progression to Alzheimer's disease. Certain evaluation metrics were considered for the classifier performance, i.e., Accuracy, F1-score, and AUC-ROC.

DISCUSSION: Sub-cortical SBM metrics, particularly CTh, are sensitive to early AD-related atrophy, offering potential biomarkers for disease progression. ML models trained on these features enable accurate classification, with performance peaking near diagnosis-highlighting their utility in early intervention.

CONCLUSION: SBM-derived subcortical atrophy patterns aid early AD detection and, when combined with ML, offer a scalable predictive framework. Among metrics, CTh showed the greatest decline in MCI-AD, followed by SD and GI. Progressive deterioration was observed in specific subcortical regions, accelerating near diagnosis. Classifiers achieved higher accuracy in distinguishing MCI-AD from HC at later time points, highlighting stage-specific shifts in feature importance.},
}

@article {pmid41764587,
year = {2026},
author = {Titeca, J and Scarioni, M and Oyaert, M and Van Langenhove, T},
title = {Automated high-throughput quantification of plasma p-tau217 and APOE-ε4 for Alzheimer's disease diagnosis and cognitive decline in a memory cohort.},
journal = {Alzheimer's research & therapy},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13195-026-01996-8},
pmid = {41764587},
issn = {1758-9193},
abstract = {BACKGROUND: Blood-based biomarkers could improve the precision of Alzheimer's disease (AD) clinical diagnosis and expand access to targeted treatments. Therefore, we evaluated the diagnostic accuracy of plasma Elecsys p-tau217 (Roche) and compared it with Elecsys p-tau181 (Roche) and Lumipulse p-tau217 (Fujirebio). We also assessed the added value of APOE-ε4 carrier status, plasma Aβ42 and Aβ42/40 in a memory-clinic cohort and evaluated associations with longitudinal cognition.

MATERIALS AND METHODS: A total of 187 patients from the Cognitive Centre Ghent University (CCUG) biobank, classified as AD (n = 103) or non-AD cognitive disorders (n = 84) based on CSF biomarkers (CSF Aβ42/40 ratio, total tau and p-tau181), were included. Plasma Elecsys p-tau181, p-tau217, and APOE-ε4 were measured on the Roche cobas[®] pro e801, and p-tau217, Aβ42, and Aβ40 on the Fujirebio LUMIPULSE G1200. ROC analyses and single- and two-cut-off strategies (95% sensitivity/specificity) were applied. Subgroup analyses examined APOE-ε4 status, renal function, cerebral amyloid angiopathy (CAA) features, Fazekas score, and longitudinal cognition.

RESULTS: Elecsys plasma p-tau217 showed high discriminative performance for AD versus non-AD (AUC 0.939), comparable to Lumipulse p-tau217 (AUC 0.950; p = 0.485). Elecsys p-tau181 performed lower than Elecsys p-tau217 (AUC 0.903; p = 0.043). Using a two-cut-off strategy, the intermediate proportion was 19.9% for Elecsys p-tau217, 11.9% for Lumipulse p-tau217, and 33.2% for Elecsys p-tau181. Adding APOE-ε4 to Elecsys p-tau217 improved discriminative performance (AUC 0.970, p = 0.02) and reduced intermediates to 11.0%. Adjustment for Aβ42 on the Fujirebio platform did not significantly increase the AUC (0.950 vs. 0.957; p = 0.322) and modestly reduced intermediate classifications (11.9% to 10.0%). Higher baseline Elecsys p-tau217 was associated with lower baseline MoCA and a trend towards faster MoCA decline (p = 0.07). Age, sex, renal function, Fazekas score, and CAA were not significantly associated with Elecsys p-tau217 concentrations.

CONCLUSION: Plasma Elecsys p-tau217 measured on an automated high-throughput platform shows excellent diagnostic accuracy for AD. Incorporating APOE-ε4 further improves classification, while Aβ42 adjustment had only limited additional impact. Baseline p-tau217 also reflects cognitive severity and may relate to subsequent cognitive decline in the memory-clinic setting.},
}

@article {pmid41764185,
year = {2026},
author = {Fang, C and Ai, J and Wang, Q and Xu, B and Zhang, J and Zhang, ZM},
title = {Asymmetric synthesis of Heteroatom-bridged [3.2.1]Octane scaffolds via enantioselective β-H elimination reaction.},
journal = {Nature communications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41467-026-69960-6},
pmid = {41764185},
issn = {2041-1723},
support = {22031004//National Natural Science Foundation of China (National Science Foundation of China)/ ; 22501294//National Natural Science Foundation of China (National Science Foundation of China)/ ; 20212308//Shanghai Municipal Education Commission/ ; 23ZR1445600//Science and Technology Commission of Shanghai Municipality (Shanghai Municipal Science and Technology Commission)/ ; },
abstract = {N-bridged [3.2.1]octanes (tropanes) and their related bridged bicyclic systems constitute highly sought-after scaffolds in drug discovery and development. Notably, the enantioselective synthesis of chiral 3-aryltropanes which are compounds widely distributed across bioactive pharmaceutical agents remains underdeveloped. Tropinone is a readily available and cost-effective starting material. By initiating the synthesis from tropinone, it is possible to substantially lower the synthesis costs. Here we describe an enantioselective Pd/Ming-Phos-catalyzed β-H elimination reaction of Tropinone-derived N-arylsulfonylhydrazones and aryl bromides to give chiral tropanes and oxatropanes. Strikingly, this study achieves enantioselective β-H elimination which needs to simultaneously control over both diastereoselectivity during the migratory insertion and enantioselectivity during the β-H elimination. This approach shows broad functional group tolerance, good enantiocontrol as well as easy scale-up. Moreover, the synthetic value is further demonstrated by the enantioselective catalytic total synthesis of drugs for treating Alzheimer's disease and monoamine transporter ligands. Additionally, both the facile elaborations and the preliminary biological activities of the products demonstrate the application potential.},
}

@article {pmid41763632,
year = {2026},
author = {Zheng, M and Su, W and Tian, L and Gao, W},
title = {The glymphatic system as a brain scavenger in Alzheimer's disease: mechanisms and therapeutic implications.},
journal = {Brain research},
volume = {},
number = {},
pages = {150221},
doi = {10.1016/j.brainres.2026.150221},
pmid = {41763632},
issn = {1872-6240},
abstract = {Alzheimer's disease (AD), the most common neurodegenerative disorder worldwide, is increasingly recognized as a major threat to global health. Its pathogenesis remains highly complex, and effective treatments are still lacking. Recent research, however, has identified a crucial player in this process-the glymphatic system, which acts as a metabolic "scavenger" in the brain, responsible for clearing waste products such as amyloid-β (Aβ) and hyperphosphorylated tau protein. Impairment of this system leads to the accumulation of these toxic proteins, which are hallmark pathological features of AD. This review comprehensively examines how glymphatic dysfunction contributes to the aggregation of Aβ and tau, thereby driving AD progression. Astrocytes regulate fluid transport via aquaporin-4 (AQP4) water channels, while microglia modulate glymphatic efficiency through phagocytosis and neuroinflammatory signaling. These cells work in concert to maintain brain homeostasis. However, in AD, the loss of polarized AQP4 expression in astrocytes, obstruction of cerebrospinal-interstitial fluid exchange by Aβ and tau, and dysregulated microglial activation collectively accelerate disease pathology. Advances in diagnostic biomarkers-such as Aβ/tau PET imaging and CSF profiles of GFAP/sTREM2-offer promising avenues for early AD detection. Meanwhile, therapeutic strategies targeting glymphatic-astrocyte-microglia interactions, including AQP4 enhancers, TREM2 agonists, and anti-inflammatory agents, open new possibilities for treatment. By integrating insights from preclinical and clinical studies, this review underscores the vital role of the glymphatic system in early intervention, highlighting potential approaches to slow AD progression through enhanced waste clearance and immunomodulation.},
}

@article {pmid41763564,
year = {2026},
author = {Ge, J and Ge, J and Bao, M and Zhang, L and Li, K and Ji, A and Mao, X and Jiang, X and Yue, K and Sun, J and Luo, P},
title = {Epidemiological trends and cross-country inequalities in the global burden of Alzheimer's disease and other dementias in postmenopausal women from 1990 to 2021.},
journal = {Ageing research reviews},
volume = {},
number = {},
pages = {103069},
doi = {10.1016/j.arr.2026.103069},
pmid = {41763564},
issn = {1872-9649},
abstract = {OBJECTIVE: To evaluate the trends, cross-country inequalities, and risk factors associated with Alzheimer's disease and other dementias (ADOD) in postmenopausal women globally, and project the disease burden to 2050.

METHODS: The age-standardized rates (ASRs) and 95% uncertainty intervals (UIs) of prevalence, incidence, mortality, and disability-adjusted life-years (DALYs) for ADOD among postmenopausal women were estimated by using the Global Burden of Disease, Injuries, and Risk Factors Study (GBD) 2021 data. The average annual percentage change (AAPC) was calculated using joinpoint regression. A decomposition analysis was performed to quantify the contributions of population growth, aging, and epidemiologic changes. The slope index of inequality (SII) and concentration index, as recommended by the World Health Organization, were used to evaluate the cross-country inequalities in ADOD burden. The ADOD burden among postmenopausal women to 2050 was projected using the Bayesian age-period-cohort analysis (BAPC) model. Risk factor attribution was quantified according to GBD methodology.

RESULTS: In 2021, the estimated global ASRs of prevalence, incidence, mortality, and DALYs of ADOD among postmenopausal women were 4414.52 (95%UIs: 3492.78, 5504.77), 751.18 (95%UIs: 517.67, 1019.3), 164.29 (95%UIs: 41.79, 425.37), and 2935.7 (95%UIs: 1349.85, 6306.48) per 100000 population, respectively. East Asia recorded the highest total number of cases and the highest ASRs of prevalence and incidence, while Central Sub-Saharan Africa showed the highest ASRs of mortality and DALYs. From 1990-2021, the ADOD burden increased most rapidly during 2019-2021. Population growth (82.07% contribution) and aging (12.48%) were the primary drivers of increases in global DALYs. SDI-related inequalities escalated over time, with the SII increasing from 1275.06 [95% confidence interval (CI): 1037.55, 1512.57] in 1990 to 1697.71 (95%CI: 1430.70, 1964.73) in 2021. The BAPC model showed that both the ASRs and case number of prevalence, incidence, mortality, and DALYs were predicted to increase from 2022 to 2050, with predicted ASRs of 6067.51 [95% credible interval (CrI): 2149.42, 9985.60], 1052.37 (95%CrI: 361.2, 1743.54), 186.15 (95%CrI: 90.01, 282.3), and 3602.34 (95%CrI: 1530.01, 5674.67) per 100,000 population in 2050. High fasting plasma glucose was identified as the leading risk factor contributing to ADOD burden.

CONCLUSIONS: From 1990 to 2021, there was an overall upward trend in the global burden of ADOD among postmenopausal women. Driven by demographic shifts (population growth and aging) and metabolic risks (particularly high fasting plasma glucose), the burden of postmenopausal women with ADOD is expected to increase substantially. Postmenopausal women in higher SDI countries bore a disproportionately higher ADOD burden, and the SDI-related inequalities among countries widened during the study period. These findings highlight major challenges in the prevention, control, and management of ADOD in postmenopausal women. Health authorities should shift from reactive treatments to proactive prevention, emphasizing the establishment of targeted health policies, glucose control, and optimizing medical resource allocation to meet the heterogeneous needs of this vulnerable population.},
}

@article {pmid41763443,
year = {2026},
author = {Zafarjonovna, AZ and Aysulu, E and Matlyuba, S and Rashid, H and Azamatovich, JB and Ahmadjon, A and Barno, A and Kurbanovna, AM and Ugli, MRM and Shaxodat, I and Rustam, T and Jumaniyazovna, MG and Ishankulov, A},
title = {Small extracellular vesicles as emerging biomarkers and therapeutic targets in neurodegenerative diseases.},
journal = {Clinica chimica acta; international journal of clinical chemistry},
volume = {},
number = {},
pages = {120932},
doi = {10.1016/j.cca.2026.120932},
pmid = {41763443},
issn = {1873-3492},
abstract = {Small extracellular vesicles (sEVs) have rapidly emerged as versatile mediators of intercellular communication with significant potential to transform the diagnosis and treatment of neurodegenerative diseases (NDDs). Increasing evidence shows that sEVs not only participate in the propagation of pathogenic proteins but also serve as accessible, CNS-informative carriers of molecular signatures that reflect neuronal, glial, and systemic disease processes. This dual role positions sEVs at the intersection of biomarker discovery and therapeutic innovation. In the diagnostic domain, advances in immunoaffinity capture, single-vesicle analysis, and multi-omics profiling have enabled increasingly precise characterization of neuron-, astrocyte-, and microglia-derived sEVs, revealing candidate markers for Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and related disorders. However, translation remains limited by methodological heterogeneity, a lack of large-scale validation, and the need for standardized pre-analytical and analytical pipelines aligned with the ISEV/MISEV guidelines. On the therapeutic front, native and engineered sEVs, particularly those derived from mesenchymal and neural stem cells, demonstrate promising neuroprotective effects, including the modulation of neuroinflammation; the enhancement of synaptic resilience; and the delivery of antioxidant, anti-amyloid, or gene-modifying cargo across the blood-brain barrier. Scalable GMP manufacturing, cargo-loading strategies, targeting specificity, and long-term safety remain key challenges for clinical translation. This narrative review synthesizes current advances in sEV-based biomarkers and therapeutics, outlines technological and regulatory barriers, and proposes a translational roadmap spanning mechanistic discovery, platform standardization, and integration into precision-medicine frameworks. Collectively, emerging data position sEVs as powerful tools capable of reshaping the diagnostic and therapeutic landscape of NDDs, provided that coordinated multidisciplinary efforts address the remaining gaps in validation, scalability, and regulatory readiness.},
}

@article {pmid41763435,
year = {2026},
author = {Wang, C and Guan, Y and Chen, J and Liu, S and Li, H and Wang, S and Zhang, Y and Li, Y and Liu, Y and Li, L and Wang, D},
title = {PANoptosis inhibition by Morchella sextelata polysaccharide mediates neuroprotection in Alzheimer's disease models.},
journal = {International journal of biological macromolecules},
volume = {},
number = {},
pages = {151128},
doi = {10.1016/j.ijbiomac.2026.151128},
pmid = {41763435},
issn = {1879-0003},
abstract = {PANoptosis has been hypothesized to play a role in the pathogenesis of Alzheimer's disease (AD), with potential contributions to neuronal dysfunction and loss. This study aims to analyze the structural characteristics of Morchella sextelata polysaccharide (MSP) and to investigate its neuroprotective properties and the pathways implicated in AD pathology. The main chain of the MSP polysaccharide, with a molecular weight of 2283.3 kDa, consists of →4)-α-D-Glcp-(1 → and →4,6)-β-D-Glcp-(1 → linkages, and α-D-Glcp-(1 → connected as a branched chain to the O-4 position of →4,6)-β-D-Glcp-(1→. In behavioral tests, MSP enhances memory and cognitive function in mice, and it inhibits the production of Aβ in the mouse brain. Furthermore, proteomic and metabolomic analyses indicate that MSP may exert inhibitory effects on PANoptosis. Evidence shows that MSP suppresses pyroptosis induced by the NLRP3 inflammasome, apoptosis mediated by the caspase protein family, and necroptosis dependent on RIPK1. Overall, administration of MSP leads to significant improvements in memory and attenuation of brain pathology in APP/PS1 mice, effects that are attributed to its inhibition of PANoptosis.},
}

@article {pmid41763367,
year = {2026},
author = {Cheng, M and Zhu, D and Chen, S and Jia, J and Xu, J and Zeng, X},
title = {The therapeutic potential of cytisine and its derivatives in disorders of the central nervous system.},
journal = {Biochemical pharmacology},
volume = {},
number = {},
pages = {117853},
doi = {10.1016/j.bcp.2026.117853},
pmid = {41763367},
issn = {1873-2968},
abstract = {Cytisine is a quinolizidine alkaloid that is widely used in smoking cessation, exerting its neurological and other biological actions primarily through binding to the nicotinic acetylcholine receptor (nAChR). Cytisine binds to the nAChR (herein represented by α4β2) and exhibits distinct receptor recognition characteristics that provide a basis for the structural optimization of its derivatives in terms of affinity and selectivity. An increasing number of studies indicate that cytisine and its derivatives exhibit a variety of neuroprotective and functional benefits in disorders of the central nervous system (CNS), including Alzheimer's disease (AD), Parkinson's disease (PD), epilepsy, depression, and ischemic stroke. In this review, the binding interactions between cytisine and nAChR are discussed extensively. Then the neuroprotective roles of cytisine and its derivatives in CNS diseases are summarized, and cellular and molecular mechanisms are further highlighted. This review aims to provide a basis for further research and to promote the possible clinical application of cytisine and its derivatives. Taken together, cytisine and its derivatives may provide promising drug candidates to treat a range of CNS diseases.},
}

@article {pmid41763274,
year = {2026},
author = {Oriquat, G and Ali, AM and Patel, PN and Hanumanthayya, M and Priyadarshini-Nayak, P and Bainsal, N and Urazbaeva, D and Djumaniyazova, M and Ghahari, AA},
title = {Modulating Glymphatic Clearance in Alzheimer's Disease: Molecular Mechanisms, Imaging Biomarkers, and Emerging Interventions.},
journal = {Behavioural brain research},
volume = {},
number = {},
pages = {116138},
doi = {10.1016/j.bbr.2026.116138},
pmid = {41763274},
issn = {1872-7549},
abstract = {The glymphatic system supports cerebrospinal fluid (CSF) and interstitial fluid (ISF) exchange and helps clear neurotoxic proteins, including amyloid beta (Aβ) and tau. Evidence from experimental models and human observational studies links glymphatic dysfunction to Alzheimer's disease (AD), although causality in humans remains incompletely established. This review synthesizes advances in mechanisms, biomarkers, and interventions. Loss of aquaporin 4 (AQP4) polarization at astrocytic endfeet is consistently associated with reduced CSF-ISF exchange and greater Aβ and tau burden. Additional contributors, including meningeal lymphatic impairment, blood-brain barrier disruption, altered vascular pulsatility, sleep fragmentation, and perivascular structural remodeling, likely interact during early pathology. Clinically, surrogate measures such as perivascular space (PVS) enlargement and diffusion tensor-based indices including the Analysis along the perivascular space (ALPS) index provide indirect readouts of perivascular fluid behavior but are limited by intersite variability and incomplete specificity. Contrast enhanced MRI approaches can probe clearance more directly, yet they remain invasive and difficult to scale for routine use. Fluid biomarkers, including CSF AQP4 and related transport proteins, are promising but require robust analytical validation in large multicenter cohorts. Therapeutic directions include sleep and circadian optimization, vascular risk control and aerobic exercise, neuromodulation such as gamma frequency sensory stimulation, and molecular strategies targeting AQP4 anchoring, with careful attention to safety and feasibility. Standardized biomarkers and prospective longitudinal interventional trials are needed to test whether improving clearance proxies yields durable biomarker shifts and clinically meaningful benefits in AD.},
}

@article {pmid41763101,
year = {2026},
author = {Haut, MW and Teixeira, CVL and Worhunsky, PD and Mehta, RI and Malone, JE and Ward, M and Keith, CM and Phelps, HE and Pockl, S and Rajabalee, N and Sharif, K and Marano, G and D'Haese, PF and Rezai, AR},
title = {Memory Consolidation and ARIA in Individuals Receiving Anti-amyloid Monoclonal Antibodies.},
journal = {The journal of prevention of Alzheimer's disease},
volume = {13},
number = {5},
pages = {100519},
doi = {10.1016/j.tjpad.2026.100519},
pmid = {41763101},
issn = {2426-0266},
abstract = {Amyloid related imaging abnormalities (ARIA) are the most significant risk associated with the use of anti-amyloid monoclonal antibodies (MAB) for Alzheimer's disease (AD). Currently, the presence of the APOE ε4 allele is the best predictor for the development of ARIA. However, the degree of baseline memory impairment has not been fully explored as a risk factor for ARIA. Here, we examined MAB outcomes in a memory clinic population and compared patients with AD who developed ARIA to a case-matched group who did not develop ARIA. Participants who developed ARIA had greater numbers of recall intrusions and false positives, both markers for memory consolidation, at baseline than those who did not develop ARIA. We also observed greater baseline hippocampal and supplementary motor cortical atrophy with ARIA. These differences remained when controlling for the APOE ε4 allele and the presence of pretreatment microhemorrhages. Further investigation of memory impairment and associated brain atrophy is warranted to understand ARIA risk and MAB outcomes in AD.},
}

@article {pmid41763100,
year = {2026},
author = {Li, Q and Huang, L and Wang, Y and Guan, Y and Xie, F and Guo, Q},
title = {Visuospatial memory deficit, plasma p-tau217, and Aβ42/Aβ40 ratio enhance sensitivity to identify Aβ PET positivity in individuals with SCD.},
journal = {The journal of prevention of Alzheimer's disease},
volume = {13},
number = {5},
pages = {100525},
doi = {10.1016/j.tjpad.2026.100525},
pmid = {41763100},
issn = {2426-0266},
abstract = {INTRODUCTION: We hypothesize that specific cognitive assessments and plasma biomarkers may exhibit heightened sensitivity during the stage of subjective cognitive decline (SCD). The integration of these plasma biomarkers and cognitive assessments could enhance the ability to predict beta-amyloid (Aβ) pathology in individuals with SCD.

METHODS: A total of 231 participants, including 74 normal controls (NC) and 157 SCD, underwent Aβ and tau PET scans and blood testing for Aβ40, Aβ42, p-tau181, p-tau217, NfL, and GFAP. Cognitive assessments, plasma biomarkers, tau PET SUVr, and demographics were compared between Aβ+ and Aβ- groups within NC and SCD. The least absolute shrinkage and selection operator (LASSO) and logistic regression were employed to perform variable selection and develop predictive models.

RESULTS: We observed significantly worse global cognition, visuospatial memory performance, executive function, and metamemory, as well as higher tau PET SUVr, elevated levels of p-tau217, p-tau181, and GFAP, and lower Aβ42/Aβ40 ratios in SCD Aβ+ compared to SCD Aβ-. The model incorporating BVMT-LD and p-tau217 achieved a slightly higher AUC than the model using p-tau217 and Aβ42/Aβ40 (0.94 vs. 0.93). Partial correlation analyses indicated that both auditory verbal memory (AVLT-LD) and visuospatial memory (BVMT-LD) were significantly negatively associated with p-tau217, whereas only AVLT-LD demonstrated a significant negative association with tau pathology severity.

CONCLUSION: Visuospatial memory deficit and plasma p-tau217 are powerful biomarkers for identifying Aβ+ in SCD. Auditory verbal memory links to tau pathology severity, while visuospatial memory is more sensitive to Aβ deposition, supporting early intervention to prevent AD progression.},
}

@article {pmid41763076,
year = {2026},
author = {Ganesan, VK},
title = {Unusual expression of peripheral blood Alzheimer's markers, inflammatory cytokines, and cholinergic biomarkers in chronic kidney disease patients with cognitive dysfunction: Therapeutic impact of recombinant human erythropoietin (rHuEPO).},
journal = {Current research in translational medicine},
volume = {74},
number = {1},
pages = {103568},
doi = {10.1016/j.retram.2026.103568},
pmid = {41763076},
issn = {2452-3186},
abstract = {BACKGROUND: Patients with chronic kidney disease (CKD) are at a significantly increased risk of developing Alzheimer's disease (AD) and cognitive dysfunction compared to the general population. While recombinant human erythropoietin (rHuEPO) is commonly used to treat anemia in CKD, emerging evidence indicates that it also possesses neuroprotective properties. This study aimed to evaluate the therapeutic impact of rHuEPO on platelet expression of amyloid precursor protein (APP) proteolytic fragments, apolipoprotein E (ApoE), glycogen synthase kinase 3β (GSK3β), total Tau, and phosphorylated Tau species (P-Tau181, P-Tau217, and P-Tau231), along with plasma levels of APP cleaving enzymes, P-Tau217, P-Tau231, inflammatory cytokines, and cholinergic markers in CKD patients with cognitive dysfunction.

METHODS: A total of 60 CKD patients were enrolled, including 30 without cognitive dysfunction and 30 with cognitive dysfunction, as determined by neuropsychological assessment. Platelet protein expression levels of total Tau, P-Tau181, P-Tau217, P-Tau231, and ApoE were analyzed using Western blotting. Gene expression levels of APP-cleaving enzymes, ApoE, GSK3β, and MAPT in platelets were assessed by RT-PCR. Plasma concentrations of APP-cleaving enzymes, inflammatory cytokines, cholinergic markers, P Tau217, and P-Tau231 were quantified. Results were compared with healthy controls, normocytic normochromic anemia, and AD.

RESULTS: CKD patients with cognitive dysfunction showed significant alterations in the expression of platelet proteins (total Tau, P-Tau181, P Tau217, P-Tau231, and ApoE) and related genes (APP cleaving enzymes, ApoE, GSK3β, and MAPT), resembling the molecular profile observed in AD. Additionally, plasma levels of APP cleaving enzymes, inflammatory cytokines, cholinergic markers, and phosphorylated Tau species (P-Tau217 and P-Tau231) were significantly altered in these patients. Notably, after 6 months of rHuEPO therapy, these biomarkers showed marked improvement in CKD patients with cognitive dysfunction.

CONCLUSION: These findings suggest that rHuEPO may offer therapeutic benefits beyond anemia correction, potentially serving as a supportive treatment for cognitive dysfunction in CKD by modulating AD-related peripheral biomarkers.},
}

@article {pmid41763014,
year = {2026},
author = {Xie, S and Liang, Y and Yang, T and Sheng, D and Ding, L and Jia, J and , },
title = {Diagnostic and prognostic utility of serum β-synuclein in Alzheimer's disease: a longitudinal cohort study.},
journal = {The journal of prevention of Alzheimer's disease},
volume = {13},
number = {4},
pages = {100514},
doi = {10.1016/j.tjpad.2026.100514},
pmid = {41763014},
issn = {2426-0266},
abstract = {BACKGROUND: Serum β-synuclein is an emerging blood-based biomarker for synaptic integrity in Alzheimer's disease (AD). However, its comparative performance against the established CSF marker neurogranin and its prognostic utility for longitudinal disease progression remain to be fully characterized.

METHOD: We analyzed 475 participants from the Alzheimer's Disease Neuroimaging Initiative. We compared serum β-synuclein and CSF neurogranin using receiver operating characteristic analysis and Cox proportional hazards models. We also assessed the cross-sectional associations of both biomarkers with cognitive and neuroimaging markers using linear regression. Linear mixed-effects models were applied to determine if baseline serum β-synuclein levels and longitudinal rate of change predicted disease progression. Finally, the trajectory of serum β-synuclein was modeled across the AD continuum.

RESULTS: Serum β-synuclein distinguished clinical AD dementia from controls with high accuracy (AUC = 0.84). Cross-sectionally, it exhibited robust associations with cognitive deficits and neuroimaging markers, comparable to or exceeding those of CSF neurogranin. Higher baseline serum β-synuclein, but not CSF neurogranin, significantly predicted the risk of conversion to dementia (hazard ratio = 1.83). Longitudinally, both elevated baseline levels and faster rates of increase in serum β-synuclein predicted accelerated cognitive decline and neurodegeneration, independent of baseline amyloid or tau pathology. Trajectory analysis revealed that serum β-synuclein levels accelerated significantly over time specifically in individuals with concurrent amyloid and tau pathology.

DISCUSSION: Serum β-synuclein serves as a robust prognostic biomarker for AD, demonstrating diagnostic accuracy for clinical dementia and superior predictive utility for disease conversion compared to CSF neurogranin. Its ability to track synaptic degeneration independent of core proteinopathies highlights its potential as a dynamic outcome measure for monitoring disease progression in clinical trials.},
}

@article {pmid41763013,
year = {2026},
author = {Choo, IH and Park, H and Gordon, BA and Bateman, RJ and , },
title = {Longitudinal subcortical volume changes and their correlations with multiple PET and fluid biomarkers in dominantly inherited Alzheimer's disease.},
journal = {The journal of prevention of Alzheimer's disease},
volume = {13},
number = {4},
pages = {100513},
doi = {10.1016/j.tjpad.2026.100513},
pmid = {41763013},
issn = {2426-0266},
abstract = {BACKGROUND: Alzheimer's disease postmortem studies demonstrate that amyloid plaques and neurofibrillary tangles are present in subcortical regions.

OBJECTIVE: To investigate longitudinal subcortical structural changes in autosomal dominant Alzheimer's disease in relation to multiple PET and fluid biomarkers.

DESIGN: Dominantly Inherited Alzheimer's Network (DIAN) Observational study SETTING: Multicenter study PARTICIPANTS: Participants were identified as mutation-carriers of pathologic variants in presenilin-1, presenilin-2, or amyloid precursor protein and as non-carriers from the same families as the mutation-carriers. They underwent baseline and 2 and more times longitudinal follow-up assessments of multiple biomarkers MEASUREMENTS: Participants underwent structural MRI, ¹¹C-Pittsburgh Compound B PET, ¹⁸F-fluorodeoxyglucose PET, and CSF and plasma assessments. Rates of biomarker change as a function of estimated years to symptom onset were estimated using multivariate linear mixed-effects models, and longitudinal associations between subcortical atrophy and multiple biomarkers were evaluated.

RESULTS: A total of 601 participants completed one or more clinical evaluations, with up to eight annual visits. Mutation carriers showed significantly greater longitudinal atrophy in the left amygdala, bilateral thalamus, putamen, nucleus accumbens, and hippocampus compared with non-carriers (Bonferroni-corrected p < 0.05). The earliest divergence was observed 13.2 years before the expected symptom onset in the right nucleus accumbens, following amyloid-β (Aβ) accumulation in the right thalamus that began 23.8 years before onset. Among carriers, atrophy in the right thalamus, bilateral putamen, and bilateral nucleus accumbens was significantly associated with region-specific or cortical Aβ accumulation, as well as with CSF Aβ42, Aβ42/Aβ40 ratio, total tau, and phosphorylated tau (Bonferroni-corrected p < 0.05).

CONCLUSIONS: The present findings may provide a unique and well-characterized model for investigating the temporal ordering of Alzheimer's disease biomarkers.},
}

@article {pmid41763010,
year = {2026},
author = {Jimenez-Maggiora, GA},
title = {Remote outcome measures in Alzheimer's disease clinical trials: A call to action.},
journal = {The journal of prevention of Alzheimer's disease},
volume = {13},
number = {4},
pages = {100528},
doi = {10.1016/j.tjpad.2026.100528},
pmid = {41763010},
issn = {2426-0266},
}

@article {pmid41763009,
year = {2026},
author = {Sun, D and Yu, L and Liao, C and Xu, Y and Liu, W and Wang, X},
title = {Healthy lifestyle and Alzheimer's disease in individuals with hyperlipidemia: A prospective cohort study.},
journal = {The journal of prevention of Alzheimer's disease},
volume = {13},
number = {4},
pages = {100520},
doi = {10.1016/j.tjpad.2026.100520},
pmid = {41763009},
issn = {2426-0266},
abstract = {BACKGROUND: Whether healthy lifestyle behaviors are associated with Alzheimer's disease (AD) risk among individuals with hyperlipidemia remains unclear.

METHODS: We analyzed 241,642 dementia-free participants from the UK Biobank. A weighted lifestyle score (0-7) was derived from seven factors and categorized into five tiers. Hyperlipidemia was defined as lipid-lowering medication use or LDL-cholesterol ≥ 4.0 mmol/L. Cox regression estimated hazard ratios (HRs) and 95% confidence intervals (CIs).

RESULTS: Over a median follow-up of 14.5 years, 1728 AD cases occurred, including 977 cases among 104,082 individuals with hyperlipidemia. Compared with the intermediate tier, unhealthy lifestyle was associated with elevated AD risk (HR: 1.17; 95% CI: 1.02-1.35), while healtshy and very healthy tiers were associated with progressively lower risk (HR=0.85 and 0.74, respectively). These associations were evident among individuals with hyperlipidemia, but not statistically significant among those without hyperlipidemia.

CONCLUSIONS: Healthy lifestyle patterns were associated with lower AD risk among individuals with hyperlipidemia, with greater risk reductions observed for healthier lifestyle tiers.},
}

@article {pmid41763008,
year = {2026},
author = {Budak, M and Heffernan, KS and Paruzel, V and Moallemian, S and Fausto, BA and Ashton, N and Zetterberg, H and Elahi, FM and Gluck, MA},
title = {Vascular stiffness predicts plasma markers of neurodegeneration among older African Americans.},
journal = {The journal of prevention of Alzheimer's disease},
volume = {13},
number = {4},
pages = {100523},
doi = {10.1016/j.tjpad.2026.100523},
pmid = {41763008},
issn = {2426-0266},
abstract = {BACKGROUND: Vascular health is a critical and potentially modifiable determinant of Alzheimer's disease (AD) risk, yet its contribution to early neurodegenerative processes remains incompletely understood, particularly among African Americans, who experience a disproportionate AD burden. Estimated pulse wave velocity (ePWV), derived from age and blood pressure, provides a scalable index of vascular stiffness.

OBJECTIVES: To examine associations between vascular stiffness and plasma biomarkers of AD-related neurodegeneration in older African Americans.

DESIGN: Cross-sectional observational study.

SETTING: Community-based aging cohort study conducted at an academic research center.

PARTICIPANTS: A total of 145 cognitively unimpaired older African Americans (mean age=71.18±6.83 years; 110 women).

MEASUREMENTS: ePWV was calculated using validated equations based on age and blood pressure. Plasma biomarkers included phosphorylated tau217 (p-tau217; N=145), phosphorylated tau231 (p-tau231; N=126), glial fibrillary acidic protein (GFAP; N=126), neurofilament light chain (NfL; N=126), and amyloid-β42/40 ratio (Aβ42/40; N=126). Multivariable regression models adjusted for sex, education, pulse pressure, waist-to-hip ratio, global cognition, and hypertension status.

RESULTS: Higher ePWV was significantly associated with higher plasma concentrations of p-tau217 (β=0.34, p=.006), GFAP (β=0.55, p<.001), and NfL (β=0.52, p<.001), but not with p-tau231 and Aβ42/40 (p>.05).

CONCLUSIONS: Greater vascular stiffness, indexed by elevated ePWV, was associated with circulating markers of tau-related neurodegeneration, astrocytic activation, and axonal injury in cognitively unimpaired older African Americans. The absence of association with p-tau231 and Aβ42/40 suggests preferential effects on neurovascular damage and later tau-related processes, but no primary effect on biomarkers related to Aβ pathology, still highlighting vascular health as a modifiable target for AD prevention.},
}

@article {pmid41762988,
year = {2026},
author = {Dongye, C and Wang, S and Chen, X and Li, C and Zhao, Y and Chan, TD and Boukherroub, R and Chen, X},
title = {Skin toxicity of liquid crystal monomers (LCMs): Mitochondrial dysfunction and metabolic dysregulation revealed by integrated multi-omics analysis.},
journal = {Ecotoxicology and environmental safety},
volume = {312},
number = {},
pages = {119953},
doi = {10.1016/j.ecoenv.2026.119953},
pmid = {41762988},
issn = {1090-2414},
abstract = {Liquid crystal monomers (LCMs), as core components of liquid crystal displays (LCDs), are emerging as environmental materials due to their widespread use and potential for human and ecological exposure. Even as inquiries pertaining to the environmental and health risks of LCMs are progressing, their direct toxic effects on human organs and ecosystems persist in being inadequately comprehended. The present research underscores the hazards entailed by prolonged LCMs exposure, with specific reference to skin cells and animal models, under daily exposure magnitudes. This study reveals that long-term LCMs exposure disrupts mitochondrial function in skin cells, triggers inflammatory pathways (TNF signaling), and downregulates critical proteins (PLOD2, DDIT4) and metabolites (ATP, glutathione), indicating oxidative stress and cellular dysfunction. In vivo experiments further demonstrate histopathological damage in mouse skin, including disordered skin appendages and adipose disorganization, highlighting LCMs' hazardous potential. Multi-omics analysis links LCMs exposure to diseases such as lung cancer and Alzheimer's, while untargeted metabolomics identifies β-alanylleucine downregulation as a promising biomarker for LCM-induced toxicity. Given LCD e-waste growth, improper disposal releases LCMs, risking ecosystem bioaccumulation. These findings underscore the need for stricter regulation of LCMs throughout their lifecycle-from production to waste management-to mitigate ecological and health risks, with β-alanylleucine serving as a potential monitoring tool for environmental contamination.},
}

@article {pmid41762939,
year = {2026},
author = {Decaix, T and Dumurgier, J and Bouaziz-Amar, E and Cognat, E and Götze, K and Mouton-Liger, F and Hugon, J and Vrillon, A and Paquet, C and Lilamand, M},
title = {Assessment of medication-related risks for mortality prediction in Alzheimer's disease.},
journal = {Maturitas},
volume = {208},
number = {},
pages = {108896},
doi = {10.1016/j.maturitas.2026.108896},
pmid = {41762939},
issn = {1873-4111},
abstract = {BACKGROUND: In Alzheimer's disease, exposure to medications with anticholinergic or cognitive adverse effects may contribute to excess mortality, but direct comparisons between measures of this drug-related risk remain scarce.

METHODS: We retrospectively included from a memory clinic 440 patients aged ≥65 years with Alzheimer's disease confirmed by cerebrospinal fluid biomarkers (A + T+). Medication exposure was characterized in relation to polypharmacy and potentially inappropriate medications related to cognition (PIMCog, according to the Beers criteria), both treated as binary variables, and participants' anticholinergic burden (none, low-moderate or high) as rated by three scales (the ACB, ADS, and ARS). Mortality was ascertained until December 2024. Models were adjusted for demographic, clinical, and biomarker variables.

RESULTS: The mean age was 74.1 ± 5.8 years, and 58.2% were women. Polypharmacy was present in 42.5% and PIMCog in 32.3%. High anticholinergic burden was found in 21.0% of patients using ACB, 8.6% using ADS, and 6.8% using ARS. During a mean follow-up of 7.3 years, 225 patients (51.1%) died. In adjusted models, mortality was associated with the number of drugs [hazard ratio (HR) 1.06, 95% confidence interval (CI) 1.01-1.11], continuous PIMCog (HR 1.21, 95% CI 1.02-1.45), high ACB (HR 1.45, 95% CI 1.01-2.11), and high ADS (HR 2.00, 95% CI 1.23-3.26), but not ARS. Antidepressants were the most frequent drugs recorded on each scale, representing 38.9% (ACB), 41.2% (ADS), and 56.1% (ARS), as well as PIMCog (33.8%). Substantial overlap was observed, with 98 patients identified by all four scales.

CONCLUSION: ACB and ADS scores and PIMCog were more strongly associated with mortality than polypharmacy. These findings highlight the combined effect of clinical factors and support systematic medication review targeting anticholinergic drugs in cognitively vulnerable patients.},
}

@article {pmid41762754,
year = {2026},
author = {Santos, LTR and Coelho Filho, JM and Lôbo, RR and Peixoto Junior, AA and Macedo, DS},
title = {Response to the letter by Yang and Xia: Clarifying the clinical and methodological boundaries of plasma and salivary p-Tau181 in Alzheimer's disease.},
journal = {Journal of the neurological sciences},
volume = {483},
number = {},
pages = {125833},
doi = {10.1016/j.jns.2026.125833},
pmid = {41762754},
issn = {1878-5883},
}

@article {pmid41762696,
year = {2026},
author = {Song, D},
title = {Decoding Naturalistic Episodic Memory with Artificial Intelligence and Brain-Machine Interface.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {},
number = {},
pages = {e20125},
doi = {10.1002/advs.202520125},
pmid = {41762696},
issn = {2198-3844},
support = {N66001-14-C-4016//Defense Advanced Research Projects Agency (DARPA) Restoring Active Memory (RAM) program/ ; RF1DA055665/1R01EB031680//NIH/NIDA BRAIN Initiative - Theories, Models and Methods (TMM) program/ ; HR0011-25-3-0142//DARPA Investigating how Neurological Systems Process Information in REality (INSPIRE) program/ ; },
abstract = {Episodic memory integrates what, where, and when of experience into a coherent autobiographical narrative. Decades of research have identified hippocampal place, time, and concept cells as neural correlates of these components. Yet a major challenge remains: real-life memory encoding occurs in high-dimensional, naturalistic settings, where multimodal sensory, emotional, and cognitive processes intertwine across time and context. Traditional paradigms and analytical tools are insufficient to decode the neural activity underlying such complex experiences. Recent advances in artificial intelligence (AI) offer new means to address this challenge. AI models, such as variational autoencoders and multimodal alignment frameworks, can extract latent representations from neural and behavioral data, capturing the naturalistic structure of memory encoding. Large language models further provide powerful frameworks for interpreting subjective memory reports, linking verbal narratives to memory encoding. When integrated with closed-loop brain-machine interfaces (BMIs) capable of recording from and manipulating large populations of neurons in relevant brain regions, these tools make it possible to address the long-standing questions: how to decode memory codes during naturalistic behaviors and whether these memory codes causally generate memories rather than merely correlate with them. This integrated AI-BMI framework outlines a roadmap from mapping to engineering memory, with implications for Alzheimer's disease, traumatic brain injury, and PTSD.},
}

@article {pmid41762606,
year = {2026},
author = {Patwekar, F and Patwekar, M and Wei, LS and Sharma, R and Varghese, R and Mohammed, A},
title = {Antibody-based nanoparticles in Alzheimer's disease: Innovations in diagnosis and therapy.},
journal = {Pathology, research and practice},
volume = {281},
number = {},
pages = {156421},
doi = {10.1016/j.prp.2026.156421},
pmid = {41762606},
issn = {1618-0631},
abstract = {BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by accumulation of amyloid-β (Aβ) plaque, tangles of tau neurofibres, chronic neuroinflammation, and dysfunction of the blood brain barrier (BBB). Monoclonal antibodies targeting Aβ and tau have focused disease-modifying potential, but their clinical impact is limited in brain penetration, immunogenicity, amyloid-related imaging abnormalities (ARIA), high treatment costs, and the need for repeated intravenous administration. These limitations has lead to discover in antibody-based nanoparticle platforms as advanced delivery and diagnosis.

OBJECTIVE: This review aims to evaluate antibody-based nanoparticles as emerging tools for the diagnosis and treatment of AD, focusing on nanoparticle design, antibody conjugation strategies, mechanisms of BBB transport, immune modulation, and current translational challenges.

CURRENT EVIDENCE: Recent preclinical studies reflects that antibody-functionalized nanoparticles can improve target specificity, enhance BBB transport by receptor-mediated and adsorptive transcytosis, and modulate neuroinflammatory responses by microglial Fc-receptor engagement. Advances in nanoparticle materials including gold, magnetic iron oxide, polymeric, and lipid-based systems has applications in both therapy and molecular imaging using MRI and PET. Critical barriers including nanoparticle instability, immune clearance, antibody denaturation after conjugation, long-term toxicity, manufacturing scalability, and regulatory uncertainty for hybrid biologic nanomaterial products exist.

CONCLUSION: Antibody-based nanoparticles represent promising but still evolving platform for precision diagnostics and targeted therapy in AD. While preclinical evidence is encouraging, successful clinical translation depends on standardized manufacturing, comprehensive safety evaluation, and well-designed trials. Future efforts focus on theranostic systems, multi-target antibody platforms addressing pathology, and regulatory frameworks supporting scalable and reproducible nanoparticle-based interventions.},
}

@article {pmid41762531,
year = {2026},
author = {Sanagi, T and Okumura, M and Lin, Y and Kanemura, S and Moon, E and Heo, Y and Takahara, K and Lee, YH and Tsunematsu, T},
title = {Amyloid fibrils in Alzheimer's disease differently modulate sleep and cortical oscillations in mice depending on the type of amyloid.},
journal = {Biophysical chemistry},
volume = {333},
number = {},
pages = {107599},
doi = {10.1016/j.bpc.2026.107599},
pmid = {41762531},
issn = {1873-4200},
abstract = {Alzheimer's disease (AD) is characterized by aggregation and deposition of the amyloid-beta (Aβ) protein in patients' brains, with aging contributing through oxidative stress and neuroinflammation. Sleep disturbances are common in patients with AD and exacerbate cognitive impairment. However, it remains unclear how aggregation of specific Aβ species in distinct brain regions contributes to sleep dysfunction. To address this, we characterized amyloid fibrils formed by Aβ1-40 (Aβ40) and Aβ1-42 (Aβ42) by assessing their structural and surface properties using fluorescence, CD, and NMR spectroscopy. Their morphology was also visualized using TEM and AFM. These analyses revealed that Aβ42 aggregates faster than Aβ40 and forms amyloid fibrils with distinct structural, surface, and morphological properties. To investigate their effects in vivo, we bilaterally injected Aβ40 and Aβ42 fibrils into the hippocampus of wild-type mice and recorded the electroencephalogram and electromyogram under freely moving conditions. Aβ42 amyloid fibrils significantly disrupted sleep architecture, particularly REM sleep, and altered oscillations, accompanied by neuronal loss. In contrast, Aβ40 amyloid fibrils mainly affected cortical activity with minimal neuronal loss and caused comparatively modest changes in sleep. These findings demonstrate that a single administration of Aβ amyloid fibril is sufficient to alter sleep/wakefulness state and cortical oscillations. The observed effects differ depending on the type of Aβ administered, suggesting that the physicochemical properties of the fibrils are closely linked to their capacity to induce sleep impairment. These findings shed light on AD-associated sleep disorders, which are differentially affected by the distinct properties of Aβ40 and Aβ42 aggregates.},
}

@article {pmid41762523,
year = {2026},
author = {Zhu, Y and Xiao, X and Liu, Y and Wang, Z and Luo, T and Xu, T and Yang, Q and Hao, X and Zhang, C and Zhang, S and Luo, S and Zhou, Y and Liao, X and Tian, Y and Weng, L and Fang, L and Tang, B and Jiao, B and Li, J and Shen, L},
title = {Short tandem repeat expansions in patients with neurodegenerative dementia.},
journal = {EBioMedicine},
volume = {125},
number = {},
pages = {106190},
doi = {10.1016/j.ebiom.2026.106190},
pmid = {41762523},
issn = {2352-3964},
abstract = {BACKGROUND: Due to the overlapping clinical features of neurodegenerative dementia (NDD)-including Alzheimer's disease (AD), frontotemporal dementia (FTD), dementia with Lewy bodies (DLB), and progressive supranuclear palsy (PSP), accurate diagnosis remains challenging in early stages. Multiple dementias can be caused by short tandem repeat (STR) expansions. However, systematic investigation of known pathogenic STRs in large dementia cohorts remains lacking.

METHODS: We used ExpansionHunter (EH) to assess 22 neurodegenerative disease-associated STRs in whole-genome sequencing (WGS) data from 950 patients with AD, 222 patients with FTD, 165 patients with DLB, 231 patients with PSP, and 1522 cognitively normal controls. Repeat primed-polymerase chain reaction (RP-PCR) was performed to validate EH calls that exceeded the intermediate thresholds of STR. We also attempted to use ExpansionHunter Denovo (EHDn) to detect C9orf72 expansions missed by EH.

FINDINGS: EHDn improved the detection rate of C9orf72 expansions. After sample quality control, 33 PCR-validated pathogenic expansions were identified in nine genes (C9orf72, ATXN8OS, NOTCH2NLC, HTT, FMR1, DMPK, AR, CACNA1A, and PPP2R2B) among 1559 patients with NDD, accounting for 2.12% of cases. Burden-based logistic regression analyses demonstrated that the presence of pathogenic STR expansions was significantly associated with NDD status (OR = 3.57, p = 4.70 × 10[-2]). Additionally, intermediate-length TBP alleles showed a nominal enrichment in PSP compared with controls (2.61% vs 0.54%; OR = 6.25, p = 2.00 × 10[-2]).

INTERPRETATION: Our findings provide evidence for the clinical pleiotropy of STRs in NDD and their involvement in NDD pathogenesis.

FUNDING: This study was supported by the National Natural Science Foundation of China(U22A20300, 82502244, 823714434, 82071216), the National Key R&D Program of China(2023YFC3603700), STI2030-Major Projects(2021ZD0201803), Outstanding Youth Fund of Hunan Provincial Natural Science Foundation(2024JJ2097), Youth Fund of Hunan Provincial Natural Science Foundation(2025JJ60696), Hunan Health Commission Grant(20232460), Postdoctoral Fellowship Program of CPSF(GZC20233185), China Postdoctoral Science Foundation (2025M772318), and the Scientific Research Program of FuRong Laboratory (2024PT5108).},
}

@article {pmid41762442,
year = {2026},
author = {Rai, S and Ray, SK and Mukherjee, S},
title = {In Silico evaluation of bioactive compounds as potential inhibitors targeting HIF-1α/VEGFA/BACE1 pathway against Alzheimer's disease.},
journal = {Journal of complementary & integrative medicine},
volume = {},
number = {},
pages = {},
pmid = {41762442},
issn = {1553-3840},
abstract = {BACKGROUND: Neurodegenerative disorders such as Alzheimer's disease (AD) are characterized by progressive neuronal degeneration, predominantly caused by the accumulation of amyloid-beta (Aβ) and neuroinflammatory processes. Hypoxia, characterized by diminished oxygen levels, intensifies these mechanisms by stimulating hypoxia-inducible factor 1-alpha (HIF-1α), potentially enhancing BACE1 enzyme activity and resulting in increased Aβ synthesis and render neurons especially susceptible to hypoxia, exacerbating disease progression. Existing therapies are constrained by inadequate medication distribution across the blood-brain barrier and associated adverse effects.

OBJECTIVES: This study aims to identify potential therapeutic agents targeting HIF-1α, VEGFA, BACE1 key molecules involved in AD by exploring neuroprotective effects of bioactive compounds like benzyl isothiocyanate (BITC), Aurantiamide Acetate (AA), and galantamine, with the goal of developing more effective, targeted treatments.

METHODSOLOGY: We used in silico screening, such as molecular docking and ADMET analysis, to assess the binding affinity, pharmacokinetics, and toxicity of potential inhibitors, followed by in vitro testing.

RESULTS AND DISCUSSION: Results identified several compounds with strong binding affinities and favorable ADMET profiles as potential inhibitors of HIF-1α, VEGFA, BACE1 and experimental data support that hypoxia, via HIF-1α, upregulates BACE1, increasing Aβ production and contributing to AD. Targeting these pathways may offer a multi-faceted approach to therapy, reducing neuroinflammation and amyloid pathology.

CONCLUSIONS: In silico screening of potential molecules across different pathogenic pathways in Alzheimer's disease shows promise in developing successful therapeutic methods and continued validation may result in more tailored and safer medicines that address underlying neurodegenerative pathways.},
}

@article {pmid41762421,
year = {2026},
author = {Atar, A and Şahin Anılgan, İN},
title = {Insulin Resistance as a Shared Pathophysiological Driver in Neurological Disorders: a Narrative Review.},
journal = {Current nutrition reports},
volume = {15},
number = {1},
pages = {},
pmid = {41762421},
issn = {2161-3311},
abstract = {PURPOSE OF REVIEW: Insulin resistance has traditionally been viewed as a peripheral metabolic abnormality; however, accumulating evidence indicates that impaired insulin signaling within the central nervous system plays a critical role in the pathogenesis of multiple neurological disorders. The purpose of this narrative review is to synthesize current evidence supporting insulin resistance as a shared pathophysiological driver across neurodegenerative, neurological, and neuropsychiatric conditions, and to evaluate the potential of nutrition- and metabolism-based interventions as modulatory strategies.

RECENT FINDINGS: Recent human and experimental studies demonstrate that central insulin resistance disrupts brain energy metabolism, promotes neuroinflammation, impairs synaptic plasticity, and alters neuronal network stability. These mechanisms contribute to disease onset and progression in Alzheimer's disease, Parkinson's disease, epilepsy, and mood disorders. Advances in neuroimaging, cerebrospinal fluid biomarkers, and molecular profiling have strengthened the link between impaired insulin signaling and cognitive, behavioral, and affective dysfunction. In parallel, emerging evidence suggests that dietary patterns, energy restriction, ketogenesis, and lifestyle interventions can partially restore insulin sensitivity, improve metabolic flexibility, and mitigate neurobiological vulnerability. Insulin resistance should be regarded not merely as a comorbid metabolic condition, but as an active disease-modifying factor in a broad spectrum of neurological disorders. Targeting insulin signaling pathways through personalized nutritional and metabolic interventions represents a promising, modifiable strategy for prevention and adjunctive management. Future research integrating metabolic phenotyping with neurological outcomes will be essential to translate these insights into clinical practice.},
}

@article {pmid41762146,
year = {2026},
author = {McKay, MH and Leeman, J and Fender, M and Ulmer, C and Towsley, G and Toles, M},
title = {Promoting Adaptation to Caregiving Challenges: A Qualitative Study of Dementia Caregiving Specialists.},
journal = {Journal of applied gerontology : the official journal of the Southern Gerontological Society},
volume = {},
number = {},
pages = {7334648261428750},
doi = {10.1177/07334648261428750},
pmid = {41762146},
issn = {1552-4523},
abstract = {Limited evidence describes how practicing dementia caregiving specialists (DCS) facilitate caregiver mastery of dementia-related challenges. This qualitative study was designed to characterize perceptions of a national sample of DCS about the caregiver support they provide and strategies they use to promote caregivers' adaptation to dementia caregiving challenges. Qualitative analysis of interviews with 27 DCS from 11 states indicates the scope of DCS practice ranged from one-to-one and group-based consultation to community education and advocacy. DCS reported providing care at inflection points such as care transitions. DCS supportive strategies to facilitate caregiver adaptation were classified into six themes, such as identifying immediate caregiving challenges, experimenting with adaptive solutions, and sustaining new solutions over time. Findings provide a framework to develop DCS training resources, design intervention models, and examine the impact of DCS support on patient and caregiver outcomes, such as outcomes during care transitions.},
}

@article {pmid41762118,
year = {2026},
author = {Liu, N and Yang, Y and Kritsilis, M and Swanberg, KM and Liu, C and Liu, X and Moonen, B and Deierborg, T and Nilsson, P and Syvänen, S and Sehlin, D and Lundgaard, I},
title = {Early glymphatic failure in AppNL-F knock-in mice is linked to parenchymal border macrophages loss.},
journal = {Brain : a journal of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1093/brain/awag080},
pmid = {41762118},
issn = {1460-2156},
abstract = {Amyloid-β (Aβ) accumulation is a hallmark of Alzheimer's disease. Cerebral Aβ deposition is attenuated by a functional glymphatic system, in which perivascular entry of cerebrospinal fluid (CSF) and its exchange with interstitial fluid mediate solute clearance. Parenchymal border macrophages (PBMs), positioned along glymphatic pathways, are emerging as important players for glymphatic clearance. However, how glymphatic function and PBMs are affected in App knock-in models of Alzheimer's disease is unknown. In this study, we used two App knock-in mouse models that develop progressive Aβ pathology, AppNL-F and AppNL-G-F. AppNL-F mice showed reductions in glymphatic influx and clearance at 6 months, preceding substantial Aβ plaque deposition. The decrease in glymphatic function in AppNL-F mice correlated with a loss of PBMs and altered marker expression. Acute administration of Aβ into the CSF decreased the number of PBMs and impaired glymphatic transport in wild-type mice, thus recapitulating the pre-plaque stage. In contrast, the number of PBMs was not reduced in AppNL-G-F mice, possibly due to an enhanced Aβ phagocytic capacity in PBMs. Four weeks of systemic anti-Aβ antibody treatment efficiently reduced Aβ plaque load and rescued PBMs in some brain regions, however, the treatment did not restore glymphatic function in the AppNL-F model. These findings suggest that glymphatic dysfunction in App knock-in models of Alzheimer's disease is not driven by parenchymal Aβ plaque load but is closely linked to pre-plaque Aβ-induced loss of PBMs. Preservation of PBM abundance and their normal marker expression may be important for maintaining glymphatic function and mitigating early progression of Alzheimer's disease.},
}

@article {pmid41762056,
year = {2026},
author = {Chen, Q and Fu, Y and Hu, L and Chen, X and Liu, Z},
title = {Draxin Induces Cognitive Impairment in Mice via Wnt/β-Catenin-Mediated Tau Phosphorylation.},
journal = {Journal of integrative neuroscience},
volume = {25},
number = {2},
pages = {47749},
doi = {10.31083/JIN47749},
pmid = {41762056},
issn = {0219-6352},
support = {2024A1515220002//Guangdong Provincial Basic and Applied Basic Research Fund/ ; 4SG23284G//Clinical + Basic Research Project of Guangdong Medical University/ ; GDMULCJC2024003//Clinical + Basic Research Project of Guangdong Medical University/ ; GDMULCJC2024036//Clinical + Basic Research Project of Guangdong Medical University/ ; LCYJ2020B009//Affiliated Hospital of Guangdong Medical University/ ; 2024HY-A6006//Guangdong Provincial Medical Association Clinical Research Fund - Healthcare Special/ ; 4SG22307P//2023 Special Project of the Songshan Lake Medical-Engineering Integration Innovation Center of Guangdong Medical University/ ; GCC2022011//Guangdong Medical University Affiliated Hospital High level Talent Research Launch Fund/ ; 2020B01395//Science and Technology Planning Project of Zhanjiang/ ; 2020B01421//Science and Technology Planning Project of Zhanjiang/ ; GDMUQ2021047//Science and Technology Planning Project of GDMU/ ; GDMU2021122//Science and Technology Planning Project of GDMU/ ; },
abstract = {BACKGROUND: Dorsal repellent axon guidance protein (draxin) is a secreted protein that plays an establishment role in the formation of proper connections between neurons. Although draxin is known to regulate the elongation of axons from various types of neurons in vitro, its specific role in mature neurons remains unclear. Draxin expression in the hippocampal region of patients with Alzheimer's disease (AD) has been reported to be higher than in normal subjects. The present study investigated the effect of draxin on the expression of microtubule-associated protein 2 (MAP2) and neuronal nuclear antigen (NeuN), and on tau protein phosphorylation in mouse hippocampal neurons (HT22 cells) and AD cellular models. In addition, stereotactic techniques were used to inject neuronal-targeted adeno-associated virus (AAV) into the hippocampus of C57BL/6 mice to assess the effects of draxin overexpression on hippocampal neurons, as well as on behavioral and pathological features.

METHODS: In vitro experiments were conducted using mouse hippocampal neuronal cells (HT22 cells) and established AD cellular models, focusing on evaluating draxin's effects on the expression of neuronal markers (MAP2 and NeuN) and the phosphorylation status of tau protein. For in vivo validation, neuron-targeted AAV was delivered into the hippocampus of C57BL/6 mice via brain stereotactic injection to achieve draxin overexpression. Subsequent assessments included analyses of hippocampal neuronal integrity, behavioral tests (Y-maze and Morris water maze, to evaluate spatial learning and memory), and detection of AD-related pathological markers.

RESULTS: In vitro experiments revealed that draxin overexpression decreased the cell survival rate, increased the apoptosis rate, decreased the expression of MAP2 and NeuN, and showed a trend for increased phosphorylation of tau protein compared with the control group. Notably, the spatial learning memory ability of mice with draxin overexpression in the brain, as determined by the Y-maze and Morris water maze tests, was significantly diminished compared with the control group. These mice also showed elevated tau protein phosphorylation and altered expression of wingless-related integration site (Wnt)/β-catenin/glycogen Synthase Kinase 3 beta (GSK-3β) pathway components.

CONCLUSIONS: Our results suggest for the first time that neuronal overexpression of draxin may induce neuronal damage via the Wnt/β-catenin/GSK-3β signaling pathway, leading to AD-like neuropathological damage and cognitive dysfunction.},
}

@article {pmid41762055,
year = {2026},
author = {Yang, D and Liu, L and Fu, J},
title = {Therapeutic Potential of Nerve Growth Factor-Modified Hair Follicle Stem Cells Transplantation in a Rat Model of Alzheimer's Disease.},
journal = {Journal of integrative neuroscience},
volume = {25},
number = {2},
pages = {43410},
doi = {10.31083/JIN43410},
pmid = {41762055},
issn = {0219-6352},
abstract = {BACKGROUND: Alzheimer's disease (AD) is a degenerative condition affecting the central nervous system and is the primary cause of dementia. Current therapies for AD are ineffective. Although brain regeneration via stem cell transplantation has therapeutic potential, suitable sources are limited. Hair follicle stem cells (HFSCs) are multi-potent cells and can differentiate into mesodermal and ectodermal lineages, and proliferate for extended periods. Nerve growth factor (NGF) is a neurotrophin that is vital for neuronal development and survival, and the regulation of apoptosis in neurodegenerative disorders. However, using HFSCs to treat AD has not been extensively investigated. Herein, we evaluated the therapeutic effects of HFSCs and the synergistic effect of NGF and HFSCs on AD.

METHODS: A rat model of AD was established by intrahippocampal injection of amyloid β-protein 1-42 (Aβ1-42). After 14 days, HFSCs and HFSCs overexpressing NGF were injected into the hippocampus of AD rats for therapy. The cognitive function of the treated AD rats was tested using the Morris water maze test. Congo red staining, immunohistochemistry, and enzyme-linked immunosorbent assay (ELISA) were used to detect deposition, as well as soluble Aβ1-40 and Aβ1-42 levels. Additionally, western blotting was used to assess tau protein, the phosphoinositide-3 kinase (PI3K)/protein kinase B/glycogen synthase kinase-3β (Akt/GSK-3β) pathway, and the levels of synapse proteins.

RESULTS: HFSCs and HFSCs/NGF transplantation not only significantly reduced Aβ deposition but also inhibited GSK-3β activity and reduced tau protein hyperphosphorylation by stimulating the PI3K/Akt signaling pathway. Moreover, HFSC and HFSC/NGF transplantation led to significant overexpression of the synaptophysin (SYP) and postsynaptic density protein 95 (PSD95) in the hippocampus of AD rats.

CONCLUSIONS: HFSCs and NGF-modified HFSCs may become a promising treatment option for AD.},
}

@article {pmid41762050,
year = {2026},
author = {Wang, A and Li, J and Liu, H and Yue, D},
title = {Physiological Regulatory Mechanisms of Neurovascular Coupling and the Role of Its Dysfunction in Neurological Diseases.},
journal = {Journal of integrative neuroscience},
volume = {25},
number = {2},
pages = {42796},
doi = {10.31083/JIN42796},
pmid = {41762050},
issn = {0219-6352},
support = {202401AY070001-245//Joint Special Project of Kunming Medical University-General Project/ ; },
abstract = {Neurovascular coupling (NVC) is a fundamental physiological process that regulates cerebral blood flow in response to neuronal activity. This mechanism ensures the efficient delivery of oxygen and glucose to active brain regions while clearing metabolic byproducts, thus maintaining brain homeostasis and supporting optimal neural function. Disruptions in NVC are linked to complex molecular and cellular alterations and contribute significantly to a range of both acute and chronic neurological disorders, including Alzheimer's disease, ischemic stroke, cerebral small vessel disease, migraines, epilepsy, and cognitive deficits associated with diabetes. Gaining a deeper understanding of the pathological mechanisms underlying NVC dysfunction in these conditions is critical for developing novel diagnostic biomarkers and targeted therapeutic strategies. This review aims to provide a comprehensive exploration of the physiological basis of NVC in a healthy brain, alongside the methods used to study it. Additionally, it offers a detailed analysis of the molecular and cellular mechanisms driving NVC dysfunction in major neurological diseases, presenting a theoretical framework and new insights for the development of innovative diagnostic and therapeutic interventions.},
}

@article {pmid41762024,
year = {2026},
author = {Sreekumari, GR and Ng, ST and Chen, RPY and Koshy, KC and Baby, S},
title = {A novel dual-action compound from the Western Ghats tree Poeciloneuron indicum targets acetylcholinesterase and neprilysin in Alzheimer's disease.},
journal = {Natural product research},
volume = {},
number = {},
pages = {1-6},
doi = {10.1080/14786419.2026.2636157},
pmid = {41762024},
issn = {1478-6427},
abstract = {A new caprolactone derivative, (Z)-7-(16-hydroxyhexadecyl)-3-(propoxycarbonyl)oxepan-4-en-2-one (poecilone A), was isolated from the leaves of Poeciloneuron indicum, an endemic tree of the Western Ghats in India. Poecilone A exhibited dose-dependent inhibition of acetylcholinesterase (AChE) with an IC50 value of 2.23 µM. Fluorescence-based assays demonstrated that poecilone A promotes amyloid beta (Aβ) degradation and inhibits Aβ aggregation. Specifically, neprilysin (NEP) and insulin-degrading enzyme (IDE) cleave qf-Aβ(1-7)C, while NEP and angiotensin-converting enzyme (ACE) target qf-Aβ(12-16)AAC. At concentrations of 5.0 and 7.5 µM, poecilone A increased fluorescence in both peptide cleavage assays, suggesting a potential enhancement of NEP-associated enzymatic activity. These dual activities of AChE inhibition and NEP upregulation highlight poecilone A as a promising natural lead compound for the mitigation of Alzheimer's disease.},
}

@article {pmid41761874,
year = {2026},
author = {Nilsson, N and Salmi, T and Viikki, M and Palmio, J and Collin, P and Huhtala, H and Koskinen, I and Kaukinen, K and Reunala, T and Hervonen, K and Pasternack, C},
title = {Cohort study of neurological and psychiatric morbidity in dermatitis herpetiformis and celiac disease.},
journal = {Scandinavian journal of gastroenterology},
volume = {},
number = {},
pages = {1-10},
doi = {10.1080/00365521.2026.2636062},
pmid = {41761874},
issn = {1502-7708},
abstract = {BACKGROUND: Neurological and psychiatric morbidity has been associated with celiac disease but has been scarcely studied in dermatitis herpetiformis (DH), a cutaneous manifestation of celiac disease. Hence, this cohort study aimed to investigate neurological and psychiatric morbidity in patients with DH and celiac disease.

METHODS: The study comprised 368 DH patients and 1,072 celiac disease patients without DH and their 1,099 and 3,197 refences, matched 1:3 on age, sex, calendar period and place of residence. Their neurological and psychiatric morbidity was studied using the Care Register for Health Care and international classification of diseases codes. Hazard ratios (HR) were calculated using Cox proportional hazard model.

RESULTS: In DH the risk for any neurological disease was not statistically significantly increased (HR 1.27; 95% CI 0.94-1.71), but Alzheimer's disease and extrapyramidal diseases were found to be more common in DH when compared with their references. In contrast, in celiac disease excess risks for any neurological disease (HR 1.31; 95% CI 1.09-1.56) and particularly for migraine and headaches were detected. The risk for any psychiatric disease was found to be decreased in DH (HR 0.65; 95% CI 0.47-0.90), as were the risks for anxiety and substance abuse. In celiac disease, increased risks for any psychiatric disease (HR 1.20; 95% CI 1.01-1.42), depression, and anxiety disorders were noted.

CONCLUSIONS: The neurological and psychiatric morbidity of patients with DH and celiac disease patients without DH seems to differ, but the reasons for this varying disease burden remain yet unidentified.},
}

@article {pmid41761870,
year = {2026},
author = {Qin, H and Pointon, L and Carpenter, J and Raymont, V and Dunne, R and Reeves, S and Ali, S and Iqbal, S and Bonet-Olivares, C and Whittle, J and Rizzo, L and Malhotra, P and Underwood, BR and , },
title = {Patient and public involvement and engagement in clinical trials at scale: Analysis of the first 3250 responses on the POrtal for Patient and Public Engagement in Dementia (POPPED).},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {2},
pages = {e71113},
pmid = {41761870},
issn = {1552-5279},
support = {NIHR203312//National Institute for Health and Care Research (NIHR) Cambridge Biomedical Research Centre/ ; ARUK-SPON2024-001//Alzheimer's Research UK Scientific Conference Sponsorship/ ; NIHR165710//Efficacy and Mechanism Evaluation Programme/ ; },
abstract = {INTRODUCTION: Patient and public involvement and engagement (PPIE) improves research quality but is often limited in scale. This study explored the potential for large-scale PPIE using a Web-based approach.

METHODS: We created an online portal to gather public views on dementia research and a UK-based adaptive platform trial testing repurposed Alzheimer's disease drugs. Participants ranked four anonymized drugs and completed discrete choice experiments on treatment trade-offs. Analyses were stratified by sex, age, and dementia experience.

RESULTS: Among 3250 people across 27 countries (87.4% UK-based), 79.6% expressed positive attitudes toward the trial. Metformin was the most preferred drug, followed by atomoxetine, isosorbide mononitrate, and levetiracetam. Probability of severe side effects was the most influential treatment attribute, followed by probability of mild side effects and type of evidence. Subgroup analyses supported the main findings.

DISCUSSION: Web-based PPIE can effectively inform dementia research at scale and provides a reusable resource for other studies.},
}

@article {pmid41761858,
year = {2026},
author = {Luo, H and Mei, W and Ye, J and Liu, L and Liang, W and Shu, Y},
title = {Causal effects of gestational hypertension on women's health: A Mendelian randomization analysis.},
journal = {International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics},
volume = {},
number = {},
pages = {},
doi = {10.1002/ijgo.70897},
pmid = {41761858},
issn = {1879-3479},
abstract = {OBJECTIVE: Gestational hypertension (GH) is linked to complications impacting women's health, with confounded causal links in observational studies. This study used Mendelian randomization (MR) to investigate GH's effects on women's diseases.

METHODS: To reduce confounding and identify robust GH associations, we selected 149 single-nucleotide polymorphisms (SNPs) as instrumental variables (IVs). The data were extracted from publicly accessible genome-wide association studies (GWAS). The inverse-variance weighted (IVW) method served as the primary MR analysis, with sensitivity verification conducted through MR-Egger, weighted median, weighted mode, and simple mode analyses.

RESULTS: MR analysis found no significant causal links between GH and postpartum conditions, such as mental and behavioral disorders, postpartum hemorrhage, puerperal sepsis, or depression. However, GH significantly increased stroke risk in women (PIVW = 0.0103, odds ratio [OR]: 1.009, 95% confidence interval [CI:] 1.002-1.016). No causal relationships were detected between GH and Alzheimer's, severe depression, Parkinson's, diabetes, gestational diabetes, polycystic ovary syndrome (PCOS), or cancers, including ovarian, bowel, cervical, endometrial, breast, and lung cancer. Sensitivity analyses showed no pleiotropic effects.

CONCLUSION: GH is causatively linked to higher stroke risk in women, underscoring the need for focused monitoring and interventions to mitigate long-term health risks in this group.},
}

@article {pmid41761844,
year = {2026},
author = {Carlozzi, NE and Fansher, M and Troost, JP and Miner, JA and Tsuker, S and Leggett, AN},
title = {Validating the Use of TBI-CareQOL Measures in Caregivers of People Living With Dementia.},
journal = {American journal of Alzheimer's disease and other dementias},
volume = {41},
number = {},
pages = {15333175261426872},
doi = {10.1177/15333175261426872},
pmid = {41761844},
issn = {1938-2731},
abstract = {Understanding the clinical utility of patient-reported outcome measures is critical for using these measures in research and clinical practice. Therefore, the purpose of this analysis was to establish the psychometric properties of three TBI-CareQOL measures in caregivers of people living with Alzheimer's disease or Alzheimer's disease-related dementias (ADRD): Caregiver Strain, Caregiver-Specific Anxiety, and Feeling Trapped. One-hundred-and-ninety-seven caregivers of individuals living with ADRD (n=197) completed three TBI-CareQOL measures, three additional measures to establish convergent and discriminant validity (NIH Toolbox Perceived Stress, Dementia Management Strategies Scale, PROMIS Pain Intensity), and the Dementia Severity Rating Scale to establish known groups validity. Internal consistency and test-retest reliability of the TBI-CareQOL measures were supported (alphas >.70). The TBI-CareQOL measures were also free of floor and ceiling effects. Convergent, discriminant, and known groups validity were also supported. Taken together, findings support the clinical utility of the TBI-CareQOL measures for caregivers of people living with ADRD.},
}

@article {pmid41761842,
year = {2026},
author = {Lakas, M and Sifi, I and Kadi, I and Eloff, JN},
title = {In vitro and in silico inhibition of acetylcholinesterase by acetone extracts of Anvillea garcinii subsp. radiata (Coss. & Durieu) Anderb., Marrubium deserti (de Noé) Coss., and Asphodelus tenuifolius Cav. from the Algerian desert.},
journal = {Natural product research},
volume = {},
number = {},
pages = {1-12},
doi = {10.1080/14786419.2026.2632381},
pmid = {41761842},
issn = {1478-6427},
abstract = {The complex pathophysiology of Alzheimer's disease underscores the need for potent AChE inhibitors. In this context, we investigated, for the first time, the acetone extracts of three Algerian medicinal plants: Anvillea garcinii subsp. radiata (Coss. & Durieu) Anderb., Marrubium deserti (de Noé) Coss., and Asphodelus tenuifolius Cav., through combined in vitro AChE assays, LC-MS/MS metabolite profiling and in silico evaluation. Total phenolic and flavonoid content analyses revealed that M. deserti had the highest levels TPC/TFC (209.8 ± 0.6 mgGAE/g and 161.0 ± 0.9 mgQE/g, respectively). In vitro AChE inhibition assays, showed that galantamine exhibited the strongest activity (4.23 ± 0.02 μg/mL) followed by the A. garcinii subsp. radiata (IC50=122.88 ± 1.30 µg/mL). LC-MS/MS profiling identified 21 compounds, with A. garcinii subsp. radiata displaying the most diverse chemical profile. Molecular docking analysis revealed strong binding affinities, with hesperidin exhibiting the highest binding energy (-11.2 kcal/mol), comparable to the reference drug donepezil (-11.5 kcal/mol).},
}

@article {pmid41761793,
year = {2026},
author = {Deng, X and Zeng, Y and Ding, D},
title = {Comparative assessment of donepezil memantine and sodium oligomannate on cognitive decline and neuroinflammation in early Alzheimer's disease.},
journal = {Pakistan journal of pharmaceutical sciences},
volume = {39},
number = {4},
pages = {944-957},
doi = {10.36721/PJPS.2026.39.4.REG.15270.1},
pmid = {41761793},
issn = {1011-601X},
abstract = {BACKGROUND: Early Alzheimer's disease (AD) treatments include donepezil, memantine and sodium oligomannate, but their comparative effects on cognitive decline and neuroinflammation are understudied.

OBJECTIVES: This study compares three drugs' validity in improving two aspects in early AD patients.

METHODS: 132 early AD patients from XX Hospital (Jan 2022-Dec 2024) were retrospectively included. After exclusion, 126 patients were divided into 3 groups (42 each): Group A (donepezil), Group B (memantine), Group C (sodium oligomannate). Cognitive function was assessed using the Mini-Mental State Examination (MMSE), the Alzheimer's Disease Assessment Scale--Cognitive Subscale (ADAS-cog), the Activity of Daily Living Scale (ADL), the Montreal Cognitive Assessment Scale (MoCA), levels of inflammatory mediators, including Tumour Necrosis Factor-α (TNF-α), interleukin-6 (IL-6), interleukin-8 (IL-8), neuronal marker levels including β-Amyloid (1-42) (Aβ42), Total tau protein (T-tau protein) and adverse reaction incidence.

RESULTS: After treatment, compared with Group A, Groups B/C had significantly higher MMSE, ADL, MoCA, Aβ42 (all P<0.05) and lower ADAS-cog, TNF-α, IL-6, IL-8, T-tau (all P<0.05); compared with Group B, Group C had no significant difference in MMSE, ADAS-cog, ADL, MoCA (all P>0.05), but higher Aβ42 and lower TNF-α, IL-6, IL-8, T-tau (all P<0.05); adverse reaction incidence did not differ significantly among the three groups (P>0.05).

CONCLUSION: Memantine and sodium oligomannate outperform donepezil in improving cognitive function and neuroinflammation, with sodium oligomannate suggesting the best effect on neuroinflammation. This study provides a scientific basis for optimizing early AD medication.},
}

@article {pmid41761646,
year = {2026},
author = {Chen, Y and Jie, W and Xu, Y and Chen, X and Zhu, S and Ma, Y and Hu, L and Chen, C and Liu, B and Xu, D and Cai, D and Liu, Z},
title = {Correlation study between gut microbiota and intestinal permeability in cerebral small vessel disease.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261418554},
doi = {10.1177/13872877261418554},
pmid = {41761646},
issn = {1875-8908},
abstract = {BackgroundDysbiosis of gut microbiota and increased intestinal permeability are associated with various diseases, and their relationship with cognitive dysfunction such as cerebral small vessel disease (CSVD) and Alzheimer's disease remains to be elucidated.ObjectiveThis study investigates the role of gut microbiota dysbiosis and its relationship with intestinal permeability in patients with cognitive impairment associated with CSVD (CSVD-CI).MethodsIntestinal permeability was detected in 21 patients with CSVD-CI and 20 healthy controls by testing urine lactulose/mannitol, and correlation analysis was performed between the test results and cognitive function assessment. 16S rRNA sequencing was used to analyze the different combination of gut microbiota. Feces of the patients or controls were gavaged into C57 mice, and gut barrier function, behavior, and metabolites were assessed.ResultsPatients with CSVD-CI have a higher incidence of hypertension, higher homocysteine levels, higher scores for white matter hyperintensities, and worse cognitive function. Their urinary mannitol recovery rate is higher, which is correlated with lower scores of cognitive function assessment. Alterations in the gut microbiota involve a reduction in Prevotella-9 alongside increases in Proteobacteria and Fusobacteria. Fecal microbiota transplantation (FMT) from patients with CSVD-CI increases intestinal permeability in mice, but does not change their cognitive function; meanwhile, fecal metabolomics analysis has identified alterations in bile acids and vitamins, which are associated with shifts in the gut microbiota.ConclusionsPatients with CSVD-CI have gut microbiota imbalance and increased intestinal permeability, which are associated with cognitive decline. FMT from these patients can cause intestinal leakage and the production of harmful metabolites in mice.},
}

@article {pmid41761645,
year = {2026},
author = {Bissar, N and Kassir, R and Missilmani, F and Salem-Sokhn, E and Shamieh, SE},
title = {Association of post-transcriptional regulatory gene single nucleotide polymorphisms with Alzheimer's disease.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261424256},
doi = {10.1177/13872877261424256},
pmid = {41761645},
issn = {1875-8908},
abstract = {BackgroundAlzheimer's disease (AD) is a progressive neurodegenerative characterized by amyloid-β (Aβ) peptide aggregation and tangles. Protein translation deregulation and viral exposures, including SARS-CoV-2, have been implicated in increased AD risk. Genes such as YIF1A, PABPC4, and MRPS27, which are involved in mRNA translation and protein folding have been linked to neurodegeneration and host responses to SARS-CoV-2.ObjectiveThis study investigates the association of three genetic variants, rs7945723G>A, rs6587A>G, and rs6831A>G, respectively correlated with YIF1A, PABPC4, and MRPS27, with AD, and explored their expression in COVID-19 samples to assess potential shared pathways.MethodsA KASP genotyping assay was performed on 127 AD patients and 250 controls. A Binary logistic regression model assessed the association between AD and the single nucleotide polymorphisms, adjusting for age, sex, body mass index, and education. Gene expression was quantified by RT-qPCR in nasopharyngeal samples from 32 COVID-19 patients and 39 controls. The Mann- Whitney test compared gene expression between groups, and logistic regression evaluated associations with COVID-19 status.ResultsResults showed that rs6587A>G in PABPC4 is significantly associated with AD risk with the GG genotype conferring increased susceptibility (OR = 4.3, p = 0.010). Gene expression analysis revealed no significant differences in PABPC4, YIF1A, or MRPS27 between COVID-19 and control groups.ConclusionsOur findings suggest that post-transcriptional regulatory mechanisms, particularly involving PABPC4, may contribute to AD-related pathways. Larger multi-ethnic cohorts and functional studies are needed to clarify the role of PABPC4 and potential shared mechanisms between AD and COVID-19.},
}

@article {pmid41761644,
year = {2026},
author = {Kim, M 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 = {APOE4-dependent association between metformin use and Alzheimer's disease-related cortical thickness in older adults with type 2 diabetes.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261418688},
doi = {10.1177/13872877261418688},
pmid = {41761644},
issn = {1875-8908},
abstract = {BackgroundMetformin has been proposed to have neuroprotective benefits, but its effects on AD-related brain changes remain unclear and may be influenced by apolipoprotein E ε4 (APOE4) genotype, a major genetic risk factor for AD.ObjectiveTo examine the association between metformin use and in vivo AD pathologies and to evaluate whether APOE4 status moderates these associations in older adults with type 2 diabetes mellitus (T2DM).MethodsThis cross-sectional study used baseline data from 76 non-demented older adults with T2DM (aged 55-90 years), who were enrolled in the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer's Disease (KBASE). The participants underwent comprehensive clinical and neuropsychological assessment and multimodal neuroimaging, including global amyloid- β (Aβ) retention ([[11]C] PiB-PET), inferior temporal tau deposition ([[18]F] AV-1451 PET), AD-signature cortical thickness (AD-CT), and white matter hyperintensity (WMH) volume. Global cognition was assessed using the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropsychological battery.ResultsAmong 76 participants, 55 (72%) were metformin users and 21 (28%) were non-users. Metformin use was significantly associated with greater AD-CT, but not with Aβ, tau, or WMH volume. A significant interaction between metformin use and APOE4 status was observed with respect to AD-CT. In APOE4-stratified analyses, metformin use was significantly associated with greater AD-CT and better global cognition among APOE4 non-carriers, but not among carriers.ConclusionsOur findings indicate that metformin use is associated with greater AD-CT-independently of amyloid or tau pathology-particularly among APOE4 non-carriers, and this structural preservation is accompanied by better cognitive outcomes.},
}

@article {pmid41761642,
year = {2026},
author = {Novak, DA and Saleem, N and Gerhardt, PC and Maestas, D and Kejriwal, N and Vaezazizi, E and Murray, I and Al-Khoury, L},
title = {Alzheimer's disease in patients prescribed statins: A real-world data analysis of U.S. patient health records.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261424220},
doi = {10.1177/13872877261424220},
pmid = {41761642},
issn = {1875-8908},
abstract = {BackgroundEvidence from observational studies and randomized controlled trials (RCTs) remains discordant on the impact of statin therapy on long-term outcomes related to Alzheimer's disease. Observational studies find relatively large effect sizes; RCTs fail to demonstrate cognitive benefits. Methodological limitations in both approaches may explain the disconnect.ObjectiveTo bridge the gap between observational and RCT studies, this study uses Real World Data (RWD) to evaluate the association between statin use and incident AD risk, and contributes additional detailed stratification by statin type and dosage.MethodsThis observational analysis of EHR data from over 125 million U.S. patients through the TriNetX platform compared statin exposure in adults over 45 years old with a diagnosis of dyslipidemia, and no prior AD diagnosis, controlling for demographics, a range of known comorbidities, laboratory values, and medications. Primary outcomes were incident AD, other degenerative neurological diseases, and all-cause mortality. Sub-analyses compared risks by statin type and dosage.ResultsStatin exposure was associated with a substantially lower risk of incident AD compared with non-exposure (RR = 0.69), similar to meta analyses of observational studies. Lipophilic and hydrophilic statins showed reduced AD risk compared to controls; hydrophilic statins showed a slightly greater protective effect. High-dose and low/medium-dose statins conferred similar risk reductions with no significant dose-dependent difference.ConclusionsOur findings provide evidence that statin therapy is associated with reduced risk of AD and related outcomes, extending prior observational data with broader population representation and rigorous confounder control. Pending further evidence, statins may be considered as part of comprehensive strategies to reduce AD risk.},
}

@article {pmid41761618,
year = {2026},
author = {Hasmukharay, K and Ming Hui, H and Mahyudin, NA and Salleh, A and Kukreja, A and Wong, PL and Meng Li, C and Ong, EJ and Xin Woen, T and Hisham, S and Verma, AK and Lovero, KL and Ross, J and Rajasuriar, R},
title = {Is Cognitive Care the Next Blind Spot in HIV Clinical Practice? Exploring the Facilitators and Barriers to Integrating Cognitive Care into Routine HIV Care in Malaysia: A Mixed Method Study.},
journal = {AIDS patient care and STDs},
volume = {},
number = {},
pages = {10872914261423775},
doi = {10.1177/10872914261423775},
pmid = {41761618},
issn = {1557-7449},
abstract = {In the antiretroviral therapy era, as people living with HIV (PWH) age, the decline of HIV-associated dementia has been accompanied by a growing burden of earlier Alzheimer-type pathology and other milder, heterogeneous cognitive impairments, underscoring the need for proactive detection and multidisciplinary management within routine HIV care. Yet, cognitive care remains largely absent, particularly in low- and middle-income countries (LMIC). We evaluated readiness to integrate a multidomain cognitive-rehabilitation program into tertiary HIV clinic in Malaysia and identified implementation determinants. We used a sequential mixed-methods design. An online Knowledge-Attitude-Practice survey was distributed to all infectious-disease physicians nationwide (N = 94). Qualitative data were generated through focus-group discussions with health care providers (HCPs) and in-depth interviews with PWH aged >40 years. Transcripts were analyzed thematically using the Consolidated Framework for Implementation Research (CFIR 2.0). Forty-nine physicians responded (52.4% response), median age was 44 years (inter-quartile range (IQR) 38-51), and 71.4% were female. While 71-82% demonstrated satisfactory knowledge and attitudes toward cognitive health, 88% reported poor practice; only 20.5% routinely screened older PWH. Thirty-three HCPs from multidisciplinary backgrounds participated in five focus groups, alongside 19 in-depth interviews with PWH. Three interlinked domains emerged: (1) knowledge-practice gap related to uncertainty around screening tools, referral pathways, and evidence applicability; (2) systemic barriers including time constraints, high caseloads, lack of guidelines, and workforce limitations; and (3) stigma affecting acceptability. Facilitators included strong patient motivation for brain health, allied health upskilling, physician-initiated referrals, and dedicated care coordination. Integration of multidisciplinary cognitive rehabilitation is hindered by modifiable structural deficits in knowledge translation, workforce organization, and guideline support. HIV-adapted screening algorithms, formalized referral processes, and task-shared coordinator roles could enable earlier cognitive interventions for older adults living with HIV in Malaysia and similar LMIC settings.},
}

@article {pmid41761572,
year = {2026},
author = {Huang, Y and Li, Y and Lou, X and Islam, JY and Liang, M and George, TJ and Bian, J and Guo, Y},
title = {Breast cancer screening and cancer prognosis in patients with Alzheimer's disease and related dementias.},
journal = {JNCI cancer spectrum},
volume = {},
number = {},
pages = {},
doi = {10.1093/jncics/pkag019},
pmid = {41761572},
issn = {2515-5091},
abstract = {BACKGROUND: Breast cancer screening is crucial for early detection and improved survival in Alzheimer's Disease and Related Dementias (ADRD) patients, but real-world evidence of its effects on survival and prognosis remains insufficient.

METHODS: We conducted a retrospective cohort study using Surveillance, Epidemiology, and End Results-Medicare data (1999 to 2019) to analyze the impact of breast cancer screening on prognosis (ie cancer stage) and survival in ADRD women with breast cancer diagnosed ≥ 67 years. Logistic and Cox regression models were employed to assess the relationship between screening and risk of advanced stage at diagnosis, and length of survival, adjusted for relevant covariates (e.x. marital status, comorbidities, age at screening).

RESULTS: The cohort included 8,739 ADRD patients with breast cancer, with 4,483 completed at least one screening between their ADRD and first breast cancer diagnosis. The cohort completed screening had significant lower rates of advanced-stage diagnosis (22.2% vs 42.6%) and longer survival (65.9 vs 45.7 months) compared to the cohort without any screening history. Unscreened patients had 2.7 times higher odds of advanced-stage diagnosis, and 2 times higher hazard of death than patients with at least one screening completed before breast cancer diagnosis. Effects of comorbidities, age, and race were significant on both diagnosis stage and survival in breast cancer patients.

CONCLUSION: Our study demonstrated the benefit of screening in early diagnosis and longer survival in ADRD patients with breast cancer, which advocates for an expansion of current breast cancer screening recommendations to more effectively guide cancer care for ADRD patients.},
}

@article {pmid41761426,
year = {2026},
author = {Tripathi, SM and Chutia, P and Shahi, MK and Supranjali, S and Shukla, R and Basu Roy, R},
title = {Punding in dementia: an insight into its occurrence, clinical characteristics, treatment, and outcome.},
journal = {Neurodegenerative disease management},
volume = {},
number = {},
pages = {1-9},
doi = {10.1080/17582024.2026.2637429},
pmid = {41761426},
issn = {1758-2032},
abstract = {AIM: This study investigates punding in dementia, its characteristics, treatment options, and outcomes.

METHODS: In this retrospective hospital-based study of 55 dementia patients, punding severity, cognition, and neuropsychiatric symptoms assessed using Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale, Hindi Mental Status Examination, and Neuropsychiatric Inventory were collected from baseline to week 8 after treatment. Chi-square and independent t-tests were used to compare groups and repeated measures ANOVA was used to investigate the change in rating scale scores on treatment.

RESULTS: The mean age of the patients was 72.8 ± 6.7 years, and 76.4% were of Alzheimer's disease. The frequency of punding in this hospital-based cohort was 61.8%. The mean duration of punding was 4.09 + 2.7 months, and repeated handling of clothes was the prominent characteristic. The patients were treated with low-dose risperidone and SSRI and significant improvement in the severity scores of punding was observed following treatment initiation.

CONCLUSION: Punding is a prevalent behavior in hospitalized patients with dementia. Rapid improvement in punding behavior was observed with combination pharmacotherapy of low dose SSRI and risperidone in our clinical sample. Further multicentric prospective controlled trials are required to establish treatment efficacy of this combination treatment for punding in dementia.},
}

@article {pmid41761363,
year = {2026},
author = {Zhou, Z and Zhang, W and Zhai, Z and Kong, F and Zhao, Y and Xu, Y and Sun, T},
title = {Effect and potential mechanism of photobiomodulation therapy on cognitive deficits in animal models of Alzheimer's disease: a systematic review and meta-analysis.},
journal = {European journal of medical research},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40001-026-04057-w},
pmid = {41761363},
issn = {2047-783X},
support = {No. 2021YJ0178//Sichuan Science and Technology Program/ ; No. 2020GFW194//Sichuan Science and Technology Program/ ; No. 2024MS594//the Scientific Research Special Project of Sichuan Administration of Traditional Chinese Medicine/ ; No. WXLH202403023//Joint Innovation Fund Project between Chengdu Municipal Health Commission and Chengdu University of TCM/ ; No. WXLH202403193//Joint Innovation Fund Project between Chengdu Municipal Health Commission and Chengdu University of TCM/ ; No. ZRQN2020008//Xinglin Scholar Research Promotion Project of Chengdu University of TCM/ ; },
abstract = {BACKGROUND: As a progressive neurodegenerative disorder, Alzheimer's disease (AD) has limited effective therapeutic options. Photobiomodulation (PBM) therapy, a non-invasive light therapy, represents a potential strategy for neurological diseases; however, its preclinical findings have been inconsistent. While previous reviews have summarized PBM's potential, this study is the first quantitative meta-analysis synthesizing preclinical evidence of PBM therapy in AD animal models, evaluating its effects on cognitive and neuropathological outcomes.

METHODS: We performed a systematic search across seven electronic databases to identify all relevant studies. A meta-analysis of 16 eligible studies evaluated the effects of PBM on cognitive outcomes and key neuropathological markers. Subgroup analyses were stratified by animal model and interventions (wavelength, energy density).

RESULTS: From 16 eligible studies, the meta-analysis found that PBM therapy significantly improved cognitive function (e.g., learning ability: MD =  - 7.18; 95% CI  - 9.87 to - 4.48), based on data from 386 animals. However, this was associated with significant heterogeneity (I[2] = 88%, p < 0.00001). PBM also significantly reduced Aβ deposition (SMD =  - 0.96; I[2] = 55%) and p-Tau levels (SMD =  - 2.24; I[2] = 14%). From a mechanistic standpoint, the activity of cytochrome c oxidase (CCO) is enhanced by PBM therapy. Subgroup analysis by animal model showed that PBM therapy was associated with greater improvement of learning and memory ability in transgenic animals. In different wavelengths, PBM using wavelengths greater than 750 nm showed numerically greater effects on learning ability. In different energy densities, PBM with an energy density less than or equal to 3 J/cm[2] was associated with greater improvement in learning ability and memory ability.

CONCLUSIONS: This meta-analysis demonstrates that PBM has significant therapeutic potential for AD animal models by improving cognition and ameliorating key pathologies. The mechanisms likely involve mitigating oxidative stress and enhancing mitochondrial function. While preclinical evidence strongly supports the efficacy of PBM, translation to humans requires careful optimization of treatment parameters and dose-response relationships. Further high-quality preclinical trials are crucial to validate the therapeutic potential of PBM for AD.},
}

@article {pmid41761301,
year = {2026},
author = {Liu, WZ and Xue, M and Sheng, ZH and Wei, YQ and Ma, YH and Li, JQ and Song, JH and Chi, S and Ou, YN and , },
title = {Baseline plasma p-tau217/Aβ42 as a sensitive marker for the severity of Alzheimer's disease continuum.},
journal = {Journal of translational medicine},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12967-026-07939-z},
pmid = {41761301},
issn = {1479-5876},
support = {tsqn202312391//Taishan Scholar Foundation of Shandong Province/ ; tsqn202408400//Taishan Scholar Foundation of Shandong Province/ ; 82501704//National Natural Science Foundation of China/ ; },
}

@article {pmid41761294,
year = {2026},
author = {Koo, BG and Seo, HE and Yun, Y and Kim, D and Kang, JM and Cho, J and Lee, SY and Lee, YJ and Park, KH and Lee, MJ and Noh, Y},
title = {Association of circulating proteasome activity with Alzheimer's pathology and cognitive functions in APOE ε4 carriers.},
journal = {Alzheimer's research & therapy},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13195-026-01994-w},
pmid = {41761294},
issn = {1758-9193},
support = {RS-2021-NR059245//the National Research Foundation (NRF) of Korea/ ; RS-2024-00332875//the Ministry of Health & Welfare and Ministry of Science and ICT, Republic of Korea/ ; HI14C1135//The Ministry of Health & Welfare, Republic of Korea/ ; RS-2024-00334574//The Ministry of Health & Welfare and Ministry of Science and ICT, Republic of Korea/ ; FRD2025-01//Gil Medical Center, Gachon University/ ; RS-2021-NR060117//Ministry of Education/ ; },
}

@article {pmid41761254,
year = {2026},
author = {Zameer, S and Anis, E and Sha, Q and Escobar Galvis, ML and Khan, S and Steiner, JA and Milčiūtė, M and Kerševičiūtė, I and Gabrielaite, M and Gordevicius, J and Pospisilik, A and Saiyed, N and Graham, SF and Brundin, P and Brundin, L},
title = {Genome-wide DNA methylation profiling in COVID-19 positive patients reveals alterations in pathways linked to neurological dysfunction.},
journal = {Clinical epigenetics},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13148-026-02094-0},
pmid = {41761254},
issn = {1868-7083},
abstract = {BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible RNA betacoronavirus, causing coronavirus disease-19 (COVID-19). Infection with SARS-CoV-2 can result in a broad spectrum of clinical outcomes, ranging from asymptomatic or mild to a severe, deadly illness. Emerging evidence suggests SARS-CoV-2 affects host gene regulation through epigenetic mechanisms, such as DNA methylation, potentially contributing to immune dysregulation and post-acute sequelae, including neurological and psychiatric disorders. However, the extent and functional relevance of these epigenetic changes remain uncertain.

METHODS AND RESULTS: We employed whole-genome methylation sequencing (WGMS) to profile DNA methylation in peripheral blood from SARS-CoV-2-positive patients across a spectrum of symptom severity, ranging from asymptomatic to severe (n = 101), in comparison to SARS-CoV-2-negative individuals (n = 105). We observed a widespread hypomethylation in the genomes of infected individuals, which was more pronounced in severe cases. Notably, we identified differentially methylated genes in patients with mild (19 genes), moderate (19 genes), and severe (35 genes) symptoms. These genes included those involved in canonical immune responses as well as known to be linked to neurodegenerative diseases. Subsequent pathway enrichment analysis further supported the significant association between the differentially methylated genes and those implicated in Alzheimer's and Parkinson's disease, as well as neuropsychiatric conditions, suggesting potential epigenetic links between acute SARS-CoV-2 infection and long-term neurological outcomes. Our WGMS comprehensively mapped severity-stratified genome-wide DNA methylation changes in COVID-19 patients.

CONCLUSION: Our findings underscore the potential importance of epigenetic regulation in the acute responses to SARS-CoV-2 infection and highlight an overlap with epigenetic mechanisms relevant for neuropsychiatric disease processes.},
}

@article {pmid41761230,
year = {2026},
author = {Hong, DK and Jeon, SH and Kang, M and Lee, S and Liu, X and Ahn, EH and Kang, SS},
title = {IL-18 binding protein attenuates neuroinflammation and cognitive decline in Alzheimer's disease.},
journal = {Journal of neuroinflammation},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12974-026-03720-7},
pmid = {41761230},
issn = {1742-2094},
support = {2022R1C1C1006166//National Research Foundation of Korea (NRF)/ ; R01-AG065517//National Institute of Health (NIH)/ ; },
}

@article {pmid41761178,
year = {2026},
author = {Torbidoni-Baldassari, B and Guazzarini, AG and Rezza, G and Bastiani, P and Cecchetti, R and Mecocci, P and Napolioni, V},
title = {The functional minisatellite at the 3'-UTR of SLC6A3/DAT1 and dementia spectrum disorders: an association study in a population of Central Italy.},
journal = {BMC medical genomics},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12920-026-02341-6},
pmid = {41761178},
issn = {1755-8794},
abstract = {BACKGROUND: Dementia comprises a spectrum of neurodegenerative disorders marked by progressive cognitive and behavioural decline, with Alzheimer's disease (AD) being the most prevalent form. While several genetic factors have been implicated in AD pathogenesis, a significant portion of heritability remains unexplained. One potential contributor to this "missing heritability" is structural variation within non-coding regions, such as variable-number tandem repeats (VNTRs). This study investigated the 40-bp VNTR located in the 3' untranslated region of the SLC6A3/DAT1 (henceforth referred to as DAT1) gene, a polymorphism previously associated with dopamine regulation and psychiatric conditions, for potential associations with dementia spectrum disorders and related neuropsychiatric phenotypes.

METHODS: A cohort of 799 elderly individuals from Central Italy, including AD, mild cognitive impairment (MCI), mixed dementia, and control subjects, was genotyped for the DAT1 VNTR and the APOE alleles. Neuropsychiatric evaluation was performed using the Neuropsychiatric Inventory (NPI).

RESULTS: No significant association was observed between DAT1-VNTR genotypes and any dementia diagnosis. However, neuropsychiatric analysis revealed significant associations between DAT1-VNTR genotypes and behavioural symptoms. Carriers of the short (*S) allele showed association with apathy (especially in the presence of APOE*4), irritability, and disinhibition. The *S/*S genotype was notably linked to elevated NPI scores for irritability and disinhibition.

CONCLUSIONS: These findings suggest that while the DAT1 VNTR is not directly associated with dementia diagnoses, it may contribute to modulating neuropsychiatric symptoms across dementia types. The results emphasize the importance of investigating non-coding genetic variants and their interactions with established risk alleles, such as APOE*4. Larger studies are needed to validate these findings and explore the functional consequences of DAT1 variation in neurodegeneration. This work contributes to our understanding of the dopaminergic system's influence on behavioural phenotypes in dementia. It warrants the VNTR as a candidate contributing to neuropsychiatric symptom variability in aging populations.},
}

@article {pmid41760995,
year = {2026},
author = {Zhang, B and Yu, X and Zhang, X},
title = {The evolving landscape of amyloid-targeting therapies in Alzheimer's disease: progress and challenges.},
journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology},
volume = {47},
number = {3},
pages = {},
pmid = {41760995},
issn = {1590-3478},
abstract = {BACKGROUND: Alzheimer's disease (AD) is the leading cause of dementia worldwide. Amyloid-β (Aβ) accumulation has long guided therapeutic development, though early β- and γ-secretase inhibitors failed to demonstrate clinical benefit.

METHODS: A narrative review was conducted based on a structured search of MEDLINE, Embase, and ClinicalTrials.gov, supplemented by manual screening of key reviews and Phase 3 trial reports on amyloid-targeting therapies.

RESULTS: Monoclonal antibodies including aducanumab, lecanemab, and donanemab achieve significant amyloid clearance and modest slowing of cognitive decline in Phase 3 trials, validating amyloid reduction as a disease-modifying pathway. However, clinical benefits are limited, amyloid-related imaging abnormalities (ARIA) remain safety concerns, and high costs restrict accessibility. Persistent therapeutic gaps reflect the multifactorial pathology of AD, including tau, neuroinflammation, and vascular dysfunction.

CONCLUSIONS: Amyloid-targeting therapies represent the first validated disease-modifying strategy for AD but are not definitive solutions. Future directions include earlier intervention, combination approaches, improved antibody design, and scalable biomarker implementation to enhance real-world impact.},
}

@article {pmid41760936,
year = {2026},
author = {Nigro, JT and Chatterjee, S and Freilich, S and Downs, M and Candib, A and Berron, E and Stein, TD and Zaia, J and Sethi, MK},
title = {Mass spectrometry analysis of young and aged mice and human Alzheimer's disease with Lewy body pathology using on-slide tissue digestion.},
journal = {Analytical and bioanalytical chemistry},
volume = {},
number = {},
pages = {},
pmid = {41760936},
issn = {1618-2650},
support = {A2020687F//BrightFocus Foundation Research Fellowship Award/ ; R01AG075876//National Institute of Aging/ ; 1UL1TR001430//Boston University Clinical Translational Science Institute Pilot Grant Award/ ; },
abstract = {Neurodegenerative disorders such as Alzheimer's disease (AD) and Lewy body disease (LBD) are typically diagnosed after irreversible pathology has developed. Aging, the strongest risk factor, drives molecular changes that predispose the brain to synaptic dysfunction and proteinopathy. Glycosylation and extracellular matrix (ECM) remodeling represent underexplored mechanisms linking aging to neurodegeneration, opening avenues for biomarker discovery, yet mass spectrometry-based glycoproteomics and glycomics studies remain limited. Here, we optimized an on-slide tissue digestion workflow for integrated glycome and proteome profiling from 5-mm brain regions from mice and humans using liquid chromatography data-independent acquisition-tandem mass spectrometry (LC-DIA-MS/MS). This workflow was applied to whole brains from age- and sex-stratified wild-type mice (n = 12) and to human postmortem prefrontal cortex tissue from individuals (n = 14) with brainstem- (n = 8) or limbic-predominant (n = 6) LBD, with or without AD co-pathology. DIA substantially increased protein, glycosylated protein, and ECM coverage by two- to threefold relative to traditional data-dependent acquisition (DDA), while library-free DIA searches further improved detection of low-abundance or region-specific proteins. In aged mouse brains, we observed increased levels of synapse-related proteins-including SYNPR, ZNT3, and HPCA-and enrichment of glutamatergic and postsynaptic pathways, reflecting age-associated synaptic remodeling. Glycomics revealed subtle shifts in the sulfation of chondroitin sulfate (CS) disaccharides with age. In human samples, AD-LBD brainstem tissue exhibited significantly reduced unsulfated, 4-O-sulfated, and total CS levels, along with differential expression of ECM, glycosylated, and mitochondrial proteins, and enrichment of mitochondrial pathways compared with LBD brainstem and AD-LBD limbic tissues. These findings indicate that AD co-pathology exerts a region-specific influence on the proteomic and glycomic landscape of LBD. Collectively, this study establishes a robust DIA-based on-slide digestion platform for high-resolution spatial glycomics and proteomics from minimal tissue, revealing aging- and pathology-specific molecular alterations relevant to neurodegeneration and providing a framework for biomarker discovery.},
}

@article {pmid41760935,
year = {2026},
author = {Son, A and Kim, H and Diedrich, JK and Bamberger, C and Wilkins, HM and Burns, JM and Morris, JK and Rissman, RA and Swerdlow, RH and Yates, JR},
title = {Structural signature of plasma proteins classifies the status of Alzheimer's disease.},
journal = {Nature aging},
volume = {},
number = {},
pages = {},
pmid = {41760935},
issn = {2662-8465},
support = {RF1AG061846-01//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; 5R01AG075862//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; P30-AG066530//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; P30AG072973//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; },
abstract = {Alzheimer's disease (AD) involves proteostasis dysregulation causing protein misfolding, but whether these structural changes manifest as plasma conformational biomarkers remains unclear. We profiled plasma protein structures from 520 participants including individuals with AD, individuals with mild cognitive impairment (MCI) and healthy controls. Using mass spectrometry and machine learning, we systematically characterized the structural proteome changes associated with ApoE variations and neuropsychiatric symptoms to identify AD-specific signatures. We developed a diagnostic panel using peptides from C1QA, CLUS and ApoB representing AD-associated structural changes. This three-marker panel achieved 83.44% accuracy in three-way classification (healthy versus MCI versus AD). Binary classification yielded area under the receiver operating characteristic curves of 0.9343 for healthy versus MCI and 0.9325 for MCI versus AD. Longitudinal samples were classified with 86.0% accuracy. This multi-marker panel based on plasma protein structural alterations represents a promising diagnostic approach that may enhance early AD detection and provide insights for clinical trials, improving therapeutic outcomes.},
}

@article {pmid41760895,
year = {2026},
author = {Li, J and Chen, M and Ren, P and Sun, G and Zhong, F and Zhu, Y and Li, G and Fan, Y and Chen, J and Xu, M and Qiao, M and Zhao, G and Xu, Y and Wu, W},
title = {Machine learning-guided Huanglian Jiedu decoction targets STING in periodontitis-induced Alzheimer's Disease.},
journal = {NPJ digital medicine},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41746-026-02468-x},
pmid = {41760895},
issn = {2398-6352},
support = {82174358//the National Natural Science Foundation of China/ ; },
abstract = {Alzheimer's disease (AD) is a progressive neurodegenerative disorder increasingly associated with peripheral inflammatory conditions such as chronic periodontitis (CP); however, the molecular mechanisms linking these conditions remain poorly understood. Here, we investigated the therapeutic effects of Huanglian Jieddu Decoction (HLJDD) on CP-induced AD using an integrative machine learning-guided multi-omics approach. Analysis of public single-cell RNA-sequencing data revealed pronounced inflammatory activation in microglia from AD samples. We further established a CP-induced AD rat model and performed hippocampal transcriptomic profiling. Multiple complementary machine learning strategies, including Random Forest-based feature selection, support vector machine-based refinement, network modeling, and interpretable model analysis, were applied to prioritize disease-relevant pathways from high-dimensional transcriptomic data. Across models, components of the cGAS-STING signaling pathway consistently exhibited strong and directional contributions to CP-AD pathology, indicating a central inflammatory axis linking peripheral infection to neurodegeneration. Guided by these data-driven insights, in vivo and in vitro experiments demonstrated that HLJDD suppressed cGAS-STING activation, attenuated neuroinflammation, and improved cognitive function in CP-induced AD models. Collectively, this study highlights the value of machine learning-assisted transcriptomic interpretation for mechanistic prioritization and identifies HLJDD as a multitarget therapeutic strategy for CP-induced AD.},
}

@article {pmid41760788,
year = {2026},
author = {Georgiou, A and Zanos, P and Onisiforou, A},
title = {Metformin provides superior neuroprotective potential compared to semaglutide in preventing diabetes-associated Alzheimer's disease via dual actions.},
journal = {Communications medicine},
volume = {},
number = {},
pages = {},
doi = {10.1038/s43856-026-01471-3},
pmid = {41760788},
issn = {2730-664X},
abstract = {BACKGROUND: Alzheimer's disease (AD) and Diabetes Mellitus Type II (DM2) share overlapping biological mechanisms, and diabetes increases the risk of developing AD. Treatments that modify the course of diabetes, such as metformin and semaglutide, have been proposed to protect the brain, but their effectiveness in preventing AD remains uncertain. This study aimed to systematically compare the potential of diabetes therapies to reduce the risk of AD.

METHODS: We developed an integrative framework combining comparative network pharmacology to evaluate 39 diabetes therapies in relation to AD. The analysis examined how each treatment influenced shared molecular pathways between the two conditions and measured their comparative impact score and validated key findings using gene expression data.

RESULTS: Here we show that metformin is the most promising therapy for protection against AD, while semaglutide ranks among the least effective, based on comparative analysis within the DM2-AD pathway-pathway comorbidity network. Metformin's effects are mediated through AMPK, insulin, and adipocytokine signaling, that influence key Alzheimer's-related processes. In contrast, semaglutide, despite its growing clinical prominence as a weight loss therapy, exhibits minimal engagement with core neurodegenerative pathways within the DM2-AD comorbidity network. Certain combination therapies, such as insulin glargine with lixisenatide and insulin degludec with liraglutide, display effects comparable to metformin.

CONCLUSIONS: These findings reveal that diabetes therapies differ in their ability to protect against AD. Metformin shows the strongest potential, supporting its prioritization for targeted studies in people with diabetes who are at high risk of AD, and highlighting the importance of precision medicine in future prevention trials.},
}

@article {pmid41760781,
year = {2026},
author = {Bruna-Jara, B and More, J and Lobos, P and Ponce, DP and Duran-Aniotz, C and Valdés, JL and Gleisner, MA and Tempio, F and Salech, F and Pizarro, M and SanMartín, CD and Cárcamo, M and Quest, AFG and López, M and Salazar-Onfray, F and Behrens, MI},
title = {Melanoma cell inoculation improves cognitive impairment in the 5xFAD mouse model of Alzheimer's disease.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-40699-w},
pmid = {41760781},
issn = {2045-2322},
support = {21210855//Agencia Nacional de Investigación y Desarrollo/ ; 3210806//Agencia Nacional de Investigación y Desarrollo/ ; 3240639//Agencia Nacional de Investigación y Desarrollo/ ; 1210622, ANID)/PIA/ANILLOS ACT210096//Agencia Nacional de Investigación y Desarrollo/ ; 11190882//Agencia Nacional de Investigación y Desarrollo/ ; 21221780//Agencia Nacional de Investigación y Desarrollo/ ; 1170925 and 1210644 CONICYT-FONDAP [15130011], FONDAP Continuation project [1523A0008]//Agencia Nacional de Investigación y Desarrollo/ ; 152220002//Agencia Nacional de Investigación y Desarrollo/ ; ICN09_16/ICN 2021_045//Agencia Nacional de Investigación y Desarrollo/ ; SEMILLA HCUCH (Hospital Clínico Universidad de Chile) 2022//Universidad de Chile/ ; U-Redes URC-036/17//Universidad de Chile/ ; 1190958 ID20I10252 and ID19I10302 URC-036/17//anid/ ; },
}

@article {pmid41760646,
year = {2026},
author = {Heo, S and Cha, M and Zhung, W and Kim, J and Keereewan, S and Cho, I and Park, M and Seo, W and Shin, H and Yoon, S and Ye, S and Heo, JK and Hwang, H and Kim, WY and Kim, Y and Han, S},
title = {Synthesis of 3-desoxycollinoketone B and its ability to reduce Alzheimer-associated misfolded proteins.},
journal = {Nature communications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41467-026-69662-z},
pmid = {41760646},
issn = {2041-1723},
support = {2021R1A2C2011203//National Research Foundation of Korea (NRF)/ ; 2018R1A5A1025208//National Research Foundation of Korea (NRF)/ ; KAIST Cross-Generation Collaborative Lab Project//KAIST (Korea Advanced Institute of Science and Technology)/ ; },
abstract = {Collinolactone, featuring a 7/10/6 tricyclic core, has been proposed to be biosynthesized via a transannular [6 + 4] cycloaddition reaction. Besides its intriguing architecture, collinolactone holds pharmaceutical promises due to its ability to disrupt amyloid-β (Aβ) and tau aggregation, which are specifically found as disease culprits in the brains of Alzheimer's disease (AD) patients and are key targets in current drug discovery efforts. However, challenges associated with its acquisition from a natural source and limited pharmacokinetic properties have hampered its further studies. Herein, we report the design, synthesis, and biological evaluation of 3-desoxycollinoketone B, a collinolactone derivative with improved pharmacokinetics for AD treatment. A stereoselective transannular [6 + 4] cycloaddition efficiently constructs the tricyclic core, allowing its scalable synthesis. AI-assisted binding prediction and simulations not only indicate superior binding of 3-desoxycollinoketone B to Aβ and tau aggregates to collinolactone, but also suggest a mechanistic basis for fibril destabilization. In vitro studies confirm its inhibition and dissociation of Aβ and tau fibrils, while in vivo experiments in AD mouse models show substantial amelioration of cognitive functions and Aβ/tau-associated pathology.},
}

@article {pmid41760587,
year = {2026},
author = {Li, H and Shi, C and Li, K and Fu, X and Lyu, Y and Xu, Y and Han, Y and Liang, W and Chuan, Q and Zhang, L},
title = {Chronic methanol exposure induces cognitive impairment and Alzheimer's-like pathology in rhesus monkeys.},
journal = {Animal models and experimental medicine},
volume = {},
number = {},
pages = {},
doi = {10.1002/ame2.70142},
pmid = {41760587},
issn = {2576-2095},
support = {2021-I2M-1-034//Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences/ ; 2023-PT180-01//Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences/ ; 2017-1001-07//PUMC Innovation Fund for Graduate Students/ ; 82161138027//National Natural Science Foundation of China/ ; },
abstract = {BACKGROUND: The absence of effective animal models for sporadic Alzheimer's disease (AD) remains a pivotal barrier to therapy development. Because methanol metabolism produces endogenous formaldehyde, a neurotoxic agent linked to cognitive decline, this study investigated whether chronic, low-dose methanol exposure could recapitulate AD-like pathology and cognitive deficits in rhesus monkey, thereby establishing a nonhuman primate animal model driven by this environmental-metabolic insult.

METHODS: Adult rhesus monkeys received low-concentration methanol for 9 months. Behavioral tests for cognition, locomotion, sleep, and vision were conducted. Postmortem analyses involved histopathological examination, immunohistochemistry, immunofluorescence, and Western blot to evaluate neuronal integrity, microglial activation, and the expression of key proteins associated with AD (amyloid-β [Aβ], phosphorylated tau, TAR DNA-binding protein 43 [TDP-43]) and cellular stress (synaptic markers, mitochondrial fission, autophagy, and apoptosis-related proteins).

RESULTS: Chronic methanol exposure led to progressive cognitive and memory impairment without significant motor or visual deficits. Neuropathology revealed brain atrophy, neuronal loss, synaptic damage, microglial activation, and mitochondrial structural disorganization. Critically, the exposed animals exhibited hallmark AD-like molecular alterations, including increased Aβ deposition, tau hyperphosphorylation, and TDP-43 dysregulation. Furthermore, neurotoxicity was associated with elevated urinary formaldehyde, enhanced mitochondrial fission, increased autophagy, and elevated apoptosis.

CONCLUSION: Chronic low-dose methanol exposure in rhesus monkeys recapitulates progressive cognitive deficits and AD-like neuropathological features. This model, driven by endogenous formaldehyde toxicity, effectively mimics key aspects of sporadic AD. Our findings shed light on the neurotoxic mechanisms of methanol and propose a reproducible and translationally relevant nonhuman primate model for studying AD pathogenesis and evaluating potential therapeutics.},
}

@article {pmid41760425,
year = {2026},
author = {Wang, Y and Anchipolovsky, S and Bhuiyan, P and Sato, L and Liang, G and Chuang, DM and Wei, H},
title = {Lithium chloride suppresses ferroptosis of induced pluripotent stem cells with ApoE4/E4 from a sporadic Alzheimer's disease patient.},
journal = {Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics},
volume = {},
number = {},
pages = {e00860},
doi = {10.1016/j.neurot.2026.e00860},
pmid = {41760425},
issn = {1878-7479},
abstract = {Alzheimer's disease (AD), particularly its sporadic form (SAD, 95 % AD patients), is strongly associated with the apolipoprotein E4 (ApoE4) genotype and characterized by oxidative stress, iron dysregulation, and increased susceptibility to ferroptosis. Lithium, a well-established neuroprotective agent, has shown potential to mitigate several pathological mechanisms in AD, including ferroptosis. This study investigates the therapeutic potential of lithium chloride in human induced pluripotent stem cells (iPSCs) derived from a SAD patient with ApoE4/E4 genotype and compared effects with those of isogenic gene-edited ApoE3/E3 control. Lithium treatment significantly improved cell viability in ApoE4/E4 iPSCs. It also reversed key ferroptosis phenotypes, including elevated cytosolic Fe[2+], increased expression of divalent metal transporter 1, reduced level of glutathione peroxidase 4, enhanced lipid peroxidation and excessive ROS production. Moreover, lithium (0.25 mM) normalized mitochondrial respiration and reduced proton leak, indicating preservation of mitochondrial function and protection against mitochondrial damage and cell death. Lithium also reduced the expression of type 1 InsP3 receptor (InsP3R-1) protein, a Ca[2+] channel located on the endoplasmic reticulum (ER) membrane. Together, these findings highlight lithium's inhibition of ferroptosis through modulation of iron metabolism, antioxidant defenses and inhibition of disrupted Ca[2+] signaling. Given the drug's demonstrated efficacy in reversing ApoE4-driven cellular vulnerabilities, lithium salt warrants further investigation for the treatment of AD.},
}

@article {pmid41760397,
year = {2026},
author = {Lin, YH and Hsu, TW and Kao, YC and Thompson, T and Carvalho, AF and Stubbs, B and Tseng, PT and Hsu, CW and Yang, FC and Tsai, CK and Yu, CL and Liang, CS and Tu, YK},
title = {Cumulative cognitive benefits and brain volume change with anti-amyloid therapies for Alzheimer's disease.},
journal = {Journal of neurology, neurosurgery, and psychiatry},
volume = {},
number = {},
pages = {},
doi = {10.1136/jnnp-2025-336691},
pmid = {41760397},
issn = {1468-330X},
abstract = {OBJECTIVE: This study aimed to evaluate the cumulative benefits of Food and Drug Administration (FDA)-approved monoclonal antibodies (mABs), administered at FDA-approved dosing regimens in slowing cognitive decline compared with placebo and acetylcholinesterase inhibitor (AChEI), and the dynamic relationships between cognitive decline, amyloid reduction and whole brain volume (WBV) changes in mAB treatment.

METHODS: Five major databases were systematically searched for double-blinded randomised controlled trials of patients with mild cognitive impairment due to Alzheimer's disease (AD) or mild AD treated with mAB or AChEI for at least 6 months. The primary outcomes were the change in cognitive function measured by Alzheimer's Disease Assessment Scale-cognitive subscale 14-Item (ADAS-Cog) and Clinical Dementia Rating Scale-Sum of Boxes (CDR-SOB). The secondary outcomes included amyloid burden and WBV changes.

RESULTS: There were 6479 participants across seven mAB trials, and 4993 participants in nine AChEI trials. Compared with placebo, the pooled percentage of cognitive slowing was 27.6% (95% CI 24.6% to 30.9%), and the pooled progression delay was 5.52 months over 19.5 months (1.40 to 9.65) on CDR-SOB in patients treated with mABs. For cognitive trajectories on ADAS-Cog, mAB progressively attenuated cognitive decline, whereas AChEI exhibited a smaller effect with large uncertainty and eventually provided no benefits. Additionally, the rates of cognitive decline and amyloid reduction stabilised over time, while WBV initially showed a rapid decline but progressively slowed. Finally, WBV decline was not associated with worsening cognitive function. Instead, a 1 cm³ reduction in WBV was linked to a 0.0975-point reduction in CDR-SOB (0.0614 to 0.1336).

CONCLUSIONS: In prodromal to mild AD, mAB therapy provided greater cumulative cognitive benefits than placebo and AChEI, and WBV reduction may reflect a treatment-related process rather than a detrimental sequela.

PROSPERO REGISTRATION NUMBER: CRD42024628107.},
}

@article {pmid41760325,
year = {2026},
author = {Tsai, PY and Lo, TS and Huang, JY and Yeh, CB and Lee, CY and Fan, YC and Yang, SF},
title = {The Impact of Insomnia on Dementia Risk in Hypertensive Individuals.},
journal = {In vivo (Athens, Greece)},
volume = {40},
number = {2},
pages = {1257-1268},
doi = {10.21873/invivo.14281},
pmid = {41760325},
issn = {1791-7549},
abstract = {BACKGROUND/AIM: Hypertension is a vascular disorder that affects both the vascular system and neural tissue. Insomnia may further impair health and contribute to dementia development. This study examined the association between insomnia and dementia in individuals with hypertension using a retrospective cohort design.

PATIENTS AND METHODS: Participants diagnosed with hypertension were classified into insomnia (n=97,751) and non-insomnia groups. Primary outcomes included Alzheimer's disease, vascular dementia, and Parkinson's disease. Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs).

RESULTS: During follow-up, the insomnia group included 759, 611, and 825 cases of Alzheimer disease, vascular dementia, and Parkinson disease, respectively, compared with 677, 499, and 546 cases in the non-insomnia group. Insomnia was significantly associated with higher risks of Alzheimer's disease (aHR=1.178, 95% confidence interval=1.062-1.307), vascular dementia (aHR=1.282, 95% confidence interval=1.139-1.443), and Parkinson's disease (aHR=1.582, 95% confidence interval=1.420-1.763). Cumulative incidences for all outcomes were also higher in the insomnia group. Sensitivity analyses showed elevated risks of Alzheimer's disease in middle-aged and older individuals with high hemoglobin A1c (HbA1c); increased vascular dementia risk in those of younger and older age, high low-density lipoprotein cholesterol, and elevated HbA1c; and higher Parkinson's disease risk among individuals with low high-density lipoprotein cholesterol, high low-density lipoprotein cholesterol, or elevated HbA1c.

CONCLUSION: Insomnia substantially increases dementia risk among individuals with hypertension, underscoring the clinical importance of sleep management in this population.},
}

@article {pmid41760205,
year = {2026},
author = {Yang, G and Zhu, C and Wu, J and Luo, K and Chen, X and Lin, J},
title = {[Early Alzheimer's disease recognition via multimodal hand movement quality assessment].},
journal = {Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi},
volume = {43},
number = {1},
pages = {70-78},
pmid = {41760205},
issn = {1001-5515},
abstract = {Alzheimer's disease (AD) is a common elderly illness, and the hand movement abilities of patients differ from those of normal individuals. Focusing on the utilization of RGB, optical flow, and hand skeleton as tri-modal image information for early AD recognition, a method for early AD recognition via multi-modal hand motion quality assessment (EADR) is proposed. First, a hybrid modality feature encoder incorporating global contextual information was designed to integrate the global contextual information of features from three specific modality branches. Subsequently, a fusion modality feature decoder network incorporating specific modality features was proposed to decode the overlooked information in the fusion modality branch from specific modality features, thereby enhancing feature fusion. Experiments demonstrated that EADR effectively could capture high-quality hand motion features and excelled in hand motion quality assessment tasks, outperforming existing models. Based on this, the action quality scoring regression model trained using the k-nearest neighbors algorithm demonstrated the best recognition performance for AD patients, with Spearman's rank correlation coefficient and Kendall's rank correlation coefficient reaching 90.98% and 83.44%, respectively. This indicates that the assessment of hand motor ability may serve as a potential auxiliary tool for early AD identification.},
}

@article {pmid41759988,
year = {2026},
author = {Yang, C and Qi, W and Li, W and Liang, F and Wang, H and Zhang, Y},
title = {Gut microbiota transmission induces cognitive impairment through amyloid pathology in wild-type mice.},
journal = {Neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.neuroscience.2026.02.041},
pmid = {41759988},
issn = {1873-7544},
abstract = {Alzheimer's disease (AD), the leading cause of dementia, is predominantly sporadic and influenced by non-genetic factors, including the gut microbiota. Cohabitation studies have shown microbial transmission between AD transgenic (Tg) and wild-type (WT) mice, leading to cognitive impairment; however, the mechanisms during early-life co-housing exposure remain largely undetermined. Here, one-month-old WT mice were housed with age-matched AD Tg (5XFAD) mice for 3 months. Gut microbiota composition was profiled by 16S rRNA sequencing, while brain amyloid-β 42 (Aβ42) levels were quantified by enzyme-linked immunosorbent assay (ELISA) and a nanoplasmonic sensor, respectively. Cognitive function was assessed by the Morris water maze and Barnes maze, and a probiotic intervention with Lactobacillus reuteri and Bifidobacterium pseudolongum was tested for therapeutic efficacy. WT mice co-housed with AD Tg mice (defined as ADWT) developed gut dysbiosis with microbial community shifts resembling those of AD Tg mice, accompanied by elevated brain Aβ42 and cognitive impairment. Finally, probiotic treatment reshaped gut microbial profiles and reduced cortical and hippocampal Aβ42 levels in ADWT mice. Together, these findings indicate that microbiota transfer through early-life co-housing induces gut dysbiosis, amyloid pathology, and cognitive deficits in WT mice, while targeted probiotic intervention mitigates these effects, supporting a microbiota-driven, non-genetic pathway in AD pathogenesis.},
}

@article {pmid41759954,
year = {2026},
author = {Wiskoski, HE and Mushtaq, R and Smith, S and Boehler, C and Zahra, S and Arias, JC and French, SR and Culwell, G and Do, L and Escareno, C and Heitkamp, E and Vazquez, F and Bedrick, EJ and Johnson, K and Altbach, M and Alexander, GE and Trouard, TP and Weinkauf, CC and , },
title = {CONTRAST INPUT AND MANUAL INTERVENTIONS SIGNIFICANTLY AFFECT FREESURFER MORPHOMETRY AND CLINICAL CORRELATIONS.},
journal = {NeuroImage},
volume = {},
number = {},
pages = {121831},
doi = {10.1016/j.neuroimage.2026.121831},
pmid = {41759954},
issn = {1095-9572},
abstract = {FreeSurfer is a widely used software for quantification of brain morphometrics in studies of neurodegeneration and aging. However, choice of input MRI contrast(s) and manual editing are variable across studies and their influence on clinically relevant outcomes remains unclear. Using non-demented, older-aged participant data from the Carotid and Mind study (CAM; N=123) and Alzheimer's Disease Neuroimaging Initiative (ADNI, N=143), FreeSurfer morphometrics from T1-MPRAGE, T1+T2-FLAIR, and T1+T2-SPACE were assessed with and without manual edits. In CAM and ADNI cohorts, input contrast significantly affected cortical thickness, surface area, and volume estimates across lobar regions. T1+T2-SPACE and T1+T2-FLAIR consistently produced greater cortical thickness estimates and smaller surface areas than T1-MPRAGE alone. These systematic differences altered the detection of expected age- and smoking-related associations to cortical thickness. Expert ratings indicated that T1-MPRAGE produced the highest baseline segmentation quality, while manual editing reliably improved this quality and reduced contrast-related morphometric biases across contrast types. These results suggest that choice of input contrast may introduce non-biological variation into FreeSurfer morphometrics, with T1-MPRAGE alone and manual editing yielding the most reliable outcomes. This indicates that careful consideration and reporting of post-processing protocols is critical for reproducibility and interpretation of morphometric outcomes across cohorts.},
}

@article {pmid41759830,
year = {2026},
author = {Cheng, B and Cheng, S and Wei, W and Pan, C and Wu, C and Zhang, F},
title = {Residential green space, natural environment, domestic garden, and the risk of Parkinson's disease: A prospective cohort study.},
journal = {Neurobiology of disease},
volume = {221},
number = {},
pages = {107334},
doi = {10.1016/j.nbd.2026.107334},
pmid = {41759830},
issn = {1095-953X},
abstract = {BACKGROUND: The relationship between residential greenness and the risk of neurodegenerative disorders, along with the role of genetic susceptibility, remains incompletely understood. This study aimed to examine the association between residential greenness and the incidence of neurodegenerative disorders.

METHODS: Using data from up to 220,000 participants with no prior neurodegenerative disorders at baseline, we utilized Cox proportional hazard model and restricted cubic spline regression to assess associations between residential greenness and the incidence of Parkinson's disease (PD), Alzheimer's disease (AD), and multiple sclerosis (MS). Stratified analyses were conducted by sex, age, body mass index, smoking, alcohol intake, polygenic risk scores, Townsend deprivation index, residential area type, and air pollution score.

RESULTS: Over a median follow-up of 10.8 years, 1211, 1054, and 411 participants developed PD, AD, and MS, respectively. Higher greenness was associated with reduced PD risk, especially 300-m buffer natural environment (HR = 0.537, [0.312, 0.92]) and 1000-m buffer green space (HR = 0.667, [0.458, 0.972]). Conversely, 300-m buffer green space was linked to increased AD risk (HR = 1.623, [1.007, 2.615]). Stratified analyses indicated stronger protective effects of natural environment against PD among older individuals and smokers. At both 300-m and 1000-m buffer green space, participants with high genetic susceptibility was linked to reduced PD risk. These benefits were more pronounced among socioeconomically disadvantaged individuals and those in highly air pollution areas.

CONCLUSION: Our findings suggest that different types and distance of exposure to residential greenness may exert varying influences on neurodegenerative disorders.},
}

@article {pmid41759740,
year = {2026},
author = {Zhang, JY and El Mammeri, N and Hong, M},
title = {Full-Length Tau Seeded by C-Shaped Tau Fibrils is Conformationally Variable.},
journal = {The Journal of biological chemistry},
volume = {},
number = {},
pages = {111315},
doi = {10.1016/j.jbc.2026.111315},
pmid = {41759740},
issn = {1083-351X},
abstract = {A number of neurodegenerative amyloid proteins have been found to adopt disease-specific structures in the human brain. This prion-like propagation of the amyloid structure requires recruitment of soluble monomers containing various posttranslational modifications to adopt the same structure as the fibril seeds. To understand the structural fidelity of seeding for amyloid proteins that possess large intrinsically disordered regions, here we investigate the seeding of a full-length phospho-mimetic tau protein, 4E tau, using a truncated tau construct that adopts the C-shaped Alzheimer's disease (AD) fold. Sedimentation gels indicate that four replicas of cross-seeded reactions all showed accelerated fibrillization kinetics. However, solid-state NMR spectra indicate that these cross-seeded samples have structurally variable cores, all of which differ from the AD fold of the seed fibrils, some of which resemble the unseeded triple-stranded structure of the full-length protein, and two of which contain two polymorphs. INEPT NMR spectra indicate that these cross-seeded replicas have similar dynamic disorder for their fuzzy coat, which differ from the dynamics of unseeded full-length 4E tau. These results indicate that accelerated fibrillization kinetics of tau does not necessarily correlate with faithful amplification of the seed structure, and surface-catalyzed nucleation of full-length tau with large intrinsically disordered regions leads to structural polymorphism and structural evolution from the seed fibrils.},
}

@article {pmid41759739,
year = {2026},
author = {Htet, M and Estay-Olmos, C and Hu, L and Wu, Y and Powers, BE and Campbell, CD and Rameshwar, A and Ahmed, MR and Hohman, TJ and Wang, Y and Schneider, JA and Bennett, DA and Menon, V and De Jager, PL and Kaas, GA and Colbran, RJ and Greer, CB},
title = {HEXIM1/P-TEFb complex controls RNA polymerase II pause release and immediate early gene induction following neuronal depolarization.},
journal = {The Journal of biological chemistry},
volume = {},
number = {},
pages = {111325},
doi = {10.1016/j.jbc.2026.111325},
pmid = {41759739},
issn = {1083-351X},
abstract = {Cognitive processes require de novo gene transcription in neurons. Memory requires the rapid and robust transcription of a class of genes called immediate early genes (IEGs). IEG transcription is facilitated by the formation of a poised basal state, in which RNA polymerase II (RNAP2) initiates transcription, but remains paused downstream of the promoter. Upon neuronal depolarization, the paused RNAP2 is released to complete the synthesis of messenger RNA (mRNA) transcripts, a process stimulated by positive transcription elongation factor b (P-TEFb). In many cell types, P-TEFb is sequestered into a large inactive complex containing Hexamethylene bisacetamide inducible 1 (HEXIM1), but the impact of this interaction on neuronal gene transcription is not yet fully understood. In this study, we found that neuronal expression levels of HEXIM1 mRNA are highly correlated with impaired cognition in Alzheimer's disease. It is also induced in the hippocampus during memory formation, and following depolarization in neurons. The role of HEXIM1 in neuronal gene transcription was then explored in murine neuronal cultures where we found that calcium frees P-TEFb from the HEXIM1 inhibitory complex. Modulation of P-TEFb by inhibiting the activity of the cyclin-dependent kinase 9 (CDK9) subunit of this complex significantly impacts IEG induction, particularly during repeated depolarization. Our findings indicate that HEXIM1 in complex with P-TEFb plays an important role in establishing and resetting the poised RNAP2 state, enabling efficient activation of genes necessary for synaptic plasticity.},
}

@article {pmid41759511,
year = {2026},
author = {Chen, X and Holtzman, DM and Colonna, M},
title = {Immunity in Alzheimer's disease: From mechanisms to therapies.},
journal = {Immunity},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.immuni.2026.02.004},
pmid = {41759511},
issn = {1097-4180},
abstract = {Alzheimer's disease (AD) is a progressive neurodegenerative disorder that leads to cognitive decline, dementia, and ultimately death. Recent anatomical and functional discoveries of neuroimmune interactions during the development and progression of AD are beginning to shed light on disease mechanisms and potential precision immunotherapies. Here, we review the current understanding of the contribution of innate and adaptive immunity to AD pathogenesis and progression. We discuss how microglia and T cells shape stage-specific immune responses in AD, how genetic risk converges on microglial activation and antigen presentation pathways, and the protective and pathogenic roles of microglia and T cells during distinct stages of AD progression. In the context of this deeper understanding of immune cells in AD, we discuss emerging therapeutic approaches in the clinic and argue for the importance of interventions that precisely modulate neuroimmune dynamics at different stages of AD.},
}

@article {pmid41759439,
year = {2026},
author = {Paul, S and Verma, J and Mehan, S},
title = {Oxytocin beyond social bonding: Advancing neuromodulation, synaptic plasticity, and epigenetic precision in CNS disorders.},
journal = {Neuropeptides},
volume = {116},
number = {},
pages = {102597},
doi = {10.1016/j.npep.2026.102597},
pmid = {41759439},
issn = {1532-2785},
abstract = {Oxytocin, a neuropeptide predominantly produced in the hypothalamus, has garnered significant attention for its multifaceted roles extending beyond social bonding and reproduction to therapeutic applications in neurodegenerative and neuropsychiatric disorders. This review explores oxytocin's neuroprotective properties, including anti-inflammatory, antioxidant and anti-apoptotic effects, which counteract pathological mechanisms underlying diseases like Alzheimer's, Parkinson's and Epilepsy. Oxytocin's ability to modulate key neurotransmitter systems GABAergic, dopaminergic, and serotonergic pathways enhances synaptic plasticity, neurogenesis, and emotional regulation. These mechanisms have positioned oxytocin as a promising intervention for neuropsychiatric conditions such as autism, schizophrenia, depression, and anxiety. Preclinical and clinical studies have shown that intranasal administration of oxytocin improves social cognition, reduces symptom severity, and is well-tolerated, though challenges remain in standardizing dosages and measuring oxytocin levels due to individual variability. Emerging technologies, such as nanoparticle-based drug delivery systems, offer solutions to enhance oxytocin's bioavailability and brain penetration, making targeted, patient-specific therapies feasible. Epigenetic modifications of the oxytocin receptor gene including DNA methylation have been associated with variability in social and stress-related behaviors. While these findings offer insight into inter-individual differences, their application to precision medicine remains speculative and will require rigorous clinical validation. Combination therapies, integrating oxytocin with agents targeting neuroinflammation and synaptic plasticity, hold potential for synergistic effects. Despite methodological and translational challenges, oxytocin represents a transformative therapeutic agent with broad applications across neurological, psychiatric, and systemic disorders. Future research focusing on nanotechnology, epigenetics, and long-term clinical trials will be pivotal in realizing the full potential of oxytocin-based interventions for complex, multifactorial diseases.},
}

@article {pmid41759393,
year = {2026},
author = {Akaike, S and Shinpo, K and Nakagawa, Y and Otsuki, M},
title = {A case of autotopagnosia in Alzheimer's disease: Mechanistic insights into body-part localization.},
journal = {Cortex; a journal devoted to the study of the nervous system and behavior},
volume = {197},
number = {},
pages = {181-192},
doi = {10.1016/j.cortex.2026.02.007},
pmid = {41759393},
issn = {1973-8102},
abstract = {Autotopagnosia is a rare neuropsychological syndrome characterized by disordered localization of body parts. Reports remain scarce and the cognitive mechanisms underlying this syndrome are not fully understood. We describe the case of a 65-year-old Japanese man whose clinical and neuropsychological profiles and neuroimaging findings supported a diagnosis of probable Alzheimer's disease. Notably, he had episodic memory deficits and visuospatial impairment without aphasia, along with Gerstmann syndrome and marked autotopagnosia. Neuropsychological examinations assessed body-part knowledge and processing, combining pictorial representations, spoken instructions, and tactile input with pointing and naming responses; single-case comparisons were benchmarked against age-matched, cognitively healthy adults (n = 20). The patient could name body parts and retain general knowledge and visual recognition of them, yet consistently failed to localize those parts on whole-body stimuli: his own body, another person's body, and a full-body diagram. Language-only probes of inter-part spatial relations were impaired, whereas non-spatial definitions were preserved. This cross-modal profile is not attributable to a single sensory modality or language/motor factor, nor is it readily explained by accounts invoking failures to map visual/somatosensory inputs to body-part location or the primary disruption of an egocentric, multisensory body schema. Instead, it is most consistent with a modality-independent disruption of body-part localization knowledge, i.e., a high-level body-centered spatial map linking body-part labels to their canonical positions on the human body. Our findings suggest that autotopagnosia can be parsimoniously unified through this mechanism. These observations underscore the need for standardized, modality-diverse examinations to clarify the mechanisms underlying this rare clinical phenomenon.},
}

@article {pmid41759353,
year = {2026},
author = {Kuring, JK and Mathias, JL and Ward, L and Tachas, G},
title = {Inflammatory markers associated with dementia: a systematic review and meta-analysis.},
journal = {Journal of psychiatric research},
volume = {197},
number = {},
pages = {26-40},
doi = {10.1016/j.jpsychires.2026.02.044},
pmid = {41759353},
issn = {1879-1379},
abstract = {BACKGROUND: Dementia has been linked to several modifiable risk factors, including mental illness. The inflammatory-mediated neurodegeneration hypothesis posits a causal relationship between the two whereby mental illness triggers an inflammatory response, which in turn acts as a catalyst for the neurodegenerative changes that lead to dementia. Existing meta-analyses have yet to investigate inflammatory markers in Alzheimer's disease (AD), vascular dementia (VaD), dementia with Lewy bodies (DLB), or fronto-temporal dementia (FTD) in the context of the inflammatory-mediated neurodegeneration hypothesis. This meta-analysis therefore explored whether a) AD, VaD, DLB, and FTD are each associated with greater inflammation than healthy controls, independent of comorbid mental or physical health problems with a known inflammatory response, and b) there are any similarities in the inflammatory profiles associated with these dementia subtypes.

METHODS: PubMed, EMBASE, PsycINFO and CINAHL searches identified 41 eligible studies.

RESULTS: AD is associated with an inflammatory response, with tentative evidence to indicate that VaD, DLB, and FTD are also associated with inflammation. However, the inflammatory response appears to differ across these conditions.

LIMITATIONS: The data for VaD, DLB, FTD and a number of inflammatory markers were limited.

CONCLUSIONS: Although tentative, AD, VaD, DLB, and FTD appear to be associated with discrete inflammatory processes that are not attributable to other common comorbid mental or physical health problems that cause inflammation. Whether this inflammatory response plays a causal role in the development of dementia and/or is triggered by prior mental illness remains to be determined.},
}

@article {pmid41759303,
year = {2026},
author = {Argenti, L and Massa, F and Losa, M and Lombardo, L and Lorenzini, L and Peira, E and Sofia, L and Raffa, S and Sambuceti, G and Garbarino, S and Kreshpa, W and Bozzo, G and Pelagotti, V and Pulze, M and Gualco, L and Hamedani, M and Cirone, A and Francia, S and Brugnolo, A and Girtler, N and Caneva, S and Roccatagliata, L and Mattioli, P and Morbelli, S and Ali, S and Piana, M and Serrati, C and Uccelli, A and Chincarini, A and Arnaldi, D and Orso, B and Pardini, M},
title = {Neurotransmitter landscape and neurodegeneration patterns in Alzheimer's Disease.},
journal = {Neurobiology of aging},
volume = {162},
number = {},
pages = {49-56},
doi = {10.1016/j.neurobiolaging.2026.02.004},
pmid = {41759303},
issn = {1558-1497},
abstract = {Alterations of neurotransmitter systems in Alzheimer's Disease (AD) remain partially understood, mainly due to the complexity of simultaneously and directly assessing these systems in vivo. To address this knowledge gap, recent approaches have been proposed correlating normative multi-tracer neurotransmitter data with established disease biomarkers, including [[18]F]FDG-PET. We retrospectively enrolled 90 AD patients (72.8 ± 7 years, Mini Mental State Examination - MMSE 24 ± 4.1) and 42 Healthy Controls (HC, 70 ± 8.5 years, MMSE 29 ± 0.8), all with a brain [[18]F]FDG-PET scan and MMSE collected at baseline. All AD diagnoses were confirmed by a positive amyloid marker (CSF or Amyloid PET). We performed a voxel-based analysis between AD and HC to explore brain relative hypometabolism and then, using the established JuSpace toolbox, we explored the spatial correlation between brain hypometabolism and PET-maps targeting glutamate (mGluR5), GABA (GABA-a), dopamine (D1, D2, FDOPA), serotonin (SERT, 5HT1a, 5HT1b, 5HT2a, 5HT4), noradrenaline (NAT) and choline (VAChT) systems. The significant results obtained were then correlated with MMSE and cortical amyloid burden, measured with Amyloid PET. The distribution of brain relative hypometabolism of AD patients was spatially associated with maps of 5HT2a and mGluR5 distribution (both p = 0.02, r = -0.11). Both 5HT2a and mGluR5 regional relative distribution correlated with a lower MMSE, 5HT2a was also associated with a greater cerebral amyloid burden. These findings are consistent with recent multimodal imaging studies and suggest that serotonergic and glutamatergic receptor-dense regions may show preferential metabolic vulnerability in AD, with relevance for cognitive impairment.},
}

@article {pmid41758970,
year = {2026},
author = {Raskatov, JA},
title = {Amyloid Alpha: The Neglected Cousin of Amyloid Beta.},
journal = {Chembiochem : a European journal of chemical biology},
volume = {27},
number = {5},
pages = {e202500912},
doi = {10.1002/cbic.202500912},
pmid = {41758970},
issn = {1439-7633},
support = {R01AG074954/AG/NIA NIH HHS/United States ; },
abstract = {For decades, amyloid β (Aβ) has been the principal therapeutic target for therapies of Alzheimer's disease (AD). An alternative processing product, known as P3, may form if the amyloid precursor protein is cleaved by α-secretase instead of β-secretase. This shorter peptide has received little attention and is often dismissed as nonamyloidogenic and nontoxic. Our research, and that of others, has shown that the shorter peptide is anything but innocuous. We demonstrated that P3-or Amyloid α (Aα) as we termed it-readily forms oligomers and fibrils and is itself potentially neurotoxic and may interact with Aβ to modulate the aggregation behavior and toxicity of Aβ. This perspective article provides a succinct overview of current uncertainties around P3/Aα. A revision of the amyloid cascade hypothesis to include P3/Aα is urgently needed. This peptide is, most likely, not an innocent bystander, but a distinct aggregating peptide that is itself potentially neurotoxic and may be contributing to AD.},
}

@article {pmid41758766,
year = {2026},
author = {Flavell, J and Ahern, EGM and Logan, B and Shaw, TB and Adam, RJ and McElligott, CAT and Nestor, PJ},
title = {Differentiating behavioural presentations of biomarker-confirmed Alzheimer's disease from frontotemporal lobar degeneration using the Addenbrooke's Cognitive Examination-III.},
journal = {Dementia and geriatric cognitive disorders},
volume = {},
number = {},
pages = {1-17},
doi = {10.1159/000551258},
pmid = {41758766},
issn = {1421-9824},
abstract = {INTRODUCTION: Differentiating frontotemporal lobar degeneration (FTLD) from Alzheimer's disease (AD), particularly when presenting with overlapping behavioural symptoms, remains clinically challenging. This study assessed the utility of Addenbrooke's Cognitive Examination-III (ACE-III)-derived ratios in distinguishing these conditions.

METHODS: A retrospective cohort of 115 patients (n=52 biomarker-confirmed AD, n=63 FTLD) with overlapping behavioural symptoms was analysed. ACE-III scores and behavioural profiles were examined, and novel ratios were tested.

RESULTS: The novel Phonemic Fluency/Orientation-Memory (PFOM) ratio outperformed existing ACE-III metrics, achieving an area under the curve (AUC) of 0.85 (sensitivity 84.1%, specificity 73.1%) for differentiating FTLD from AD. Notably, longer symptom duration in AD, but not in FTLD, was associated with worsening frontal and cognitive symptoms. Patients with AD were significantly older than those with FTLD.

DISCUSSION: These novel ratios showed robust diagnostic performance, regardless of disease duration, and better reflects FTLD's cognitive profile. It may offer improved clinical utility over traditional ACE-III measures.},
}

@article {pmid41758499,
year = {2026},
author = {Hacil, A and Piccoli, M and Antakly-Hanon, Y and Guglieri, M and Lochon, L and Duneton, S and Hanon, O and Fauchier, L},
title = {Association of SGLT2 inhibitors and new-onset dementia in non-diabetic patients with heart failure.},
journal = {European journal of heart failure},
volume = {},
number = {},
pages = {},
doi = {10.1093/ejhf/xuag038},
pmid = {41758499},
issn = {1879-0844},
abstract = {AIMS: Patients with heart failure (HF) are at increased risk of developing dementia, an outcome that substantially worsens clinical prognosis and quality of life. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are well-established in cardiovascular protection, but their association with incident dementia remains poorly documented, particularly in non-diabetic populations.

METHODS: We conducted a retrospective cohort study using the TriNetX Research Network (2016-2025), including adults with HF and no prior history of dementia or diabetes. Patients initiating SGLT2i (n = 46 049) were compared with non-users (n = 205 010). After 1:1 propensity score matching, 39 979 pairs were analysed. The primary outcome was new-onset dementia. Secondary outcomes were Alzheimer's disease, vascular dementia, and all-cause mortality. Additional cardiovascular outcomes included ischaemic stroke, myocardial infarction, and end-stage kidney disease (ESKD). Outcomes were assessed using Kaplan-Meier survival analysis and Cox proportional hazards models.

RESULTS: Over a relatively short median follow-up of 1.2 years in a population with a mean age of 64 years, SGLT2i use was associated with a significantly lower risk of new-onset dementia [hazard ratio (HR) 0.77, 95% confidence interval (CI) 0.68-0.87; P < .001]. Risks were also reduced for Alzheimer's disease (HR 0.58, 95% CI 0.45-0.74; P < .001), vascular dementia (HR 0.41, 95% CI 0.27-0.62; P < .001), and all-cause mortality (HR 0.63, 95% CI 0.61-0.66; P < .001). SGLT2i therapy was further associated with lower risks of ischaemic stroke (HR 0.67, 95% CI 0.60-0.75; P < .001) and ESKD (HR 0.75, 95% CI 0.63-0.89; P = .001).

CONCLUSION: In this large, real-world patient with HF without diabetes, SGLT2i therapy was associated with a significantly lower risk of new-onset dementia and all-cause mortality.},
}

@article {pmid41758465,
year = {2026},
author = {Gönüllü, S and Aydın, Ş and Çelik, H and Çelik, O and Küçükler, S and Topal, A and Akay, R and Yıldız, MO and Alım, B and Özdemir, S},
title = {Therapeutic Effects of miR-21-5p-Enriched Milk Extracellular Vesicles on Alzheimer's Disease-Associated Neurotoxicity in Vitro.},
journal = {Cell biochemistry and biophysics},
volume = {},
number = {},
pages = {},
pmid = {41758465},
issn = {1559-0283},
}

@article {pmid41758357,
year = {2026},
author = {},
title = {Correction to: Diagnostic Value of Serum p-tau217 in Alzheimer Disease: Equal to Plasma in Levels and Clinical Utility?.},
journal = {Clinical chemistry},
volume = {},
number = {},
pages = {},
doi = {10.1093/clinchem/hvag015},
pmid = {41758357},
issn = {1530-8561},
}

@article {pmid41758343,
year = {2026},
author = {Riedel, EO and Schramm, S and Bongratz, F and Gruber, MJ and Sepp, D and Paprottka, KJ and Zimmer, C and Wiestler, B and Hedderich, DM},
title = {Deep learning-based synthetic brain MRI for the assessment of regional atrophy patterns in neurodegenerative diseases.},
journal = {European radiology},
volume = {},
number = {},
pages = {},
pmid = {41758343},
issn = {1432-1084},
support = {TUM KKF Clinician Scientist Program, project reference E-19 and H-27//Faculty of Medicine, Munich University of Technology/ ; },
abstract = {OBJECTIVES: Assessing regional brain atrophy on 3D-T1w imaging is crucial for evaluating neurodegenerative disorders. However, high-quality volumetric imaging is not always available. Thus, AI-based algorithms were developed to generate "synthetic" 3D-T1w sequences using various clinical sequences as input. This retrospective study aims to investigate whether regional atrophy patterns are preserved in deep learning-based synthetic 3D-T1w sequences from different inputs.

MATERIALS AND METHODS: The study included patients with Alzheimer's disease (AD), Frontotemporal dementia (FTD), and healthy controls (HC). Probands were scanned at 3 T, and deep learning-based synthetic 3D-T1w images were generated from various inputs (3D FLAIR, 4 mm axial FLAIR, 4 mm coronal T2) using FreeSurfer-based SynthSR. Real 3D-T1w images served as the reference standard. Brain volumetry was performed using SynthSeg+ in FreeSurfer and the AssemblyNet-AD-FTD pipeline in VolBrain.

RESULTS: Global and regional volumes differed significantly between deep learning-based synthetized sequences and the reference standard 3D T1 for all subgroups and inputs (total white matter volume AD p = 0.0002, FTD p < 0.0001, HC p = 0.0116; total gray matter volume for AD, FTD, and HC p < 0.0001), except for hippocampal volumes. This systematic error in overestimating volumes affected automated disease probability prediction in FTD for all inputs (p < 0.0001) and in HC for coronal T2 input (adj. p = 0.0054).

CONCLUSION: Deep learning-based synthetic 3D-T1w sequences introduce systematic errors in assessing global and regional brain volumetric measures, leading to overestimated volumes in controls and patients. Resulting synthetic images should be used cautiously, especially for volumetric analyses.

KEY POINTS: Question It remains unclear whether deep learning-based synthetic 3D-T1w images from various inputs preserve regional atrophy patterns sufficiently to serve as input for automated volumetry. Findings Deep learning-based synthetic T1w images overestimate regional and global brain volumes in neurodegenerative diseases and controls, increasing with lower quality inputs. Clinical relevance Deep learning-based synthetic images should only be used with caution for volumetric evaluation of brain MRI scans. If possible, 3D scans should be used as input.},
}

@article {pmid41758277,
year = {2026},
author = {Cárdenas Sánchez, M and Orozco Valero, A and García, JM and Rodríguez-González, V and Montobbio, N and Pelayo, F and Morillas, C and Poza, J and Gómez, C and Martínez-Cañada, P},
title = {A Framework Integrating Spiking Cortical Circuit Modeling and Simulation-Based Inference to Probe Biomarkers of Cortical Dysfunction in Alzheimer's Disease.},
journal = {Interdisciplinary sciences, computational life sciences},
volume = {},
number = {},
pages = {},
pmid = {41758277},
issn = {1867-1462},
abstract = {Understanding circuit-level imbalances in the cortex can yield mechanistic insights into Alzheimer's disease (AD), supporting both diagnosis and therapeutic development. We present a computational framework that integrates the causal interpretability of mechanistic modeling with the predictive power of simulation-based inference (SBI) to identify candidate neuroimaging biomarkers of cortical circuit dysfunction in AD. Using a spiking cortical circuit model with recurrent excitatory and inhibitory populations, we generated a comprehensive dataset of two million simulations and produced realistic electroencephalography (EEG) signals through biophysically grounded causal filtering of spiking activity. From these signals, we extracted EEG features serving as potential biomarkers of cortical dysregulation and trained SBI models optimized for accuracy and efficiency. Comparisons across feature sets revealed that multi-feature SBI models achieved higher inference accuracy than single-feature approaches in predicting various cortical parameters, suggesting that no single biomarker is sufficient to fully characterize the neural processes underlying the EEG signal. Applying the best-performing models to real EEG data from AD patients at varying stages uncovered distinct patterns of cortical dysfunction, including a progressive reduction in cortico-cortical connectivity, linked to the accelerated breakdown of synaptic connections widely reported in AD progression. A reduction in the efficacy of the excitatory time constant was also observed, likely reflecting a shift in the excitation/inhibition (E/I) balance toward inhibition in later stages of the disease. Our framework provides a scalable and interpretable bridge between local-scale mechanistic brain modeling and clinical neuroimaging, advancing the identification of physiologically meaningful biomarkers of cortical dysfunction in AD.},
}

@article {pmid41758263,
year = {2026},
author = {Movaffagh, S and Behzadifard, M and Moghaddasi, M and Nazarinia, D and Jafaripour, L},
title = {Kinetin mitigate neurodegenerative damage of Alzheimer induced by beta-amyloid in male rats by antioxidant and antithrombotic effects.},
journal = {Metabolic brain disease},
volume = {41},
number = {1},
pages = {},
pmid = {41758263},
issn = {1573-7365},
}

@article {pmid41758187,
year = {2026},
author = {Orlenko, A and Li, B and Khanjani, N and Venkatesan, M and Shen, L and Ritchie, MD and Wang, ZP and Obafemi-Ajayi, T and Moore, JH},
title = {A random-walk-based learning framework to uncover novel gene candidates for Alzheimer's disease therapy.},
journal = {Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing},
volume = {31},
number = {},
pages = {815-829},
doi = {10.1142/9789819824755_0059},
pmid = {41758187},
issn = {2335-6936},
abstract = {Identifying repurposable therapeutic targets for Alzheimer's disease (AD) remains challenging due to various clinical and biological factors. This study aimed to identify candidate genes for AD therapy. We hypothesize that gene and disease-specific network properties-learnable from these large-scale biomedical knowledge graphs-can inform implicit gene-AD connections and prioritize repurposable AD drug targets. To evaluate the hypothesis, we focused on druggable genes curated from Drug-Gene Interaction Database and Alzheimer's Knowledge Base (AlzKB). We applied scalable random walk methods to Hetionet to learn unbiased gene and disease embeddings, representative of their topological and semantic network properties. The embeddings were then used to compute gene-AD similarity and derive network-based scores for each gene. To validate the scores, using Alzheimer's Disease Sequencing Project (ADSP) data, we constructed AD classifier models with Tree-based pipeline optimizer 2 (TPOT2), an automated machine learning framework. Models were optimized for performance, model complexity, and high aggregate network-based scores. Network-based scores successfully prioritized diverse feature sets-many not previously associated with AD-that are enriched in biologically meaningful body parts such as brain, and pathways including neuronal signaling, potassium channels, and creatine metabolism. The results suggested that knowledge graphs and network-informed embeddings can capture both known and novel insights into AD mechanisms. Additionally, integrating networkbased scores with feature-set-guided TPOT2 offers a scalable and biologically interpretable framework for AD drug repurposing and discovery.},
}

@article {pmid41758175,
year = {2026},
author = {Rifat, JM and Tabashum, T and Rahman, MM and Mokter, MF and Engala, S and Bozdag, S},
title = {BioLM-NET: an interpretable deep learning model combining prior biological knowledge and contextual LLM gene embeddings on multi-omics data to predict disease.},
journal = {Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing},
volume = {31},
number = {},
pages = {644-663},
doi = {10.1142/9789819824755_0047},
pmid = {41758175},
issn = {2335-6936},
abstract = {Biologically informed deep neural networks, which connect input layer to hidden layers based on genepathway relationship have gained popularity in recent years. However, most existing methods do not incorporate protein-protein interactions (PPI) and protein-DNA interactions (PDI) in their designs. In this study, we introduce BioLM-NET, a deep learning-based framework that fuses single cell or bulk gene expression data and DNA methylation data with prior biological knowledge including Protein- Protein Interactions (PPI), Protein-DNA Interactions (PDI). BioLM-NET also aggregates latent representation of omics signals at pathway-level through an attention-based pathway layer where a pretrained large language model (LLM) was incorporated to generate context-specific gene embeddings. We evaluated BioLM-NET on single cell colorectal cancer data from scTrioseq2 platform to predict primary and metastatic cancer cells, on TCGA-BRCA, TCGA-GBM, TCGA-COAD to predict cancer subtypes and ROSMAP data to predict Alzheimer's disease patient. Our results showed that BioLMNET outperformed baseline and state-of-the-art (SOTA) methods, P-NET and PASNet with statistical significance on scTrioseq2 data, TCGA-COAD and ROSMAP data and ties with SVM and Dense neural network on TCGA-BRCA data. Our ablation studies demonstrated the importance of incorporating PPI, PDI data and attention-based pathway layer. We also interpret our models and found out that our important input features are significantly enriched in GO terms and KEGG pathways and can serve as potential biomarkers or therapeutic targets for the corresponding disease.},
}

@article {pmid41758152,
year = {2026},
author = {Pugh, S and Hill, M and Hwang, S and Wu, R and Jang, K and Iannone, S and O'Connor, K and O'Brien, K and Eaton, E and Johnson, K},
title = {WATCH-SS: Developing a Trustworthy and Explainable Modular Framework for Detecting Cognitive Impairment from Spontaneous Speech.},
journal = {Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing},
volume = {31},
number = {},
pages = {338-353},
doi = {10.1142/9789819824755_0024},
pmid = {41758152},
issn = {2335-6936},
abstract = {Early detection of cognitive impairment (CI) is critical for timely intervention in Alzheimer's disease and AD-related dementias. To address this, we propose the Warning Assessment and Alerting Tool for Cognitive Health from Spontaneous Speech (WATCH-SS), a modular and explainable three-stage framework for detecting CI from a patient's speech sample. The framework uses detectors for five linguistic and acoustic indicators of CI, aggregates their outputs into a set of clinically interpretable summary features, and uses a predictive model for CI classification. We consider multiple approaches to implementing these detectors that range from simple, computationally efficient methods suitable for real-time analysis to strong, resource-intensive methods, better for high accuracy offline analysis. On the DementiaBank ADReSS dataset, WATCH-SS achieved strong predictive performance (AUC = 80% on the test set). This work demonstrates that a modular, feature-based approach can achieve strong performance while providing a transparent diagnostic profile, representing a significant step towards a trustworthy and clinically-usable screening tool for primary care.},
}

@article {pmid41758127,
year = {2026},
author = {Ueda, M and Suzuki, T and Yoshimizu, T and Konuma, T and Maekawa, M and Sasase, T and , and Nishiu, J},
title = {Cerebral glucose uptake and cognitive functions: A phenome-wide Mendelian randomization study.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261418310},
doi = {10.1177/13872877261418310},
pmid = {41758127},
issn = {1875-8908},
abstract = {BackgroundBased on both physiological perspectives and observational findings, increasing cerebral glucose uptake appears to be a novel therapeutic strategy to preserve cognitive function in patients with Alzheimer's disease (AD). However, the inherent limitations of observational studies make it difficult to establish clear causality.ObjectiveTo evaluate the potential of cerebral glucose uptake as a novel therapeutic strategy for AD through a systematic investigation of its causal relationship with cognitive function.MethodsThe [[18]F] fluoro-2-deoxy-2-D-glucose positron emission tomography (FDG-PET) was used as an indicator of cerebral glucose uptake. Phenome-wide Mendelian randomization was performed to investigate the causal relationships between glucose uptake across 113 brain regions and 96 cognitive assessment scores using data from the Alzheimer's Disease Neuroimaging Initiative.ResultsIn the primary analysis, employing the inverse-variance weighted method, genetically predicted increases in cerebral glucose uptake exhibited a consistent trend toward beneficial changes in cognitive assessment scores across brain regions independent of brain volume. Subsequent sensitivity analyses, horizontal pleiotropy assessments and corrections for multiple testing demonstrated robust causal relationships between cerebral glucose uptakes and cognitive assessment scores, including the Alzheimer's Disease Assessment Scale and the Clinical Dementia Rating, across multiple brain regions.ConclusionsThis study provides genetic evidence suggesting causal relationship between cerebral glucose uptake and cognitive function. These findings indicate that FDG-PET images in specific brain regions may serve as a surrogate marker for cognitive function and support the potential of therapeutic strategies targeting cerebral glucose uptake to preserve cognitive function in patients with AD.},
}

@article {pmid41758045,
year = {2026},
author = {Martináková, L and Chmátalová, Z and Veverová, K and Jurášová, V and Katonová, A and Laczó, M and Laczó, J and Vyhnálek, M and Hort, J and Skoumalová, A},
title = {Specific Lipid Peroxidation Products in Erythrocytes and Their Relationship to the Pathogenesis of Alzheimer's Disease.},
journal = {Journal of cellular and molecular medicine},
volume = {30},
number = {5},
pages = {e70990},
pmid = {41758045},
issn = {1582-4934},
support = {180221//Grantová Agentura, Univerzita Karlova/ ; LX22NPO5107//NextGenerationEU/ ; FNM,00064203//Ministry of Health - DRO/ ; },
abstract = {Alzheimer's disease (AD) is a highly complex and multifactorial disorder in which oxidative stress acts as a key amplifying mechanism in the disease progression. Lipofuscin-like pigments (LFP), end products of lipid peroxidation, reflect oxidative damage and are capable of crossing the blood-brain barrier into the circulation. Thus, erythrocyte-derived LFP may serve as peripheral indicators of brain-specific processes. In this study, we aimed to assess the specificity of previously identified LFP for AD pathology. We analysed erythrocyte-derived LFP in individuals with biomarker-verified AD pathology (n = 40) and non-AD cognitive disorders (n = 21) across the prodromal and dementia stages, and in cognitively unimpaired individuals (n = 19). AD individuals showed significantly higher LFP levels compared with both healthy controls (p < 0.003) and the non-AD group (p ≤ 0.001). Furthermore, LFP levels correlated with established AD biomarkers in CSF, including amyloid-beta (r > -0.566) and phosphorylated tau 181 (r < 0.477). Our findings suggest that LFP may serve as potential blood-based biochemical markers reflecting oxidative stress-related processes associated with AD pathology.},
}

@article {pmid41757782,
year = {2026},
author = {Hamidioğlu, S and Şimşek, E},
title = {Emotional Responses and Anticipatory Grief Among Family Caregivers of Alzheimer's Patients: A Cross-Sectional Study.},
journal = {Psychogeriatrics : the official journal of the Japanese Psychogeriatric Society},
volume = {26},
number = {2},
pages = {e70153},
doi = {10.1111/psyg.70153},
pmid = {41757782},
issn = {1479-8301},
abstract = {OBJECTIVE: Alzheimer's disease is the most common type of dementia among older adults, and the caregiving process imposes significant physical, social and emotional burdens on family members. This study aimed to evaluate the emotional responses and anticipatory grief experienced by family caregivers of patients with Alzheimer's disease.

METHODS: This cross-sectional study included 257 primary family caregivers of patients with Alzheimer's disease registered at the Ankara Bilkent City Hospital Home Healthcare Unit. Data were collected using a Sociodemographic Questionnaire and the Marwit-Meuser Caregiver Grief Inventory-Short Form (MM-CGI-SF). Normality was assessed using the Shapiro-Wilk test. Pearson or Spearman correlation analyses were applied as appropriate. Caregiver burden was dichotomised based on the median MM-CGI-SF score and examined using multivariable logistic regression analysis (Backwards LR). p < 0.05 was considered statistically significant.

RESULTS: The median age of caregivers was 56 (range: 25-77) years, and 63.8% were female. Female caregivers, those cohabiting with the patient, and caregivers of patients with moderate-to-severe disease reported significantly higher burden scores. In logistic regression analysis, increasing age and longer time since diagnosis were associated with a lower likelihood of high caregiver burden, whereas female gender, higher disease severity, higher income relative to expenses and cohabitation with the patient were independent predictors of high burden.

CONCLUSION: Family caregivers of patients with Alzheimer's disease experience substantial emotional burden and anticipatory grief. Caregiver burden appears to be shaped more by disease-related and psychosocial factors than by caregiving duration alone. Integrating caregiver assessment and psychosocial support into primary care is essential, with family physicians playing a central role in early identification and intervention.},
}

@article {pmid41757647,
year = {2026},
author = {Huang, C and Ya, J and Zhao, C and Zhang, Y and Liu, M and Du, X and Ren, J and Qu, X},
title = {Chiral Supramolecular Hydrogen Bonding Networks for Enantio-Selective Catalysis Against Neuroinflammation.},
journal = {Angewandte Chemie (International ed. in English)},
volume = {},
number = {},
pages = {e4720702},
doi = {10.1002/anie.4720702},
pmid = {41757647},
issn = {1521-3773},
support = {T249526//National Natural Science Foundation of China/ ; 22437006//National Natural Science Foundation of China/ ; 22237006//National Natural Science Foundation of China/ ; 2022YFA1205804//National Key R&D Program of China/ ; },
abstract = {Non-covalent interactions are critical for regulating protein stability, reshaping catalytic active sites, and facilitating enzymatic reactions. Introducing these interactions into reticular materials offers a new approach to constructing artificial enzymes and more closely mimicking the catalytic microenvironment. Herein, a pair of chiral hydrogen-bonded organic frameworks (LHOF and DHOF) has been constructed, and their unique crystal structures have been determined. These porous chiral HOFs act as substrate enrichment pockets, active cavities, and possess aldolase-like activity, which can catalyze the asymmetric synthesis of the enantiomeric bioactive molecule, 3-hydroxy-1,5-diphenyl-1-pehtanone. Compared to the right-handed enantiomer, the left-handed compound shows superior reactive oxygen species (ROS) scavenging capability in an LPS-induced inflammatory model. Further studies demonstrate that the anti-neuroinflammatory effect of this chiral product can reverse microglia phenotype, thereby enhancing their Aβ phagocytosis and alleviating Alzheimer's disease symptoms in the 3×Tg-AD mouse model. Thus, introduction of non-covalent interactions into reticular materials enhances enzyme-mimicking technology and offers new insights into enantioselective in vivo catalysis. This work provides a new paradigm for developing bioinspired materials chemistry and exploring their applications in enantioselective biomimetic catalysis.},
}

@article {pmid41757607,
year = {2026},
author = {Slama, PS and Macbale, AR and Jedynak, BM},
title = {Association of infections and autoimmune conditions with cognition: a study using self-reported conditions and identifying a novel plasma biomarker.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.02.13.26346282},
pmid = {41757607},
abstract = {BACKGROUND: Over the past couple of decades, the role of infections, as well as the involvement of the immune system, have been highlighted in the development of dementia.

METHOD: Data from the Wisconsin Registry for Alzheimer's Prevention cohort were utilized for the analysis. A history of medical conditions was searched across the cohort, and known infections and autoimmune conditions were recorded for each participant. These conditions were then compared with the diagnosis and cognitive performances of each participant. Furthermore, plasma markers were analyzed using two different protein quantification methods.

RESULTS: Our analysis revealed poorer cognitive performances among participants with listed medical conditions. In plasma samples, Ab42/ICAM1 was identified as a protein ratio with significant variation across condition statuses.

DISCUSSION: Our study confirmed that infections and autoimmune conditions contribute to cognitive decline. Ab42/ICAM1 was identified as a relevant marker.},
}

@article {pmid41757363,
year = {2026},
author = {Eun, Y and Newman, JC and Lee, JH and Kim, SH and Kim, HN},
title = {Endogenous β-hydroxybutyrate and the risk of cognitive decline: a nested case-control study in the UK Biobank cohort.},
journal = {Frontiers in aging neuroscience},
volume = {18},
number = {},
pages = {1768532},
pmid = {41757363},
issn = {1663-4365},
abstract = {INTRODUCTION: β-hydroxybutyrate (BHB) has been linked to improved cognitive function via enhanced cerebral metabolism and anti-inflammatory effects. However, evidence on the relationship between endogenous plasma BHB levels and cognitive decline remains limited. This study investigated whether higher plasma BHB levels are associated with reduced cognitive decline in middle-aged and older adults.

METHODS: We conducted a nested case-control study within the UK Biobank prospective cohort. Among 4,653 participants with baseline plasma BHB measurements and cognitive assessments at baseline and follow-up, 2,143 cases of cognitive decline were matched to 2,143 controls by age, sex, and polygenic risk score for Alzheimer's disease. Plasma BHB concentrations were measured by nuclear magnetic resonance spectroscopy. Cognitive function was assessed across five domains, and a global cognition score was derived through factor analysis. Cognitive decline was defined as a decrease in the global cognition score from baseline to follow-up. Conditional logistic regression and restricted cubic spline models were used to examine the associations between plasma BHB levels and cognitive decline, adjusting for demographic, lifestyle, and clinical factors.

RESULTS: Plasma BHB concentrations were not significantly associated with global cognitive decline after covariate adjustment. However, higher plasma BHB tertiles were associated with a slower decline in fluid intelligence (adjusted OR for tertile 1 vs. 3, 0.83; 95% CI, 0.72-0.97).

DISCUSSION: Endogenous plasma BHB was not significantly associated with global cognitive decline but was inversely related to decline in fluid intelligence. Further studies are needed to clarify BHB's role in cognitive aging.},
}

@article {pmid41757361,
year = {2026},
author = {Lathika Rajendrakumar, A and Arbeev, KG and Bagley, O and Yashin, AI and Ukraintseva, S},
title = {Lower hippocampal volume partly mediates the association between rs6859 in the NECTIN2 gene and Alzheimer's disease: new findings from causal mediation analysis of ADNI data.},
journal = {Frontiers in aging neuroscience},
volume = {18},
number = {},
pages = {1715773},
pmid = {41757361},
issn = {1663-4365},
abstract = {INTRODUCTION: Alzheimer's disease (AD) is a complex disorder influenced by many factors. The rs6859 polymorphism in the NECTIN2 gene has been consistently linked to AD risk. The NECTIN2 is involved in vulnerability to infections, which could contribute to neurodegeneration. We hypothesized that hippocampal volume (HV), a biomarker of neurodegeneration, may mediate the connection between the NECTIN2 polymorphism and AD.

METHODS: The analysis was conducted using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Linear mixed models were used to evaluate the association between SNP rs6859 and normalized hippocampal volumes over time. Multivariable linear and logistic regression models were used to estimate the associations between SNP rs6859 and median hippocampal volumes, and between SNP rs6859 and median hippocampal volumes and AD, adjusting for potential confounders. Causal mediation analyses (CMA) were performed using previously fitted logistic and linear models to estimate the mediating role of hippocampal volumes in the association between rs6859 and AD.

RESULTS: We found that smaller HV significantly mediates the association between rs6859 in NECTIN2 and AD risk. Carrying the rs6859 risk allele (A) was associated with lower right HV (β = -0.16, p = 0.03), left HV (β = -0.14, p = 0.04), and total HV (β = -0.15, p = 0.04) in linear mixed models. These associations were significant only in males. The mediated effects for the right and left HV were 42.75 and 49.76%, respectively.

DISCUSSION: Our results indicate that hippocampal atrophy may mediate the association between NECTIN2 polymorphism and AD risk, although the borderline significance of these associations warrants confirmation in other populations.},
}

@article {pmid41757360,
year = {2026},
author = {Jayaprakash, J and Gizaw, ST and Gowda, D and Hinou, H and Nishimura, SI and Hui, SP and B Gowda, SG},
title = {Brain lipidomics for region-specific biomarker discovery in neurodegenerative diseases.},
journal = {Frontiers in aging neuroscience},
volume = {18},
number = {},
pages = {1757306},
pmid = {41757360},
issn = {1663-4365},
abstract = {BACKGROUND: Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD) are progressive neurodegenerative diseases (NDs) characterized by chronic neuronal loss. The lack of effective treatments highlights the urgent need for reliable lipid biomarkers to enable diagnosis and monitor disease progression. Previous lipidomic investigations of altered lipid metabolism have focused on a single disease type, limiting cross-disease comparisons.

METHODS: We applied the untargeted liquid chromatography-mass spectrometry (LC/MS) technique to profile brain lipidome alterations and to identify disease-specific lipid biomarkers across AD, HD, and PD. Brain tissue samples were collected from four cerebral lobes of healthy volunteers (HV, n = 24) and patients diagnosed with AD (n = 24), PD (n = 24), and HD (n = 24). All groups include three males and three females, with brain tissues from four cortical regions sacrificed from each individual.

RESULTS: A total of 243 lipid molecular species spanning five major classes were annotated, revealing distinct disease-specific lipidomic profiles that differentiated HV from the AD, HD, and PD groups via multivariate analysis. Sphingomyelins and oxidized phosphatidylserine [PS (16:1/24:0;O1)] were significantly increased, while lysophosphatidylcholines (LPC 18:2, LPC 17:2) were decreased in the AD group relative to HV. HD exhibited elevated PS (O-17:0/22:6) and ω-6 fatty acid esterified cholesteryl esters (CE 18:2, CE 20:4), alongside decreased essential neuronal lipids such as phosphatidylinositols (PI). The PD lipidome alterations closely resembled those of HD, indicating partially overlapping disruptions in brain lipid metabolism. Receiver operating characteristic analysis identified PS (16:1/24:0;O1), PS (O-17:0/22:6), and PI (18:1/18:1) as potential discriminatory biomarkers with strong diagnostic performance. Regional heatmap analysis revealed significant lipid perturbations were observed in the parietal and occipital lobes across all NDs.

CONCLUSION: This study provides a comprehensive overview of disease- and region-specific alterations in the brain lipidome of AD, HD, and PD. The identified lipid species-PS (16:1/24:0;O1), PS (O-17:0/22:6), and PI (18:1/18:1)-may serve as promising candidate biomarkers for NDs diagnosis and warrant further mechanistic and longitudinal validation with large data set.},
}