@article {pmid42261688,
year = {2026},
author = {Broncel, A and Konopacki, J and David, TB and Galecki, P and Ben-Menachem, E and Krawczyk, M},
title = {Nocturnal vagus nerve stimulation enhances cognitive functions in patients with early Alzheimer's disease.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261458276},
doi = {10.1177/13872877261458276},
pmid = {42261688},
issn = {1875-8908},
abstract = {BackgroundAuricular transcutaneous vagus nerve stimulation (atVNS) has been proposed as a non-invasive neuromodulation approach for cognitive disorders, including Alzheimer's disease (AD). Sleep represents a physiological state characterized by enhanced vagal activity and memory consolidation, making it a potentially optimal window for stimulation.ObjectiveTo investigate the cognitive effects of nocturnal atVNS in individuals diagnosed with mild cognitive impairment (MCI) and AD.MethodsParticipants underwent nightly atVNS using a Vguard device, specifically designed for non-invasive stimulation during sleep. Cognitive performance was evaluated using four standardized neuropsychological instruments, including the Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS-Cog).ResultsRepeated nocturnal atVNS over several months was associated with significant improvements in global cognitive function. Among the administered tests, the ADAS-Cog demonstrated the greatest sensitivity in detecting stimulation-related changes.ConclusionsNocturnal atVNS may constitute a promising therapeutic strategy for enhancing cognition in patients with MCI and AD. By leveraging sleep-related vagal activity, this approach could potentially delay or prevent the progression of MCI to AD and dementia.},
}

@article {pmid42261694,
year = {2026},
author = {Vassilaki, M and Smith, SM and Loftin, TM and Mohamed, EA and Rethemeier, N and Coburn, RP and Graff-Radford, J and Petersen, RC and Boeve, BF and Lunde, AM},
title = {Reflections on rural community characteristics by an outreach, recruitment, and engagement team.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261454612},
doi = {10.1177/13872877261454612},
pmid = {42261694},
issn = {1875-8908},
abstract = {Rural populations are underrepresented in cognitive impairment research and have limited resources for education about brain and cognitive health, Alzheimer's disease and related dementias, or caregiving. As our Outreach, Recruitment, and Engagement team aimed to expand activities into more rural communities, we also wanted to better understand the characteristics of the communities surrounding our center and gain insight into the social exposome of the areas. The goal of the manuscript is to reflect on our experience and share measures that were useful in this effort, which can be further enriched and adjusted by other outreach teams.},
}

@article {pmid42261695,
year = {2026},
author = {Lopes Cardoso, I and Guimarães, MI and Tubiana, E and Gavinha, S},
title = {The relationship between Porphyromonas gingivalis infection and the development of Alzheimer's disease: A scoping review.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261456716},
doi = {10.1177/13872877261456716},
pmid = {42261695},
issn = {1875-8908},
abstract = {BackgroundAlzheimer's disease is the leading cause of dementia and constitutes a major public health problem. Recent research suggests that certain chronic infections, particularly periodontal infections, may play a role in the development or progression of this disease. Among the bacteria involved in periodontal disease, Porphyromonas gingivalis has attracted particular attention from researchers.ObjectiveIn this way, the aim of this thesis, conducted in the form of a scoping review, was to analyze existing scientific data on the relationship between Porphyromonas gingivalis infection and Alzheimer's disease.MethodsTo achieve this, a literature search was conducted in several scientific databases leading to the selection of fourteen studies that met the inclusion criteria.ResultsSome of the selected studies have shown the presence of Porphyromonas gingivalis or its virulence factors in the brain tissues of patients with Alzheimer's disease. Experimental studies also indicate that this bacterium can promote certain mechanisms involved in neurodegeneration, namely inflammation and accumulation of amyloid-β.ConclusionsSelected studies point to the existence of an association between exposure to periodontal bacteria and an increased risk of developing Alzheimer's disease.},
}

@article {pmid42261703,
year = {2026},
author = {Acquaviva, J and Delic, V and Bellacicco, N and Choi, YB},
title = {Blood-based biomarkers for dementia with Lewy bodies.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261456317},
doi = {10.1177/13872877261456317},
pmid = {42261703},
issn = {1875-8908},
abstract = {Dementia with Lewy bodies (DLB), a synucleinopathy, is the second most common form of dementia after Alzheimer's disease (AD). Yet, DLB is often more aggressive and clinically challenging to diagnose due to overlapping symptoms with AD and Parkinson's disease dementia. Reliable biomarkers are necessary, since a definitive diagnosis of DLB currently requires postmortem tissue analysis. Blood-based biomarkers represent a minimally invasive and cost-effective avenue for earlier and more accurate diagnosis. This review integrates current evidence on blood biomarkers for DLB, at times extrapolated from other synucleinopathies, with a focus on α-synuclein and its derivatives, including extracellular vesicle-associated α-synuclein, seeding amplification assays, and autoantibodies. Additional biomarkers such as phosphorylated tau and amyloid-β highlight the frequent co-pathology with AD, while markers of neurodegeneration, neuroinflammation, and oxidative stress, heart-type fatty acid-binding protein, proteomic profiling, lipid, and other metabolites offer complementary diagnostic and prognostic potential. Although no single blood biomarker currently provides definitive diagnostic, differential, and prognostic accuracy for DLB, the studies reviewed here provide converging evidence that combined blood-based biomarker panels may offer meaningful clinical promise in facilitating earlier detection, guiding prognosis, and improving the design of targeted therapeutic trials for DLB.},
}

@article {pmid42261705,
year = {2026},
author = {Hölscher, C},
title = {Semaglutide showed limited improvements in patients with Alzheimer's disease: Revisiting the evoke and evoke + clinical trials.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261458402},
doi = {10.1177/13872877261458402},
pmid = {42261705},
issn = {1875-8908},
abstract = {BackgroundSemaglutide is a glucagon-like peptide-1 analog that is on the market to treat type 2 diabetes and weight loss (Ozempic, Wegovy). Two phase 3 clinical trials have been conducted, Evoke and Evoke+, testing the drug in patients with Alzheimer's disease. The trial management presented results of the intermediate readout at week 104 of the CDR-SB scores, which were negative. On the basis of that, the management decided to declare the trials a failure. However, data from week 130 and 156 had not been statistically analyzed.ObjectiveWhen evaluating time points 130 and 156, several results show a separation between drug group and placebo group with semaglutide showing better results.MethodsUsing the means, converting the SEMs to SDs and numbers of patients per group, I analyzed the results using the Welch T-test (two-tailed), which does not assume equal SD.ResultsThe ADCS-ADL-MCI test, Evoke trial, week 130, did show a significant difference, p = 0.0039. Other test such as the ADAS-cog-13 results show trends towards improvement by semaglutide at week 156. Cerebrospinal fluid biomarker analyses showed significant differences in some AD markers, too.ConclusionsThe results did show some limited drug effects at later time points of the trials. However, Semaglutide has been designed to stay in the blood for a long time and therefore does not cross the blood-brain barrier readily. Novel GLP-1 type drugs that can cross the blood-brain barrier easily may show superior protective effects in AD patients.},
}

@article {pmid42261707,
year = {2026},
author = {Alghamdi, A and Combrtg, E and Balafas, S and Bos, JHJ and Van Munster, BC and Schmidt, M and Hak, E},
title = {Exploring the repurposing potential of β2-adrenergic receptor agonists for cognitive function: Evidence from the PharmLines Initiative Retrospective Cohort Study.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261457957},
doi = {10.1177/13872877261457957},
pmid = {42261707},
issn = {1875-8908},
abstract = {BackgroundPreclinical studies suggest β2-adrenergic receptor agonists may exert neuroprotective effects, but evidence in human populations is limited.ObjectiveTo examine the association between β2-adrenergic receptor agonist use and cognitive performance in older adults.MethodsThis retrospective cohort study linked Dutch pharmacy dispensing records (IADB.nl) with Lifelines cohort data. Participants aged ≥50 years with ≥1 prescription for β2-adrenergic receptor agonists or reference medications (COPD/cardiovascular) within 365 days prior to baseline cognitive testing were included. Cognitive function was assessed using the Cogstate Brief Battery. Linear mixed models adjusted for demographic, clinical, and lifestyle factors evaluated longitudinal changes.ResultsA total of 3179 participants were included (249 β2-adrenergic receptor agonist users, 2930 reference). The exposed group was younger (mean age 58.6 ± 7.4 years versus 63.7 ± 9 years) and included a higher proportion of females (68.2% versus 58.6%) compared with the referent group. At baseline, groups were similar in most cognitive domains, except for slightly higher attention (COG2) scores in the reference group (p = 0.010). Over time, psychomotor speed (COG1), attention (COG2), and visual learning (COG4) remained stable across groups. Working memory (COG3) declined significantly in both groups, with a steeper decline in the reference cohort (p = 0.048).ConclusionsIn this exploratory cohort study, β2-adrenergic receptor agonist use was not associated with broad cognitive benefits, though a modest attenuation of working memory decline was observed. These results highlight the need for larger, prospective studies to clarify whether specific subgroups or drug formulations may offer cognitive advantages.},
}

@article {pmid42261770,
year = {2026},
author = {Zhang, L and Yang, C and Yao, Q and Du, X and Ding, S and Shi, Y and Sheng, C and Wang, M and Han, Y and Luo, H},
title = {Machine Learning-Enhanced Ultrasensitive Immuno-CRISPR Array Facilitates Early Diagnosis of Alzheimer's Disease by Detecting Multiple Plasma Biomarkers.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {},
number = {},
pages = {e75983},
doi = {10.1002/advs.75983},
pmid = {42261770},
issn = {2198-3844},
support = {82401859//National Natural Science Foundation of China/ ; XKTP2025B04//First-class Discipline Breakthrough Initiative of Hainan University/ ; 826MS0122//Hainan Provincial Natural Science Foundation of China/ ; 826QN0570//Hainan Provincial Natural Science Foundation of China/ ; 825QN284//Hainan Provincial Natural Science Foundation of China/ ; },
abstract = {Early and accurate diagnosis of Alzheimer's disease (AD) remains a significant challenge due to the multifactorial and dynamic nature of its pathology. Although plasma-based biomarkers such as amyloid-β (Aβ) and phosphorylated tau (p-tau) have shown promise as diagnostic indicators, current single-biomarker detection techniques lack the requisite sensitivity and specificity for early-stage diagnosis. Here, we present the development of an ultrasensitive CRISPR-based multi-protein detection array (UCMDA) capable of concurrently detecting six core AD biomarkers, including Aβ40, Aβ42, p-tau[181], p-tau[217], p-tau[231], and p-tau[396,404]. By integrating antibody pair-based multiplex recombinase polymerase amplification (RPA) with spatially encoded CRISPR-Cas12a detection, the UCMDA achieves a detection limit of 1 fg/mL, which is 10 000-fold more sensitive than conventional ELISA. Clinical validation in a cohort of 155 plasma samples demonstrated that logistic regression (LR)-based integration of the six biomarkers significantly enhanced diagnostic performance, with the multi-biomarker model substantially outperforming single-biomarker approaches in diagnosing AD-MCI and AD. This platform offers a scalable, cost-effective, and minimally invasive strategy for early detection and disease monitoring. This work highlights the potential of CRISPR-based multiplex protein detection technologies combined with machine learning-assisted analysis to enhance the precision of diagnosing neurodegenerative disorders.},
}

@article {pmid42261981,
year = {2026},
author = {Hatano, T and Lin, CH and Cardoso, F},
title = {A Biological Framework for Parkinson's Disease: Advances in α-Synuclein-Centered Biomarkers and Staging.},
journal = {Journal of neurochemistry},
volume = {170},
number = {6},
pages = {e70491},
doi = {10.1111/jnc.70491},
pmid = {42261981},
issn = {1471-4159},
support = {25wm0625127//Japan Agency for Medical Research and Development/ ; 25wm0625126//Japan Agency for Medical Research and Development/ ; 25wm0625503//Japan Agency for Medical Research and Development/ ; 24dk0207072//Japan Agency for Medical Research and Development/ ; 24wm0425015//Japan Agency for Medical Research and Development/ ; 24wm0425019//Japan Agency for Medical Research and Development/ ; 24bm1423015//Japan Agency for Medical Research and Development/ ; 24dk0207055//Japan Agency for Medical Research and Development/ ; 24K02373//Japan Society for the Promotion of Science/ ; },
abstract = {Parkinson's disease (PD) is a neurodegenerative disorder marked by substantial heterogeneity in pathological distribution, disease trajectories, and coexisting neuropathologies. Despite this biological complexity, current diagnosis and staging of PD remain largely anchored in clinical manifestations. Neuronal aggregation of misfolded α-synuclein and degeneration of the nigrostriatal dopaminergic system precede the onset of motor symptoms; this phase is termed the prodromal stage of PD. Therefore, clinically based frameworks inherently limit early detection and stratification. In contrast, Alzheimer's disease has undergone a paradigm shift toward a biomarker-driven biological definition, prompting a similar reappraisal of PD as a biologically defined disease continuum. Accumulating evidence indicates that pathological α-synuclein aggregates in PD extend beyond the central nervous system and exhibit heterogeneous patterns of initiation and propagation. Methodological advances have expanded the capacity to detect these pathological species in vivo. In particular, α-synuclein seed amplification assays (SAA) enable the detection of seeding-competent α-synuclein species in biofluids and peripheral tissues, providing evidence consistent with α-synuclein pathology; however, SAA should not be interpreted as a direct reflection of disease stage, progression, or pathological burden. Furthermore, the development of α-synuclein positron emission tomography ligands offers the prospect of non-invasive visualization of pathological burden, spatial distribution, and longitudinal target engagement, thereby complementing biofluid-based approaches. Together, these biomarker advances underpin emerging biologically anchored classification and staging frameworks, such as the SynNeurGe system and the Neuronal α-Synuclein Disease Integrated Staging System (NSD-ISS). These frameworks integrate α-synuclein pathology, neurodegeneration, genetic background, and clinical features to define disease identity and progression across asymptomatic, prodromal, and manifest stages. We synthesize recent advances in α-synuclein-centered biomarkers and biological staging frameworks and discuss how their convergence is beginning to reshape PD from a primarily symptom-based diagnosis toward a molecularly grounded disease continuum. This transition has the potential to complement clinically defined PD with biologically informed perspectives.},
}

@article {pmid42262514,
year = {2026},
author = {Chlebowski, RT and Rapp, S and Aragaki, AK and Manson, JE and Pan, K and Neuhouser, ML and Johnson, KC and Snetselaar, LG and Henderson, VW and Qi, L and Hayden, KM and Baker, LD and Garcia, O and Pichardo, MD and Wactawski-Wende, J and Prentice, RL},
title = {Low-fat dietary pattern and dementia mortality: a secondary analysis of the Women's Health Initiative dietary modification randomized clinical trial with long-term follow-up.},
journal = {Menopause (New York, N.Y.)},
volume = {},
number = {},
pages = {},
pmid = {42262514},
issn = {1530-0374},
abstract = {OBJECTIVES: In the Women's Health Initiative (WHI) Dietary Modification (DM) randomized trial, the dietary intervention significantly reduced breast cancer mortality and, in a subgroup of women 65 years old or above, significantly lowered possible cognitive impairment based on Modified Mini-State Examination (3MSE) scores. Based on this background, we examined the dietary intervention association with long-term dementia mortality.

METHODS: The WHI DM clinical trial randomized 48,835 postmenopausal US women, aged 50-79 years, with dietary fat intake ≥32% of energy and anticipated ≥3-year survival. Cognitive function was not an eligibility criterion. Randomization was to a low-fat dietary pattern intervention (40%; n=19,541) with goals to reduce fat intake and increase fruit, vegetable, and grain intake or a usual diet comparison (60%; n=29,294). All dietary targets were significantly reduced. Mortality findings were confirmed by central medical record review enhanced by serial National Death Index findings. Dementia mortality was examined after an 8.5-year (median) dietary intervention and 20-year cumulative follow-up.

RESULTS: Dietary intervention did not influence dementia mortality (n=1,386) (HR: 0.94, 95% CI: 0.85-1.05), with similar findings for Alzheimer (HR: 1.00, 95% CI 0.85-1.17) and non-Alzheimer dementia mortality (HR: 0.90, 95% CI 0.77-1.05). Of 13 subgroup analyses, with dietary intervention, there was a trend for lower dementia mortality in younger women (50-59 y, HR: 0.73, 95% CI: 0.44-1.21; 60-69 y, HR: 0.85, 95% CI: 0.72-1.01; 70-79 y, HR: 1.06, 95% CI: 0.91-1.23; P-trend 0.03).

CONCLUSIONS: A low-fat eating pattern did not reduce dementia mortality in postmenopausal women.},
}

@article {pmid42262533,
year = {2026},
author = {Korade, G and Kharat, S and Rathi, K},
title = {Nitric oxide in neuroinflammation and neurodegeneration: dual roles, inflammasome crosstalk, and biomarker opportunities.},
journal = {Naunyn-Schmiedeberg's archives of pharmacology},
volume = {},
number = {},
pages = {},
pmid = {42262533},
issn = {1432-1912},
abstract = {Nitric oxide is a short-lived gas that plays a critical role in numerous physiological processes, including vascular regulation, neurotransmission, and immune responses. In the CNS NO's role is complex, as it can both protect and damage neurons. Microglia, the brain's resident macrophages, produce excessive NO in response to stimuli like endotoxins and cytokines, leading to chronic inflammation and neuronal damage associated with neurodegenerative diseases such as Alzheimer's, Parkinson's, multiple sclerosis, and amyotrophic lateral sclerosis. NO's dual role as a pro-inflammatory and anti-inflammatory mediator is intricately linked to its impact on neuronal health and disease progression. This review is aimed at summarizing and critically discussing the roles of NO in neuroinflammation, neurodegeneration, inflammasome regulation, and related therapeutic perspectives. A narrative literature review was conducted using electronic databases (e.g. PubMed and Google Scholar) to identify experimental and clinical studies on NO, neuroinflammation, neurodegenerative diseases, inflammasomes, and related biomarkers and therapies, with emphasis on mechanistic and translational work. Research into NO's effects on inflammasomes, key components of the innate immune system, reveals that NO can inhibit inflammasome activation, influencing inflammatory responses. Despite progress, challenges remain, including the need for cell-type-specific models, advanced technological approaches, and the development of selective NO modulators. Overall, current evidence indicates that NO exerts both neuroprotective and neurotoxic effects in the CNS, mediated by its complex interactions with neural, glial, and immune pathways. Future research should focus on the dual nature of NO, explore lesser-known inflammasomes, and incorporate human-centric models to develop targeted therapies.},
}

@article {pmid42262554,
year = {2026},
author = {Paulzen, M},
title = {[Dextromethorphan-bupropion for the treatment of agitation in Alzheimer's disease].},
journal = {Der Nervenarzt},
volume = {},
number = {},
pages = {},
pmid = {42262554},
issn = {1433-0407},
}

@article {pmid42262616,
year = {2026},
author = {Zhang, M and Shi, L and Dong, Y and Sun, Y and Zhu, S and Jin, Q},
title = {Splenic treg-related immunoregulation in the spleen-brain axis of alzheimer's disease: mechanisms and translational strategies.},
journal = {Molecular biology reports},
volume = {53},
number = {1},
pages = {},
pmid = {42262616},
issn = {1573-4978},
support = {KYCX25_3955//The Postgraduate Research & Practice Innovation Program of Jiangsu Province/ ; KYCX25_3954//The Postgraduate Research & Practice Innovation Program of Jiangsu Province/ ; },
abstract = {Alzheimer's disease (AD) is traditionally characterized by amyloid-β (Aβ) plaque deposition, tau pathology, and neuroinflammation in the brain. Increasing evidence highlights the contribution of systemic immune dysregulation to AD progression, in which the spleen may serve as an important peripheral immune organ for sensing and integrating circulating signals. Splenic regulatory T cells (Tregs) contribute to immune tolerance and may shape myeloid-cell inflammatory and phagocytic functions, positioning them as potential modulators of how peripheral immune responses influence brain pathology. During AD progression, alterations in splenic Tregs may be associated with impaired systemic clearance and delayed resolution of inflammation, thereby potentially amplifying the crosstalk between peripheral and central pathological processes. This review synthesizes current knowledge on the spleen-brain axis, discusses potential mechanisms by which splenic Tregs regulate peripheral immune homeostasis, and highlights therapeutic strategies that leverage Treg-mediated immunoregulation to modulate AD-related pathological processes. These insights provide a foundation for exploring whether interventions that modulate splenic Treg function may influence disease progression in AD.},
}

@article {pmid42262975,
year = {2026},
author = {Kaur, SD and Singh, V and Kaurav, H and Nangare, S and Vihal, S},
title = {A review on thymoquinone: a promising therapeutic molecule in Alzheimer's.},
journal = {Nutritional neuroscience},
volume = {},
number = {},
pages = {1-16},
doi = {10.1080/1028415X.2026.2682949},
pmid = {42262975},
issn = {1476-8305},
abstract = {Alzheimer's disease (AD) is a neurodegenerative disorder characterized by memory loss, cognitive decline, amyloid-β deposition, tau pathology, oxidative stress, and neuroinflammation. Thymoquinone (TQ), the principal bioactive constituent of Nigella sativa (NS), has emerged as a promising candidate for AD management because of its neuroprotective properties. This review summarizes current evidence on the therapeutic potential of TQ in AD, with emphasis on its antioxidant, anti-inflammatory, anti-amyloid, anti-tau, and cholinergic-modulating actions. Experimental studies indicate that TQ can reduce oxidative damage, suppress NF-κB- and TLR-associated inflammatory signaling, limit amyloid-β accumulation, modulate tau-related pathology, and improve neuronal survival and cognitive performance in several AD models. The review also discusses delivery strategies to improve the bioavailability and brain targeting of TQ, including nanoformulation-based approaches. Although the available pre-clinical findings support the therapeutic promise of TQ. The well-designed clinical studies are required to establish its efficacy, safety, optimal dosing, and long-term translational value in treating AD.},
}

@article {pmid42263047,
year = {2026},
author = {Jiang, H and Chen, Z and Liu, Y and Yang, C and Yuan, X and He, R},
title = {Correction: The structure of spontaneous speech changes in Alzheimer's disease: Crosslingual evidence from English and Greek.},
journal = {PloS one},
volume = {21},
number = {6},
pages = {e0351467},
doi = {10.1371/journal.pone.0351467},
pmid = {42263047},
issn = {1932-6203},
abstract = {[This corrects the article DOI: 10.1371/journal.pone.0324270.].},
}

@article {pmid42263197,
year = {2026},
author = {Miller, D and Lambert, S and Jordan, L and Butler, MJ and Sinvani, L and Perrin, A and Cheung, YK and Davidson, KW and Goodwin, AM},
title = {Multicomponent Behavior Change Technique Intervention for Caregivers of People With Alzheimer Disease and Related Dementias: Protocol for a Single-Arm, Personalized Behavioral Trial to Disrupt Sedentary Time.},
journal = {JMIR research protocols},
volume = {15},
number = {},
pages = {e82857},
doi = {10.2196/82857},
pmid = {42263197},
issn = {1929-0748},
abstract = {BACKGROUND: Sedentary behavior is associated with negative health outcomes. High levels of sedentary behavior are common among Alzheimer disease and related dementias (ADRD) caregivers already at risk of other adverse health effects, yet few interventions target sedentary behavior within this population. There is a need for trials intended to reduce time spent sedentary, which may be achievable by increasing the frequency of disruptions to sedentary time. Remotely delivered behavior change techniques (BCTs) may be effective for disrupting sedentary behavior in this population through short bursts of walking, although it is unclear how BCTs promote this behavior and potentially act via the hypothesized mechanism of behavioral automaticity.

OBJECTIVE: The goal of the trial is to examine whether a significant proportion of ADRD caregivers (≥50%) receiving an SMS text message-delivered BCT intervention form a habit to engage in hourly walking 4 times per day, with the broader objective of disrupting sedentary time in this population.

METHODS: This trial is a 12-week, decentralized, single-arm, National Institutes of Health Stage II behavioral trial. The trial will deliver a personalized, multicomponent BCT intervention to disrupt time spent sedentary by encouraging forming a habit of hourly walking among caregivers of persons with ADRD via the key mechanism of behavior change behavioral automaticity. The intervention includes 4 daily SMS text message-delivered BCT components previously used in interventions to disrupt sedentary behavior-Goal setting, Action planning, Prompts/cues, and Self-monitoring. Formation of an hourly walking habit is the primary outcome and will be defined as walking an additional 250 steps or more per hour for the same 4 consecutive hours as set up in a personalized walking plan on 7 consecutive days. Secondary outcomes include evaluating associations between habit formation and behavioral automaticity, and between longitudinal behavioral automaticity and habitual hourly walking over time. Additionally, heterogeneity of treatment effects will be evaluated. Exploratory analyses will examine potential moderating variables that may influence the intervention effect. The trial uses digital enrollment strategies, SMS text message intervention delivery, passive data collection via Fitbit (Google) devices, and online survey assessments to collect data remotely.

RESULTS: This study was funded by the National Institute on Aging in June 2024. Recruitment and data collection began in March 2025. As of August 2025, 40% (n=40) of the planned sample has been enrolled. Data collection is expected to be complete by June 2026. Data analysis and publication of results are expected by Fall and Winter 2026, respectively.

CONCLUSIONS: Results will have the potential to advance knowledge about the effectiveness of BCTs to form a habit of hourly walking and may provide opportunities for future public health impact to promote physical activity in caregivers of those living with ADRD.},
}

@article {pmid42263243,
year = {2026},
author = {Li, X and Xu, J and Du, G and Jia, X and Zhao, D and Zhou, C and Xiao, K and Gu, J and Zhu, J and Shang, X},
title = {Accurately Deciphering Tissue Heterogeneity From Spatial Multi-Modal and Multi-Omics With STransformer.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {},
number = {},
pages = {e75969},
doi = {10.1002/advs.75969},
pmid = {42263243},
issn = {2198-3844},
support = {AM2024027//Macau Young Scholars Program/ ; 62433016//National Natural Science Foundation of China/ ; 2024A1515012602//Guangdong Basic and Applied Basic Research Foundation/ ; 0959202513204//Young Talent Fund of Xi'an Association for Science and Technology/ ; },
abstract = {Advances in spatially resolved technologies enable the simultaneous acquisition of diverse data modalities within a tissue slice while preserving critical spatial context, which presents unprecedented opportunities to decipher intricate tissue heterogeneity. However, existing computational approaches lack the intrinsic flexibility to universally process both spatial multi-modal and multi-omics data. Here, we introduce STransformer, a unified deep learning framework designed to seamlessly accommodate a comprehensive landscape of spatial data. By simultaneously capturing short-range cellular interactions and tissue-wide semantic patterns, it extracts robust representations to accurately dissect complex tissue heterogeneity. Systematic evaluations across diverse species, tissue types, and data modalities highlight its profound versatility. For spatial multi-modal data, STransformer delineates intricate anatomical structures in the human cortex, uncovers pathological mechanisms in Alzheimer's disease, and characterizes dynamic spatiotemporal developmental trajectories during chicken cardiogenesis. Scaling to spatial multi-omics data, STransformer synergizes spatial transcriptomic and proteomic profiles to decipher intricate immune microenvironments within the human tonsil, and jointly analyzes spatial epigenomic and transcriptomic data to infer regulatory mechanisms in the mouse embryonic brain. Consequently, STransformer serves as a highly versatile and robust analytical framework for advancing our understanding of tissue heterogeneity and disease pathogenesis.},
}

@article {pmid42263397,
year = {2026},
author = {Chen, J and Li, G and Yu, K and Cheng, G and Fan, X and Wang, K},
title = {Multimetric brain functional-structural connectivity mutual coupling for mild cognitive impairment identification.},
journal = {Neural networks : the official journal of the International Neural Network Society},
volume = {204},
number = {},
pages = {109232},
doi = {10.1016/j.neunet.2026.109232},
pmid = {42263397},
issn = {1879-2782},
abstract = {Mild cognitive impairment (MCI) is widely recognized as a prodromal stage of many neurodegenerative conditions such as Alzheimer's disease, and its early identification is essential for timely clinical intervention. Multimodal MRI-derived functional connectivity (FC) and structural connectivity (SC) provide complementary views of brain network organization, and learning their coupling patterns has shown promising potential for MCI identification. However, most existing studies construct FC/SC networks using a single quantitative metric and model FC-SC relationships in a unidirectional manner, which may overlook heterogeneous topological characteristics and the intrinsic bidirectional interplay between brain function and structure. To cope with these, we propose a Multimetric Mutual Coupling Network (MMCN) for MCI identification. Specifically, multiple FC and SC metrics are employed to construct subject-specific multimetric connectivity graphs, enabling richer and more robust representations by mitigating single-metric bias. We further design an FC/SC-specific patch embedding module and introduce a cross-guided attention-based patch enhancement mechanism, which explicitly performs bidirectional feature refinement between FC and SC. This mutual coupling strategy facilitates knowledge-informed modeling of the interdependence between neuronal activity and white matter integrity, thereby capturing subtle yet critical connectivity disruptions associated with MCI. Extensive experiments on multimodal MRI data from one public dataset and one local cohort demonstrate the superior performance of MMCN comparing with state-of-the-art methods and highlight the necessity of multimetric-based FC-SC mutual coupling for accurate MCI identification. The codes of MMCN are publicly available at https://github.com/kevin-dgut/MMCN.},
}

@article {pmid42263407,
year = {2026},
author = {Wasilah, H and Gidafie, A and Amelia, VL and Chung, MH},
title = {Effectiveness of morning blue light therapy on sleep and daytime symptoms in adults with primary and comorbid insomnia: A systematic review and meta-analysis of randomized control trials.},
journal = {International journal of nursing studies},
volume = {182},
number = {},
pages = {105588},
doi = {10.1016/j.ijnurstu.2026.105588},
pmid = {42263407},
issn = {1873-491X},
abstract = {BACKGROUND: Insomnia is the most prevalent sleep complaint, occurring as a primary or comorbid condition, increasing the public healthcare burden. Prior reviews examined the efficacy of blue light therapy in improving sleep among patients with a traumatic brain injury and young adults and reported conflicting results. A comprehensive evaluation of blue light therapy on sleep quality, sleep parameters, daytime sleepiness, and fatigue across adults with primary insomnia and insomnia with comorbid condition has not been fully established.

METHODS: This study was conducted in accordance with the PRISMA 2020 statement. We searched EBSCO, Embase, OVID, PubMed, Scopus, Trials.Gov, Web of Science, and PROSPERO for eligible studies published between the date of database inception and 16 April 2025. The Cochrane risk of bias tool was used to assess study quality. A random-effects model was employed to calculate the pooled effects. Subgroup analyses were performed to identify potential moderators.

RESULTS: We included 14 articles involving 444 insomniacs with a neurological disease (mild traumatic brain injury, Alzheimer's disease, or dementia) or medical disease (cancer, diabetes, or fibromyalgia) or with no comorbidity. Studies were conducted in several Asian and European countries, as well as the United States and Australia. The results indicated that blue light therapy improved subjective sleep quality [mean difference (MD) = -1.895], excessive daytime sleepiness (MD = -0.970), and several objective sleep parameters [sleep onset latency (Hedges' g = -0.545), waking after sleep onset (Hedges' g = -0.563), sleep efficiency (Hedges' g = 0.429), sleep fragmentation (Hedges' g = -1.228), and number of awakenings (Hedges' g = -0.614)]. Blue light therapy did not improve the fragmentation index, time in bed, or total sleep time and did not significantly reduce fatigue. The type of device, intervention duration, and light intensity moderated sleep quality. The intervention duration and frequency moderated sleep efficiency.

CONCLUSIONS: In adults with insomnia with diverse clinical backgrounds, blue light therapy may provide modest improvement in sleep quality and certain sleep parameters related to advancement and continuity of sleep (sleep fragmentation, sleep onset latency, waking after sleep onset, number of awakenings, and sleep efficiency), and may alleviate excessive daytime sleepiness. These findings suggest that blue light therapy may be considered potential non-pharmacological treatment for insomnia that can be implemented by healthcare providers in home or clinical settings. However, these findings should be interpreted with caution. Further studies are needed to confirm these findings.

REGISTRATION: The review was registered with PROSPERO (CRD420251027417).},
}

@article {pmid42263657,
year = {2026},
author = {Kim, E and Yu, X},
title = {Astrocyte-microglia crosstalk unlocks Alzheimer's disease.},
journal = {Immunity},
volume = {59},
number = {6},
pages = {1478-1480},
doi = {10.1016/j.immuni.2026.05.004},
pmid = {42263657},
issn = {1097-4180},
abstract = {Altered astrocyte-microglia interactions have been implicated in the pathogenesis of Alzheimer's disease, but the underpinning mechanisms remain unclear. Zhang and colleagues show that astrocytic PAD2-mediated citrullination of vimentin activates microglia, worsens Aβ accumulation, and exacerbates cognitive deficits. These findings highlight astrocyte-microglia crosstalk as a potential therapeutic target for Alzheimer's disease.},
}

@article {pmid42263671,
year = {2026},
author = {Hu, P and Guo, S and Ren, Y and Zhao, R and Su, L and Cheng, J and Tian, X},
title = {A Polarity-Sensitive Lipid Droplet Probe Reveals Aβ Species-Dependent Lipid Droplet Remodeling in Microglia.},
journal = {ACS sensors},
volume = {},
number = {},
pages = {},
doi = {10.1021/acssensors.6c01055},
pmid = {42263671},
issn = {2379-3694},
abstract = {Microglial lipid metabolic alterations are increasingly implicated in Alzheimer's disease (AD), yet the specific β-amyloid (Aβ) species involved in lipid droplet (LD) remodeling remain unclear. Precise visualization of LD morphology in complex biological systems is limited by the availability of selective and photostable probes. Herein, we report a polarity-sensitive LD probe, BODIPY-LD, constructed with a donor-π-acceptor-π-donor (D-π-A-π-D) framework that enables hydrophobic targeting and intramolecular charge transfer (ICT)-based fluorescence activation in low-polarity environments. The probe allows high-contrast visualization and quantitative assessment of LD morphology in cells and brain tissues. Using BODIPY-LD, we observed increased LD burden in hippocampal microglia of APP/PS1 mice and systematically compared the effects of different Aβ25-35 assembly states on LD accumulation in BV2 microglia. Among monomeric, oligomeric, and fibrillar Aβ25-35 forms, the monomer-treated BV2 cells showed the most pronounced LD enrichment under our experimental conditions. This LD-rich phenotype was associated with reduced phagocytic capacity and was partially reversible upon inhibition of LD synthesis using the long-chain acyl-CoA synthetases (ACSL) inhibitor Triacsin C. Together, these findings suggest that monomeric Aβ25-35 is associated with an LD-rich microglial phenotype and impaired phagocytic function in vitro model. Beyond this biological observation, BODIPY-LD provides a useful tool for studying lipid remodeling in neuroinflammatory contexts.},
}

@article {pmid42263678,
year = {2026},
author = {Liu, Y and Ye, Y and Fan, M and Cheng, HY and Sun, S and Qiu, Z},
title = {Epigenetic control of microglial mitochondrial immunity by KAT7 drives Alzheimer's disease pathogenesis.},
journal = {Neuron},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.neuron.2026.05.015},
pmid = {42263678},
issn = {1097-4199},
abstract = {Mitochondrial DNA (mtDNA)-driven innate immune signaling sustains chronic neuroinflammation in neurological diseases such as Alzheimer's disease (AD), yet how this pathway is regulated in microglia remains poorly understood. Here, we identify the histone acetyltransferase KAT7 (HBO1) as a central epigenetic regulator that links chromatin remodeling to mitochondrial immune activation. KAT7 and its histone mark H3K14ac are elevated in microglia from 5×FAD mice and human AD brains. Integrative transcriptomic and epigenomic analyses reveal that KAT7 activates transcription of cytidine/uridine monophosphate kinase 2 (Cmpk2), a mitochondrial kinase essential for mtDNA synthesis. Loss of KAT7 reduces Cmpk2 expression, impairs mtDNA replication and release, and consequently suppresses cyclic guanosine monophosphate-AMP synthase (cGAS)-stimulator of interferon genes (STING) and NLRP3 signaling. Importantly, both microglia-specific deletion and pharmacological inhibition of KAT7 mitigate cytosolic mtDNA-induced neuroinflammation, decrease β-amyloid burden, restore synaptic plasticity, and improve cognitive function in 5×FAD mice. Together, these findings uncover an epigenetic-mitochondrial axis sustaining microglial pathogenicity and establish KAT7 as a potential therapeutic target for AD.},
}

@article {pmid42263789,
year = {2026},
author = {Ding, R and Zhang, T and Liu, G and Huang, Y and Zhao, M and Luo, Y},
title = {Infection and increased risk of incident dementia: the role of biological aging.},
journal = {Brain, behavior, and immunity},
volume = {},
number = {},
pages = {106862},
doi = {10.1016/j.bbi.2026.106862},
pmid = {42263789},
issn = {1090-2139},
abstract = {BACKGROUNDS: It is unclear how the contribution of infectious diseases to dementia risk compares to that of accelerated biological aging. Our study aims to evaluate the associations between infectious diseases and dementia, and assess whether accelerated biological aging moderates the relationship between infection and dementia risk.

METHODS: This study conducted a prospective study involving 339 463 participants aged 37-73 years from the UK Biobank cohort data across 2006 and 2010. Hospital-treated infectious diseases and dementia were identified through record linkage to Health Episode Statistics and Scottish Morbidity Records. Cox regression models were used to assess the association between hospital-treated infections and the risk of developing dementia. Phenotypic age was derived from a validated mortality risk algorithm developed using the National Health and Nutrition Examination Survey (NHANES) III data (Tanaka et al., 2018). Cox proportional hazards models were used to evaluate associations between infections and dementia (all-cause dementia: dementia, young-onset dementia: YOD, vascular dementia: VD and Alzheimer's Disease: AD).

RESULTS: Over a follow-up of 13.51 years, 5, 638incident dementia cases were identified. Hospital-treated infectious diseases were significantly associated with an increased risk of dementia (HR = 2.39, 95 % CI: 2.25-2.53). Consistent patterns emerged across pathogen types, clinical severity categories, and anatomical sites, with most infections showing significant associations with increased young-onset dementia risk. And this effect was consistent among both APOE ε4 carriers and non-carriers, as well as across dementia subtypes and across different sociodemographic groups. The interaction between phenotypic age and infection was significant with the risk of dementia (HR = 1.20, 95 % CI: 1.06-1.37), indicating that the association between infection-related hospitalization and dementia incidence was stronger among biologically older individuals, as determined by their phenotypic age acceleration status.

CONCLUSIONS: Infection associated with the increased risk of dementia, including the risk of AD, VD, and YOD, and the accelerated phenotypic aging further intensifies the association between infection and dementia. APOE ε4 carrier status modifies both the age-stratified relationship between infection and dementia and the moderating effect of accelerated phenotypic aging. Our findings highlight the importance of infection prevention and anti-aging interventions as potential strategies for dementia prevention, and underscore the need to consider APOE ε4 carrier status and age stratification when designing such strategies.},
}

@article {pmid42263829,
year = {2026},
author = {Liu, Y and Fu, R and Ge, C and Long, Z and Wang, H and He, G},
title = {Multi-omics analysis identifies the miR-28a-5p/SerpinA3N/PI3K/AKT axis as a regulator of microglial neuroinflammation and cognitive decline in Alzheimer's disease.},
journal = {Brain research bulletin},
volume = {},
number = {},
pages = {111994},
doi = {10.1016/j.brainresbull.2026.111994},
pmid = {42263829},
issn = {1873-2747},
abstract = {INTRODUCTION: Neuroinflammation driven by microglial dysfunction is a central pathological feature of Alzheimer's disease (AD). However, the precise regulatory networks, particularly those involving post-transcriptional control by microRNAs (miRNAs), remain incompletely understood.

METHODS: We performed integrated multi-omics analysis (miRNA-seq, mRNA-seq, TMT-based proteomics) on hippocampal tissues from APP/PS1 and wild-type mice. Functional validation was conducted in vitro using BV2 microglial cells and in vivo via stereotaxic injection of miR-28a-5p agomir in APP/PS1 mice, combined with molecular, inflammatory, and behavioral assessments.

RESULTS: Multi-omics integration identified SerpinA3N as a core upregulated target in a high-confidence miRNA-mRNA-protein network, with good discriminative ability across AD mouse models. SerpinA3N promoted microglial M1 polarization, enhanced TNF-α/IL-1β/IL-6 secretion, and suppressed the M2 marker Arg1 by inhibiting the PI3K/AKT pathway. miR-28a-5p was identified as a direct upstream repressor of SerpinA3N, and its downregulation in AD models contributed to SerpinA3N upregulation. Rescue experiments confirmed SerpinA3N mediates miR-28a-5p's neuroinflammatory effects. In vivo, miR-28a-5p overexpression reduced SerpinA3N, restored PI3K/AKT activity, alleviated neuroinflammation, and improved learning/memory deficits in APP/PS1 mice.

CONCLUSION: Our study defines a novel miR-28a-5p/SerpinA3N/PI3K/AKT regulatory axis governing pro-inflammatory microglial activation and cognitive function in AD. SerpinA3N and miR-28a-5p show potential as preclinical research biomarkers in AD.},
}

@article {pmid42263916,
year = {2026},
author = {Sandrine, MNY and Blondelle, NM and Franklin, ZG and Emmanuel, OP and Ronald, BAG and Cynthia, BYP and Ogunlakin, AD and Claude, BD and Samir, C and Désiré, DDP},
title = {Neuroprotective Effects of Aqueous Extract of Pterocarpus mildbraedii Harms. on Some Biochemical Markers in Alzheimer's Disease Using an AlCl3-induced Rat Model: Integrated ADMET, Network Pharmacology, Molecular Docking, and In Vivo Experimental Validation.},
journal = {Journal of ethnopharmacology},
volume = {},
number = {},
pages = {121962},
doi = {10.1016/j.jep.2026.121962},
pmid = {42263916},
issn = {1872-7573},
abstract = {ETHNOPHARMACOLOGY RELEVANCE: Neurodegenerative diseases such as Alzheimer's often lack effective conventional treatments. Phytotherapy is emerging as a promising approach to managing these conditions. Pterocarpus mildbraedii Harms. (P. mildbraedii), a plant from the Fabaceae family, which is traditionally used to treat convulsions, headaches, and fever. This study is designed to evaluate the neuroprotective effects of the aqueous extract of Pterocarpus mildbraedii Harms. on biochemical markers of Alzheimer's disease in an AlCl3-induced rat model using integrated ADMET, network pharmacology, molecular docking, and in vivo validation.

METHODS: We employed network pharmacology and in silico molecular docking to identify bioactive compounds and assess their binding affinities to key proteins: VCP, MAPK1, MMP9, PTGS1, IL6, and AR. The in vivo experiment lasted 56 days, with 30 animals divided into 5 groups (n = 6 per group). They received daily oral doses of distilled water (10 mL/kg), AlCl3 (75 mg/kg), Donepezil (5 mg/kg) after AlCl3, or P. mildbraedii bark water extract at 150 mg/kg (PM 150) and 300 mg/kg (PM 300) following AlCl3. On Days 23 and 51, all animals underwent open-field and Morris water maze tests. On Day 57, animals were sacrificed, and calcium levels, oxidative markers, and neurotransmitter levels were measured in homogenates from the amygdala, hippocampus, and prefrontal cortex. Histopathological analysis of the hippocampus and amygdala was also conducted.

RESULTS: In silico studies showed that the plant compounds pterocarpan and liquiritigenin bound strongly to VCP, MAPK1, and MMP9, with binding energies lower than those of reference inhibitors, indicating greater stability. In vivo, AlCl3 caused anxiety, locomotor issues (p< 0. 001), memory impairment (p< 0. 001), and disrupted GABA, ACh metabolism, and AChE activity. It also reduced antioxidant levels (p< 0.001), increased pro-oxidants (p< 0.001), and elevated calcium and Tau protein levels compared to the normal control. Treatment with Pterocarpus mildbraedii extract mitigated these effects, reducing anxiety and enhancing memory, locomotion, ACh, and GABA levels, as well as AChE activity. The extract notably decreased Tau protein and MDA concentrations by 80. 57% in the amygdala, 63. 80.57% in the prefrontal cortex, and 63.73. 50% in the hippocampus, and nitrites. It also significantly increased protein levels, GSH (by 6.95-fold in the amygdala, 80.48% in the prefrontal cortex, and 85.75% in the hippocampus), SOD, and catalase activities across brain regions compared with the AlCl3-treated group.

CONCLUSION: These findings suggest that Pterocarpus mildbraedii extract, with its antioxidant, anti-amnesic, and anxiolytic properties, offers neuroprotection and may have neuroprotective effects in Alzheimer 's-like neurotoxicity.},
}

@article {pmid42264112,
year = {2026},
author = {Yoon, D and Myong, Y and Kim, YG and Sim, Y and Cho, JH and Song, Y and Cho, M and Oh, BM and Kim, S},
title = {SMaRT-Net: A Novel Framework of 7T Brain MRI Superresolution for Alzheimer's Disease Diagnosis and Mild Cognitive Impairment Prognostication.},
journal = {NeuroImage},
volume = {},
number = {},
pages = {122042},
doi = {10.1016/j.neuroimage.2026.122042},
pmid = {42264112},
issn = {1095-9572},
abstract = {Ultra-high-field 7T MRI provides superior detail for diagnosing Alzheimer's disease (AD) and mild cognitive impairment (MCI), but limited accessibility restricts clinical use. To bridge this gap, we developed the self-supervised masked attention-based refinement transformer network (SMaRT-Net), a feedback-driven superresolution framework that synthesizes 7T-equivalent MRI (7T*) from standard 3T MRI. The model combines a Barlow Twins-guided latent diffusion model for initial superresolution with a masked attention transformer that refines images through classification feedback, enabling generation of high-resolution brain imaging optimized for diagnostic use. Training was performed in two stages: a paired 3T-7T dataset from healthy adults was used for initial superresolution learning, and the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset, including AD, MCI, and cognitively normal (CN) subjects, was used for refinement and classification. Prognostic evaluation was conducted in distinguishing stable from converting MCI (sMCI vs. cMCI). Image quality was assessed with BRISQUE and NIQE, while diagnostic performance was evaluated using accuracy and AUROC. The generated 7T* MRIs demonstrated superior quality compared to original 3T scans (BRISQUE: 41.6 vs. 43.6; NIQE: 6.2 vs. 6.4). Diagnostic performance improved consistently: AD vs. CN accuracy increased from 0.900 to 0.946, MCI vs. CN from 0.881 to 0.926, and AD vs. MCI from 0.900 to 0.938. Prognostic accuracy for predicting MCI conversion also rose from 0.680 to 0.800. These results highlight the synergistic benefit of combining superresolution with classification-guided refinement, demonstrating the potential of SMaRT-Net as a scalable tool for improving early diagnosis and prognosis of neurodegenerative disease using routine 3T MRI.},
}

@article {pmid42264167,
year = {2026},
author = {Cavelier, G},
title = {Brain entangled quantum states in radical pairs: a possible link to consciousness.},
journal = {Brain research},
volume = {},
number = {},
pages = {150405},
doi = {10.1016/j.brainres.2026.150405},
pmid = {42264167},
issn = {1872-6240},
abstract = {Current approaches to the study of consciousness have significantly advanced our understanding of this widespread phenomenon in neurocognitive science. Research involving EEG oscillatory dynamics and electromagnetic field activity within brain tissue has provided increasingly detailed insights into arousal states. The neuro-molecular bases of conscious experience have been further clarified, including investigations exploring potential quantum mechanical contributions. However, the precise location, origin, and mechanisms of consciousness within the brain, as well as its connection to fundamental biophysical principles, remain elusive. In this work, we investigate the possible involvement of quantum effects in consciousness by extending rigorous scientific equations and quantum information formalisms-specifically those describing electronic quantum wavefunctions and their parameters-to connect abstract quantum information and photons, atomic, molecular, and neuronal circuit activity, with brain spiking patterns and frequency coding. Testable hypothesis 1: A conscious experience-such as a strong human emotional experience globally connected to sensory perception and the corresponding physical and temporal environment-is registered by the brain through its embedding in N-Methyl-D-Aspartate (NMDA) receptor (NMDAR)-based radical pairs. Local intracranial EEG (iEEG) - Electron Paramagnetic Resonance (EPR) measurements help in supporting the occurrence of such embedding. Hypothesis 1 assessment - Empirical observations that would falsify it: Measurable or inferred parameter values that support the embedding of conscious experience are listed in Tables 1 and 2 and should comply with the ranges and conditions specified therein. Testable hypotheses 2: The NMDAR micropopulation of entangled spin states within relevant radical pairs encodes and transfers sensory and cognitive information of conscious experiences into measurable, stable nanoscale parameters of the quantum iEEG wavefunction. These parameters are transmitted in biconditional manner to the corresponding neuronal spike frequency and timing codes of associated neural circuits. Hypothesis 2 assessment - Empirical observations that would falsify it: iEEG, EEG, EPR, and related radical-pair parameter measurements should comply biconditionally with the relevant neuronal, molecular, and nanoscale measurements and conditions in Tables 1 and 2.},
}

@article {pmid42264186,
year = {2026},
author = {Khan, A and Alzahrani, AR and Rehman, ZU and Singla, N and Shakeel, F and Ali, YH and Saeed, IK and Imran, M},
title = {Impaired Glymphatic Clearance as a Mechanistic Link Between Brain Aging and Neurodegenerative Disease Pathogenesis.},
journal = {Ageing research reviews},
volume = {},
number = {},
pages = {103202},
doi = {10.1016/j.arr.2026.103202},
pmid = {42264186},
issn = {1872-9649},
abstract = {The perivascular glymphatic system promotes cerebrospinal fluid-interstitial fluid (CSF-ISF) interaction and macromolecular waste clearance and is an important determinant of brain homeostasis, the performance of which deteriorates with age. Astrocyte biology, vascular integrity, and age-associated cerebrovascular dynamic alterations interfere with the polarization of aquaporin-4 (AQP4) water channels on astrocytic endfeet, decreasing the clearance of aggregation-prone proteins, such as amyloid-β, tau, and α-synuclein. Experimental research indicates that aging is associated with a decrease in cerebrospinal fluid influx and solute clearance efficiency, and human neuroimaging research indicates progressive age-related dysfunction of glymphatic transport, which is associated with pathological protein accumulation and cognitive impairment. Glymphatic dysfunction is mechanistically associated with clearance failure and disease progression in Alzheimer 's and Parkinson's diseases and is also observed in other age-related diseases, such as cerebral small vessel disease, traumatic brain injury, and neuroinflammatory disease. Emerging evidence suggests that glymphatic efficiency can be restored by intervening in some of the underlying aging processes, including sleep regulation, cardiovascular health, astrocyte-vascular coupling, and pharmacological manipulation of AQP4 polarisation. This review places glymphatic dysfunction as a fundamental, potentially alterable outcome of brain aging with the implication of preventing neurodegenerative diseases and supporting healthy cognitive aging.},
}

@article {pmid42264393,
year = {2026},
author = {Sanchez-Garcia, S and Platt, B and Riedel, G},
title = {Reproducible social phenotyping of 5xFAD mice in the Agora maze (Sociobox).},
journal = {Behavioural brain research},
volume = {},
number = {},
pages = {116327},
doi = {10.1016/j.bbr.2026.116327},
pmid = {42264393},
issn = {1872-7549},
abstract = {Neuropsychiatric (depression, schizophrenia, etc.) and neurological disorders (Alzheimer's disease, AD, Parkinson's disease) are characterized by disruptions in cognition including social interaction and recognition. Developing tools for the assessment of social behaviour in mouse models and its relevance is essential to further advance our understanding of social impairments in these diseases. In the Agora maze for rodents, stranger mice confined into cubicles around the perimeter of the open square mirror the agora (marketplace) in ancient cities. Up to 5 social interaction partners are presented and can be freely selected for interaction (exposure). In the discrimination phase one novel mouse (SNew) is presented while 4 familiar partners remain. Interaction time is recorded via video observation. In Exp 1, we validated the test with different strains of wild-type male mice (C57BL/6J, Balb/c, NMRI, PLBWT) that were able to readily identify SNew and spent significantly more time in zones adjacent to their cubicle; only NMRI mice did not prefer SNew. Exp. 2 explored 5xFAD Alzheimer mice and showed normal exploration and discrimination when aged 5 and 8 months old. Repeat of the experiment in a second cohort confirmed robustness of this phenotype, but also reproducibility of the behavioural paradigm. The Agora task allows semi-automated evaluation of preference for social novelty in a more complex paradigm by expanding the number of social interaction partners from 2 (three-chamber test) to 5 (or more), while still avoiding physical approaches and aggressive episodes. Thus, Agora provides a more physiological behavioural paradigm which is highly robust and reproducible.},
}

@article {pmid42264413,
year = {2026},
author = {Kirthiga, N and Suresh Kumar, N},
title = {A Multimodal Explainable AI Framework for Early Detection of Alzheimer's Disease Using MRI, PET, and Clinical Assessments.},
journal = {Seminars in ultrasound, CT, and MR},
volume = {},
number = {},
pages = {},
doi = {10.1053/j.sult.2026.06.009},
pmid = {42264413},
issn = {1558-5034},
abstract = {Early and accurate detection of Alzheimer's disease (AD), especially at the Mild Cognitive Impairment (MCI) stage, remains a critical challenge in clinical neurology. While deep learning models have achieved notable success in diagnosing AD using neuroimaging and clinical data, their black-box nature hin- ders trust and adoption in medical settings. This paper proposes a novel multimodal deep learning framework that integrates structural MRI, PET scans, and clinical assessments such as MMSE, APOE status, and age for AD classification. In order to combine modality- specific representations, a transformer- based fusion model is created. To improve model transparency, explainable AI (XAI) techniques are used, such as Grad-CAM for imaging data and SHAP for clinical features. Comparing the ADNI dataset to current unimodal or inexplicable models, experiments show notable gains in classification accuracy and interpretability. The suggested framework is a step toward reliable AI systems in neurology since it offers both strong predictions and therapeutically applicable insights.},
}

@article {pmid42264545,
year = {2026},
author = {Vishwakarma, H and Chauhan, A and Kaur, L and Awasthi, A},
title = {Nanotechnology-enabled targeting strategies for neurodegenerative disorders: role of functionalized nanoparticles.},
journal = {The Journal of pharmacy and pharmacology},
volume = {78},
number = {6},
pages = {},
doi = {10.1093/jpp/rgag060},
pmid = {42264545},
issn = {2042-7158},
abstract = {BACKGROUND: Neurodegenerative disorders comprise a diverse group of progressive neurological diseases characterized by the gradual loss of neuronal structure and function. Conditions such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis arise from multifactorial mechanisms involving genetic susceptibility, environmental factors, and age-related cellular decline.

PATHOPHYSIOLOGY: Key pathogenic processes include oxidative stress, mitochondrial dysfunction, protein misfolding and aggregation, impaired axonal transport, Golgi fragmentation, and chronic neuroinflammation, all of which disrupt neuronal homeostasis and synaptic communication, ultimately leading to neuronal death. Hormonal imbalances further exacerbate these effects by promoting oxidative damage, inflammation, and metabolic dysfunction.

CHALLENGES IN THERAPY: Despite advances in understanding disease mechanisms, effective drug delivery remains challenging due to the restrictive nature of the blood-brain barrier.

Recent developments highlight the potential of nanoparticle-based drug delivery systems to overcome these limitations. Functionalized nanoparticles enhance blood-brain barrier penetration, improve targeting specificity, and enable controlled drug release. These systems can deliver neuroprotective agents, antioxidants, peptides, and gene therapies directly to affected brain regions. Thus, integrating disease pathophysiology with nanotechnology-based strategies offers a promising approach for improving therapeutic outcomes and advancing precision treatment in neurodegenerative disorders.},
}

@article {pmid42264828,
year = {2026},
author = {da Silva, VP and Monteiro-Junior, RS and Moraes, H},
title = {Mind-body exercise interventions in older adults with dementia: A systematic review and meta-analysis.},
journal = {Journal of bodywork and movement therapies},
volume = {47},
number = {},
pages = {469-478},
doi = {10.1016/j.jbmt.2026.04.018},
pmid = {42264828},
issn = {1532-9283},
abstract = {OBJECTIVE: This study investigated the effects of mind-body interventions-defined as practices integrating physical movement, controlled breathing, and focused attention, such as yoga, dance, tai chi, and mindfulness-on neuropsychological and behavioural aspects in older adults with dementia.

METHODS: A systematic search was conducted in PubMed, Web of Science, Scopus, APA PsycInfo, Embase, and SciELO. Eligible studies were randomized controlled trials (RCTs) of movement-based mind-body interventions in dementia that reported at least one neuropsychological or behavioral and psychological symptom of dementia (BPSD) outcome. Physical function and quality of life were also evaluated as secondary outcomes. A meta-analysis was performed using a random-effects model, with effect sizes expressed as standardized mean differences (SMD). Heterogeneity was assessed using the I[2] statistic.

RESULTS: Eight RCTs comprising 529 participants met the inclusion criteria. Significantly large effects were observed for BPSD, particularly with mindfulness and tai chi interventions sustained for up to 1 year. Moderate improvements were also identified in neuropsychological and physical function compared with controls. No significant effects were detected for quality of life.

CONCLUSIONS: Movement-based mind-body interventions might be a cost-effective, non-pharmacological strategy to improve BPSD, neuropsychological, and physical function in individuals with dementia. However, current evidence only permits general clinical recommendations. Further large-scale, well-designed RCTs are needed to consolidate the evidence base and guide dementia care practices. This systematic review follows PRISMA-S guidelines and is registered in PROSPERO (CRD42023483823).},
}

@article {pmid42265078,
year = {2026},
author = {Ryser, T and Krichene, A and Marchi, N and Espinal, FR and Mahul-Mellier, AL and Lashuel, HA and Guiducci, C},
title = {A microfluidic platform for whole-membrane integrity profiling in live neuronal cells.},
journal = {Microsystems & nanoengineering},
volume = {12},
number = {1},
pages = {},
pmid = {42265078},
issn = {2055-7434},
support = {205321 179086//Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation)/ ; },
abstract = {Structural and functional compromise of the cellular membrane is a central mechanism in the pathogenesis of numerous diseases, including neurodegenerative disorders such as Alzheimer's and Parkinson's disease. However, existing techniques for assessing membrane integrity often lack the ability to provide dynamic, whole-cell measurements and are limited to localized damage detection or population-level analysis. There is a growing need for methods capable of monitoring membrane integrity over time at the single-cell level and across the entire membrane surface. In this study, we present a microfluidic platform for real-time, label-free assessment of membrane integrity by analyzing dielectric properties. We apply this system to investigate how different aggregated forms of α-Synuclein (aSyn), a protein that plays a central role in the pathogenesis of Parkinson's disease and disrupts neuronal membranes. Our platform integrates electrokinetic microdevices with 3D microelectrodes and imaging, enabling continuous analysis of up to 30 live neuronal cells per hour in flow. By measuring electrorotation responses, we quantify changes in plasma membrane capacitance in response to monomeric, oligomeric, and fibrillar aSyn. This approach allows direct, time-resolved comparison of membrane-disruptive effects across different aSyn conformations with single-cell resolution and whole-membrane sensitivity.},
}

@article {pmid42265098,
year = {2026},
author = {Belmont-Rausch, DM and Ludwig, MQ and Bentsen, MA and Hansen, SN and Secher, A and Holst, D and Moreno, J and Das, V and Egerod, KL and Bjerregaard, AM and Niss, K and Bau, S and Pyke, C and Dalgaard, K and Merkestein, M and Wichern, F and Hansen, CT and Polex-Wolf, J and Knudsen, LB and Pers, TH},
title = {Semaglutide attenuates neuroinflammation in male mice.},
journal = {Nature communications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41467-026-74038-4},
pmid = {42265098},
issn = {2041-1723},
support = {NNF18CC0034900//Novo Nordisk Fonden (Novo Nordisk Foundation)/ ; R190-2014-3904//Lundbeckfonden (Lundbeck Foundation)/ ; 8045-00091B//Det Frie Forskningsråd (Danish Council for Independent Research)/ ; R01 DK124238/DK/NIDDK NIH HHS/United States ; },
abstract = {Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have shown promise in preclinical models of neurodegeneration, with emerging evidence suggesting these effects may be driven by modulation of neuroinflammation. However, the cellular mechanisms underlying GLP-1RA effects on neuroinflammation remain poorly understood. Here we show, using a mouse model of lipopolysaccharide-induced neuroinflammation, how semaglutide coordinates cellular responses to resolve neuroinflammation. We find that semaglutide in male mice prevents brain infiltration of neutrophils, excessive cytokine release, and suppresses neuroinflammation-associated transcriptional signatures specifically in microglia, endothelial cells, and a subset of pericytes. Mechanistically, we identify a subset of Glp1r-expressing neurons in the dorsal vagal complex that, upon semaglutide treatment, regulate genes involved in anti-inflammatory signaling. Semaglutide-modulated pathways overlap with inflammatory signatures found in human neurodegenerative diseases, including Alzheimer's disease, suggesting broad relevance for conditions involving neuroinflammation. Together, these findings reveal how GLP-1R signaling in male mice orchestrates resolution of neuroinflammation through coordinated multi-cellular programs.},
}

@article {pmid42265203,
year = {2026},
author = {Miftakhov, R and Fortygina, P and Zuzina, A and Balaban, P and Borodinova, A},
title = {Facilitation of hippocampal long-term potentiation by astrocytic Gq signaling is compromised in an advanced Alzheimer's disease model.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-56373-0},
pmid = {42265203},
issn = {2045-2322},
support = {24-15-00149//Russian Science Foundation/ ; },
abstract = {Astrocytes communicate bidirectionally with neurons by releasing various signaling molecules. This astrocyte-neuron "dialogue" is essential for long-term processes in the nervous system, and its disruption correlates with various neuropathologies, including Alzheimer's disease (AD). Neurogenetic approaches including opto- and chemogenetics allow targeted modulation of astrocyte functioning. Our study investigated how chemogenetic activation of the Gq-coupled pathway in hippocampal astrocytes modulates synaptic plasticity and gene expression in both healthy state and AD pathology. To selectively manipulate astrocytic Gq signaling, we expressed DREADD receptors hM3Dq in hippocampal astrocytes of both wild-type (WT) and transgenic 5xFAD mice, a model of familial Alzheimer's disease, using adeno-associated viruses. In the acute brain slices, we assessed the amplitude of field excitatory postsynaptic potentials (fEPSPs) and expression of immediate early genes following activation of DREADD receptors hM3Dq via application of specific agonist Compound-21 (C21), both under resting conditions and during the induction of long-term potentiation (LTP) via theta-burst stimulation (TBS). High concentrations of C21 (2-10 µM) non-specifically increased fEPSPs amplitude even in slices lacking DREADD expression, indicating significant off-target effects. At a lower concentration (1 µM), C21 did not alter baseline synaptic transmission in mice of both genotypes. In healthy animals, chemogenetic astrocyte stimulation with C21 (1 µM) can robustly enhance activity-dependent plasticity without altering the transcription of immediate early genes. In contrast, in 5xFAD slices, the fEPSPs amplitudes were already potentiated following TBS stimulation. On this background, chemogenetic astrocyte stimulation with C21 (1 µM) elicited no further increase in LTP. Our work highlights a common pitfall in chemogenetic studies by demonstrating that excessive DREADD agonist concentrations (more than 1 µM) produce significant off-target effects. We further show that stimulation of astrocytic Gq signaling with low agonist concentration exerts a facilitation of long-term hippocampal plasticity in slices from healthy animals. However, the efficacy of targeted astrocytic Gq-mediated modulation appears limited in advanced-stage AD. LTP was enhanced and C21 did not facilitate it further, likely due to a significant reorganization of neuroglial communications.},
}

@article {pmid42265278,
year = {2026},
author = {Li, Z and Che, T and Yan, S and Wang, D and Liu, Y and Zhao, K},
title = {Forecasting Alzheimer's disease progression via identity-preserved denoising diffusion generative adversarial network.},
journal = {NPJ digital medicine},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41746-026-02865-2},
pmid = {42265278},
issn = {2398-6352},
support = {No. CX2023117//BUPT Excellent Ph.D. Students Foundation/ ; No. T2425027//National Natural Science Foundation of China/ ; No. 82401858//National Natural Science Foundation of China/ ; No. 7244519//Beijing Municipal Natural Science Foundation/ ; },
abstract = {Forecasting the progression of Alzheimer's disease (AD) is essential for evaluating secondary prevention measures thought to modify the disease trajectory. However, accurate prediction of longitudinal MRIs remains challenging, particularly in preserving subject identity, as deep generative models may potentially generate plausible future MRIs of different individuals from a single baseline scan. In the present study, we developed a novel identity-preserved denoising diffusion generative adversarial network (IP-DDGAN) capable of rapidly generating subject-specific longitudinal MRIs conditioned on metadata. Concretely, we developed an identity-preservation strategy incorporating a metadata-guided module and identity-preserved regularization terms to maintain subject identity in synthetic longitudinal MRIs. Furthermore, we comprehensively integrated morphometric, subject-identity-consistency, and image-level quality metrics to evaluate the fidelity and biological plausibility of synthetic longitudinal MRIs. The results demonstrate that the synthetic MRIs generated by IP-DDGAN retain biological and disease-related phenotypes and exhibit sufficient realism to support downstream applications. Our proposed model effectively captures temporal biological and disease-related changes and predicts distinct disease progression trajectories, including the clinically important transitions from cognitively normal (CN) to mild cognitive impairment (MCI) and from MCI to AD.},
}

@article {pmid42265282,
year = {2026},
author = {Sanati, S and Rahimi, E and Hodtani, GA and Eslami, S},
title = {An information-theoretic evaluation framework for CNN-LSTM-based Alzheimer's disease classification from structural MRI.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-56939-y},
pmid = {42265282},
issn = {2045-2322},
abstract = {Early detection of Alzheimer's disease (AD) is important because of its progressive impact on cognitive function. This study presents a CNN-LSTM-based framework for three-class AD classification from structural MRI, with the primary contribution being a post-hoc information-theoretic evaluation strategy rather than a new network architecture. Experiments were conducted using 827 ADNI subjects, including normal controls (NC: 340), mild cognitive impairment (MCI: 307), and AD (180). To mitigate data scarcity and improve training diversity, GAN-based augmentation was applied only to the training data, while validation and test subjects were kept separate. In addition to conventional metrics, trained models were evaluated using Renyi mutual information, Renyi divergence, and Henze-Penrose divergence to quantify information preservation, representation stability, and distributional alignment. Under a subject-level evaluation protocol, the CNN-LSTM model achieved 96.7% accuracy and outperformed evaluated benchmark architectures under the same protocol. The information-theoretic measures provided complementary evidence for comparing model behavior beyond accuracy, particularly regarding information retention and output-distribution alignment. Overall, the findings suggest that post-hoc information-theoretic analysis can support more transparent assessment of MRI-based AD classification models. However, external validation on independent multi-center datasets is required before clinical deployment can be considered.},
}

@article {pmid42265349,
year = {2026},
author = {Arunachalam, P and Pieperhoff, L and Lorenzini, L and Tranfa, M and Masserini, F and Treves, F and Pontillo, G and Preti, MG and Broeders, TAA and Schoonheim, MM and Douw, L and Ritchie, C and Boada, M and Marquié, M and Visser, PJ and Cacciaglia, R and Gispert, JD and Salvadó, G and Luckett, ES and Collij, LE and Cole, JH and Barkhof, F and Wink, AM and , },
title = {Decreased amyloid-related structure-function coupling in preclinical Alzheimer's disease.},
journal = {Communications medicine},
volume = {},
number = {},
pages = {},
doi = {10.1038/s43856-026-01707-2},
pmid = {42265349},
issn = {2730-664X},
support = {WE.03-2023-14//Alzheimer Nederland (Alzheimer Netherlands)/ ; 115952//European Federation of Pharmaceutical Industries and Associations (EFPIA)/ ; 115736//European Federation of Pharmaceutical Industries and Associations (EFPIA)/ ; SG-21-818099/ALZ/Alzheimer's Association/United States ; },
abstract = {BACKGROUND: Structural pathways of the brain facilitate functional communication, and their disruption in preclinical Alzheimer's disease may reflect network vulnerability and compensatory brain maintenance. However, it remains unclear how early amyloid-β affects structure-function alignment, whether effects are explained by functional network organisation, how they relate to cognition, and which biological processes contribute to their development.

METHODS: We included 460 older adults without dementia from AMYPAD-PNHS with functional MRI, diffusion MRI, and amyloid-β PET. Structure-function coupling was quantified using the structural-decoupling index (SDI) at global, sub-network, and regional scales. Linear models investigated the effect of amyloid-β burden on SDI. Mediation analyses evaluated whether functional graph topology explained amyloid-associated SDI effects and whether SDI mediated the relationship between amyloid-β burden and cognition. Regional gene expression data were integrated to assess transcriptomic determinants of amyloid-related structure-function coupling.

RESULTS: Amyloid-positive individuals exhibit higher global SDI, driven by visual cortices. Mediation analyses demonstrate that amyloid-related SDI alterations are explained by reductions in local clustering, indicating less segregated processing. Despite higher SDI in amyloid-positive individuals, elevated SDI in visual regions mitigates the negative effect of amyloid-β burden on cognition. Amyloid-related SDI changes correlate with genes associated with amyloid-β metabolism, microglial activation, and synaptic remodelling.

CONCLUSIONS: Early amyloid-β pathology is associated with decoupling of brain structure and function, primarily in visual cortices, mediated by network reconfiguration and shaped by regional molecular architecture. These findings suggest that lower structure-function coupling may represent a compensatory mechanism in preclinical Alzheimer's disease and highlight SDI as a biomarker for stratification and monitoring in prevention trials.},
}

@article {pmid42265376,
year = {2026},
author = {Sanda, N and Milea, D and Kovari, E and Tong, Y and Cella, A and Brügger, T and Hannibal, J and Egervari, KL and Lobrinus, JA and Carrera, E and Thumann, G and Kleinlogel, S and Adamantidis, A and Mure, LS},
title = {Functional and morphological alterations of light detection circuits in postmortem retina from donors with different stages of Alzheimer's-like pathology.},
journal = {Communications biology},
volume = {},
number = {},
pages = {},
doi = {10.1038/s42003-026-10465-9},
pmid = {42265376},
issn = {2399-3642},
support = {1429//Velux Stiftung (Velux Foundation)/ ; 1429//Velux Stiftung (Velux Foundation)/ ; },
abstract = {Disruption of sleep and circadian rhythms is one of the earliest symptoms of Alzheimer's disease (AD). Circadian entrainment and modulation of alertness are non-visual responses to light driven by intrinsically photosensitive retinal ganglion cells (ipRGCs). To explore structural and functional changes of ipRGCs and ipRGC circuits in AD, we analyzed the retinas and brains of 13 elderly patients ranging from normal cognition to AD and performed ex vivo extracellular electrophysiological recordings on freshly harvested retinas. While no impairment of rods and cones was observed, there was a severe loss of ipRGCs in AD donors. Importantly, the remaining ipRGCs exhibited morphological alterations, hyperexcitability, and were not able to sustain high levels of activation. These changes may be ipRGC subtype-specific and vary across donors with pathological severity. Altered ipRGC circuits and function could contribute to the disruption of sleep and circadian rhythms reported in AD patients. Measuring ipRGC-dependent responses to light could be a promising way to predict or monitor pathological changes in the brain.},
}

@article {pmid42265387,
year = {2026},
author = {Kizuka, Y},
title = {Rise in sugar decoration in Alzheimer's disease.},
journal = {Nature metabolism},
volume = {},
number = {},
pages = {},
pmid = {42265387},
issn = {2522-5812},
}

@article {pmid42265388,
year = {2026},
author = {Hawkinson, TR and Liu, Z and Ribas, RA and Medina, T and Nielsen, RS and Clarke, HA and Ma, X and Mueller, AC and Plasencia, AF and Sheer, AL and Simpson, ST and Soto, CM and Sudderth, J and Cai, F and Cantrell, AR and Colpaert, MG and Shedlock, CJ and Wu, L and Young, LEA and Kooser, DD and Chen, L and Ryan, AM and Quinones, S and Son, J and Azadi, P and Deberardinis, RJ and Prokop, S and Allison, D and Yang, S and Chen, H and Huang, Y and He, X and Alonge, KM and Guo, J and Guo, Y and Bian, J and Vander Kooi, CW and Gentry, MS and Sun, RC},
title = {Hyperglycosylation is a metabolic driver of Alzheimer's disease.},
journal = {Nature metabolism},
volume = {},
number = {},
pages = {},
pmid = {42265388},
issn = {2522-5812},
abstract = {Alzheimer's disease (AD) is a devastating neurodegenerative disorder marked by progressive cognitive decline. Metabolic disruptions are widely observed, yet their involvement in the molecular aetiology of AD remains underexplored. Here we identify hyperglycosylation as a driver of AD. Integrating spatial metabolomics, lipidomics and glycomics in transgenic AD mouse models and post-mortem human AD samples, along with advanced spatial isotopic tracing pulse-chase analysis of N-linked glycans, we demonstrate that the conserved phenotype of brain hyperglycosylation is driven by increased glycan biosynthesis. Genetic knockdown of glycan biosynthetic enzymes improves cognitive outcomes in AD mice whereas oral glucosamine supplementation impairs them. A retrospective analysis of electronic health records from patients with AD with varying disease severity shows that glucosamine supplementation is associated with accelerated AD progression and worsened survival. Overall, these results establish hyperglycosylation as a pathological driver of AD and highlight glycan metabolism as an actionable target in the fight against AD.},
}

@article {pmid42265465,
year = {2026},
author = {Dhingra, P and Kumar, A and Raj, PM and Patel, P and Sahu, KK and Das Kurmi, B},
title = {Salivary protein macromolecules as diagnostic and therapeutic biomarkers linking oral health and neurodegenerative diseases-emerging mechanisms and future perspectives.},
journal = {Inflammopharmacology},
volume = {},
number = {},
pages = {},
pmid = {42265465},
issn = {1568-5608},
abstract = {Oral diseases and neurodegenerative diseases represent two overlapping global health challenges, driven by shared risk factors and the rapid ageing of the population. Emerging evidence suggests that the oral-brain axis functions as a critical mechanistic link between these conditions. Chronic oral dysbiosis, particularly periodontitis, can induce systemic inflammation, disrupt the blood-brain barrier, and promote neuroinflammation, a hallmark of neurodegenerative diseases. Saliva, a non-invasive and easily accessible biofluid, provides valuable insights into both oral and systemic health. This review presents current evidence on the role of salivary protein macromolecules as diagnostic and therapeutic tools within the framework of the oral-brain axis. Key biomarkers, including α-synuclein in Parkinson's disease and amyloid-β and tau proteins in Alzheimer's disease, are highlighted for their diagnostic potential. Furthermore, emerging therapeutic strategies are discussed, including oral health interventions, targeted pharmacological approaches, and the use of salivary proteins and exosomes in regenerative medicine and drug delivery. Advances in analytical technologies, such as mass spectrometry and bioinformatics, are also examined, along with the challenges associated with standardization and clinical validation. Overall, salivaomics represents a promising approach for the early diagnosis, prevention, and management of neurodegenerative diseases through non-invasive biomarker profiling and multi-omics integration.},
}

@article {pmid42265487,
year = {2026},
author = {Charemis, D and Lampropoulos, D and Dimakopoulos, Y and Sivolapenko, G and Hadjinicolaou, M},
title = {Dead-Space Microdomains as Explicit Barriers to Extracellular Drug Transport in Alzheimer's Disease.},
journal = {Pharmaceutical research},
volume = {},
number = {},
pages = {},
pmid = {42265487},
issn = {1573-904X},
support = {80720//Special Account for Research Funds, Hellenic Open University/ ; 80720//Special Account for Research Funds, Hellenic Open University/ ; 80720//Special Account for Research Funds, Hellenic Open University/ ; },
abstract = {OBJECTIVE: The impact of dead-space (DS) microdomains on cerebral drug penetration has been demonstrated experimentally; yet computational models typically capture their effects indirectly through effective tortuosity parameters. Here, we develop an anatomically grounded framework that systematically evaluates pharmaceutical diffusion within the central nervous system (CNS).

METHODS: A finite element (FE) model was developed with DS explicitly represented as impermeable obstructions in the extracellular space (ECS) - consistent with structural remodeling observed in Alzheimer's disease (AD). The model was calibrated by reproducing experimental diffusion timescales and subsequently applied to quantify the geometric contribution of DS to pharmaceutical transport.

RESULTS: Transport hindrance exhibited a strong dependence on molecular size. Within a representative ECS unit, the arrival of the 0.5 c 0 concentration contour at the venule was delayed by 11 s for Memantine, 14 s for Donepezil, and 80 s for Aducanumab. Spatial analyses revealed penetration delays that were not captured by domain-averaged uptake metrics. A Péclet number analysis confirmed that ECS transport for all three compounds remains diffusion-dominated under neurodegenerative conditions.

CONCLUSIONS: The proposed framework provides a computationally efficient foundation for predictive multiphysics modeling in the human CNS and demonstrates how local ECS obstructions can lead to therapeutic hindrance in AD.},
}

@article {pmid42265577,
year = {2026},
author = {Nega, C and Beratis, IN and Moustaka, K and Kourtesis, P},
title = {A latent variable approach to multifactorial associations with sleep problems in individuals with mild cognitive impairment.},
journal = {Aging & mental health},
volume = {},
number = {},
pages = {1-12},
doi = {10.1080/13607863.2026.2683909},
pmid = {42265577},
issn = {1364-6915},
abstract = {BACKGROUND: This study examines key associations of psychological symptoms, cognitive functioning, and age of onset with sleep problems, especially insomnia, in individuals with mild cognitive impairment (MCI), using a latent-variable approach.

METHODS: A total of 127 Greek individuals with MCI, consecutive visitors of an Alzheimer's day clinic, underwent comprehensive assessments of cognitive functioning, psychological symptoms, and sleep disturbances. The model was examined using a Partial Least Squares approach to structural equation modeling, incorporating three latent constructs: 'psychological burden' (depressive symptoms, anxiety, and stress), 'cognitive status' (general cognition, phonemic and semantic fluency, executive functioning/mental flexibility, and episodic memory), and 'sleep problems' (nocturnal awakenings, early awakenings, insufficient duration, impaired daytime functioning, and reduced well-being).

RESULTS: The model demonstrated acceptable fit, predictive relevance, and superior predictive performance compared to linear regression. 'Psychological burden' was the strongest predictor of sleep problems, whereas 'cognitive status' showed a significant negative association, with lower cognitive abilities linked to greater sleep disturbances. Earlier MCI onset was also associated with more severe sleep problems.

CONCLUSION: The latent-variable approach revealed the multidimensional complexity of sleep problems in MCI, highlighting the need for integrative evaluations and interventions that target cognitive status and psychological well-being as clinically relevant targets for assessment and management.},
}

@article {pmid42265698,
year = {2026},
author = {Delva, A and Joza, S and Tremblay, C and Vo, A and Filiatrault, M and Carrier, M and Taylor, JP and O'Brien, JT and Firbank, M and Thomas, A and Donaghy, PC and Camicioli, R and Chertkow, H and Dagher, A and Postuma, RB and Rahayel, S},
title = {Selective molecular and network architecture features underlie brain cortical atrophy in dementia with Lewy bodies.},
journal = {Journal of biomedical science},
volume = {33},
number = {1},
pages = {},
pmid = {42265698},
issn = {1423-0127},
support = {PPG-2023-0000000122//Parkinson Canada/ ; 0000000082//Alzheimer Society/ ; MJFF-025745//Michael J. Fox Foundation for Parkinson's Research/ ; },
abstract = {BACKGROUND: Dementia with Lewy bodies shares clinical and pathological features with both Parkinson's disease and Alzheimer's disease, but the local biological factors that render specific cortical regions vulnerable to atrophy remain poorly defined. In particular, it is unclear whether cortical thinning in dementia with Lewy bodies reflects generic neurodegenerative mechanisms, processes shared with Parkinson's disease and Alzheimer's disease, or dementia with Lewy bodies-specific molecular and network susceptibilities.

METHODS: A total of 89 patients with dementia with Lewy bodies and 89 matched controls underwent T1-weighted brain MRI. Scans were processed to generate surface-based cortical thickness maps. Regional cortical thickness estimates, after slice-by-slice manual correction, were mapped to gene expression data from healthy postmortem human brains to identify transcriptomic signatures associated with decreased thickness in dementia with Lewy bodies. We assessed whether genes whose expression was increased with regional thinning converged onto established Parkinson's disease- and Alzheimer's disease-related pathways and identified genes uniquely implicated in dementia with Lewy bodies. Spatial annotation mapping was then used to test whether patterns of cortical thinning overlapped with in vivo neurotransmitter system distributions and whether the observed thickness pattern was constrained by large-scale structural connectivity, consistent with a network-based propagation process.

RESULTS: Cortical thinning predominated in regions that, in the healthy brain, show higher expression of genes involved in mitochondrial function and synaptic transmission. The transcriptomic profile associated with thinning significantly overlapped with genes belonging to Parkinson's disease and Alzheimer's disease pathways, supporting shared pathogenic mechanisms across Lewy body- and Alzheimer-type neurodegeneration. However, 90 genes associated with cortical thinning did not overlap with Parkinson's disease or Alzheimer's disease pathways and were enriched for GABAergic signalling. Spatial mapping analyses showed that regions with greatest thickness reductions colocalized with GABAA, serotoninergic 5-HT1A, 5-HT1B, 5-HT4, and dopaminergic D2 receptor distributions, and that the thickness pattern followed structural connectivity.

CONCLUSIONS: MRI-derived cortical thickness changes in dementia with Lewy bodies reflect selective molecular and network vulnerabilities rather than a non-specific degenerative process. Mitochondrial and synaptic genes, together with a distinct GABAergic association and connectivity constraints, delineate mechanisms explaining why some cortical territories are more affected in dementia with Lewy bodies.},
}

@article {pmid42265753,
year = {2026},
author = {Candlish, M and Hofmann, J and Brösamle, D and Haessler, A and DeMeglio, M and Skodras, A and Tushev, G and De Biasi, ES and Günther, S and Wiegandt, R and Theis, H and De Domenico, E and Hermann, NS and Breunig, P and Sauerland, C and Nilsson, KPR and Beyer, MD and Looso, M and Windbergs, M and Roeber, S and Herms, J and Neher, JJ and Chiocchetti, AG and Hefendehl, JK},
title = {Ischemic injury triggers a protective microglial phenotype in models of Aβ pathology.},
journal = {Journal of neuroinflammation},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12974-026-03897-x},
pmid = {42265753},
issn = {1742-2094},
abstract = {Microglia are highly plastic cells that are capable of integrating subsequent insults. As the majority of Alzheimer's Disease (AD) patients also show cerebrovascular pathology, we here aimed to dissect the interactions between AD and ischemic brain injury on the microglial response to amyloid beta (Aβ) pathology. Unexpectedly, ischemic stroke in the context of cerebral β-amyloidosis drives the emergence of a neuroprotective microglial phenotype characterized by an ApoE-enriched transcriptional state and enhanced lipid handling. These microglia promote the rapid formation of highly compact Aβ plaques that are relatively inert and strikingly reminiscent of those observed in cognitively resilient AD patients. Our findings thus reveal that the microglial response to Aβ pathology is not a fixed trajectory toward dysfunction, but retains a capacity for beneficial reprogramming when engaged by the appropriate stimulus. Beyond characterizing this comorbid state, our data identify specific molecular pathways, centered on ApoE, complement activation, and lysosomal processing, that may be amenable to therapeutic targeting to promote protective microglial function in AD.},
}

@article {pmid42265757,
year = {2026},
author = {Kuilman, MM and Ahmad, S and Pomp, AC and Wolters, FJ and Kaddurah-Daouk, R and Ikram, MA and Ghanbari, M},
title = {Associations of plasma metabolites with protein biomarkers linked to Alzheimer's disease pathology in the Rotterdam Study.},
journal = {Alzheimer's research & therapy},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13195-026-02108-2},
pmid = {42265757},
issn = {1758-9193},
support = {GA N° 101095426//Nederlandse Organisatie voor Wetenschappelijk Onderzoek/ ; },
abstract = {BACKGROUND: Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder characterized by amyloid-β (Aβ) and tau pathology, neuroaxonal damage, and neuroinflammation. While blood biomarkers, such as tau, neurofilament light chain (NfL), and Aβ isoforms, reflect AD pathology, the systemic metabolic alterations contributing to the disease remain poorly defined. This study aims to explore associations between plasma metabolites and key protein biomarkers linked to AD pathology in a large, population-based cohort.

METHODS: Plasma levels of Aβ40, Aβ42, total-tau (t-tau), and NfL were measured using the highly sensitive Simoa NF-light and N3PA assays (Quanterix platform) among over 3,000 participants from the Rotterdam Study. Plasma metabolites were quantified using the Nightingale NMR-based (n = 2,871) and Metabolon MS-based (n = 1,491) platforms. Multivariable linear regression models, adjusted for demographic, lifestyle, and genetic factors, were applied. Analyses were stratified by sex and APOE genotype. Sensitivity analyses excluded participants with dementia, stroke, or impaired kidney function.

RESULTS: Triglyceride-rich lipoproteins across VLDL, LDL, and HDL subclasses were positively associated with both Aβ isoforms. Among them, Triglyceride-rich lipoproteins in small VLDL showed the strongest association with Aβ40 (β = 0.168, FDR = 4.362e-16). Conversely, HDL cholesterol fractions showed inverse associations with Aβ. GlycA (β > 0.097, FDR < 2.092e-05) and creatinine (β > 0.253, FDR < 3.371e-24) were positively associated with all Alzheimer's disease biomarkers, while albumin was inversely related to tau (β = -0.094, FDR = 1.924e-04) and NfL (β = -0.079, FDR = 4.210e-05). On the Metabolon platform, S-adenosylhomocysteine (β > 0.206, FDR < 1.303e-09) was positively associated with all biomarkers, while uridine and 2'-deoxyuridine showed inverse associations with Aβ40, t-tau, and NfL. Stratified analyses indicated stronger GlycA-tau associations in APOE ε2 carriers and sex-specific effects for amino acids and ApoA1.

CONCLUSIONS: Our findings highlight metabolites involved in lipid transport, inflammation, amino acid metabolism, and methylation as being linked to AD-related protein biomarkers. These results provide novel insights into systemic metabolic pathways underlying AD and suggest that certain metabolites may serve as potential biomarkers for early detection and risk stratification in AD.},
}

@article {pmid42265779,
year = {2026},
author = {Bouteloup, V and Proust-Lima, C and Pellegrin, I and Boizard-Moracchini, A and Roy, M and Chêne, G and Planche, V and Dufouil, C and , },
title = {Methodological approaches to account for assay changes in longitudinal biomarker analysis: insights from Alzheimer's blood biomarkers in the MEMENTO cohort.},
journal = {Alzheimer's research & therapy},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13195-026-02042-3},
pmid = {42265779},
issn = {1758-9193},
abstract = {BACKGROUND: Longitudinal studies allow the modelling of disease progression through repeated measurement of health outcomes, such as biomarkers. Changes in measurement tools over time, due to logistical or financial constraints, may challenge the statistical modeling of outcome trajectories. This study aims to compare two methods for managing changes in blood biomarkers assays over time, in the context of modeling their longitudinal trajectories.

METHODS: We analyzed data from 2299 individuals in the French MEMENTO cohort, focusing on two Alzheimer's disease blood biomarkers: 181-phosphorylated tau (p-tau181) and neurofilament light chain (NfL). Baseline blood samples were quantified using an initial assay kit in 2021, while samples collected at 2- and 4-year follow-ups with updated kits in 2023. Two approaches were applied to derive conversion equations for aligning measurements from the initial to the updated assay: (i) a bridging study, requiring biomarker quantification using both the initial and the updated assay in a subsample of individuals and (ii) Latent Process Models (LPM), which established links between the two assays as measures of the same latent process over age, using biomarker measurements available at the 3 timepoints. Prediction error rates were computed, and biomarker trajectories estimated with linear mixed models according to two variables of interest (education level, cognitive impairment).

RESULTS: Prediction error rates were slightly higher for LPM than for bridging for both NfL and p-tau181. While the two methods yielded similar predictions around the median, discrepancies were observed at the tails of the distribution of the observed values. Longitudinal trajectories showed consistent associations for the variables of interest at baseline and during follow-up for both biomarkers.

CONCLUSIONS: LPM provide a feasible and efficient method for managing changes in biomarker quantification assays in longitudinal studies. LPM yields results comparable to traditional bridging studies without requiring additional sample analysis. This approach is particularly advantageous in studies with long-term follow-up, where changes in measurement tools cannot always be avoided, offering a straightforward and resource-efficient solution.},
}

@article {pmid42265789,
year = {2026},
author = {Barlis, KL and Horner, MD and Mintzer, J and Back, SE and Lawson, A and Crull, J and Yaffe, K and Absher, J and Brawman-Mintzer, O and Joseph, JE},
title = {Verbal Memory in Traumatic Brain Injury: Associations With Age, Post-traumatic Stress Disorder, and Antidepressant Use.},
journal = {The Journal of head trauma rehabilitation},
volume = {},
number = {},
pages = {},
pmid = {42265789},
issn = {1550-509X},
support = {W81XWH-18-1-0816//U.S. Department of Defense/ ; R01 AG055132/AG/NIA NIH HHS/United States ; },
abstract = {OBJECTIVE: Episodic memory is one of the cognitive domains most affected after a traumatic brain injury (TBI), and memory decline is a hallmark of both normal aging and Alzheimer disease (AD). Although TBI is reported to accelerate age-related cognitive decline and brain atrophy, it is unclear how this trajectory is shaped by frequent co-occurring factors such as post-traumatic stress disorder (PTSD) and psychotropic medication use. This study tested whether age-related decline in delayed verbal memory is more pronounced among adults with a history of TBI than those without TBI. Analyses also explored PTSD status and use of selective serotonin reuptake inhibitors or serotonin-norepinephrine reuptake inhibitors (SSRIs/SNRIs) as independent moderators of verbal memory performance.

SETTING: VA Medical Center and surrounding community.

PARTICIPANTS: Sixty-two Veterans and civilians, ages 30-65, were enrolled. Participants who performed below established cutoffs on performance validity testing were excluded. Analyses (n = 56) included 28 adults with a history of TBI (82% mild, 18% moderate) and 28 demographically matched controls without TBI.

MAIN MEASURES: Delayed recall on a standardized verbal memory task was the primary outcome measure. Analyses tested for main effects of TBI status, age, and their interaction, as well as interactions with the moderator variables (PTSD status and SSRI/SNRI use).

DESIGN: Observational, cross-sectional design.

RESULTS: Participants with a TBI history did not significantly differ from those without TBI in verbal memory performance. There was a trend toward poorer memory performance with age among participants with a TBI history not taking SSRIs/SNRIs, while participants with PTSD and TBI taking SSRIs/SNRIs demonstrated better performance with age.

CONCLUSION: The findings underscore the importance of considering psychiatric comorbidities and medication use when examining cognition and aging effects in individuals with TBI. Larger, longitudinal studies are warranted to clarify how traumatic stress and psychotropic medications may mediate cognitive aging trajectories after TBI.},
}

@article {pmid42265832,
year = {2026},
author = {Benito-León, J and Benito-Rodríguez, CM},
title = {Digital eye tracking and plasma biomarkers: Distinguishing functional cognitive impairment from Alzheimer's disease biology.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {6},
pages = {e71575},
doi = {10.1002/alz.71575},
pmid = {42265832},
issn = {1552-5279},
}

@article {pmid42265834,
year = {2026},
author = {Ling, Y and Sun, P and Guo, T and Luo, B},
title = {"Digital eye tracking and plasma biomarkers: Distinguishing functional cognitive impairment from Alzheimer's disease biology".},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {6},
pages = {e71574},
doi = {10.1002/alz.71574},
pmid = {42265834},
issn = {1552-5279},
support = {2022C03064//the key Research and Development Program of Zhejiang/ ; 2025ZFJH01//the Fundamental Research for the Central Universities/ ; 2022KY067//Medical and Health Science and Technology Project of Zhejiang Province/ ; 82422027//National Natural Science Foundation of China/ ; U24A20340//National Natural Science Foundation of China/ ; },
}

@article {pmid42265841,
year = {2026},
author = {Wu, J and Oishi, K and Soldan, A and Pettigrew, C and Lin, Z and Zhu, Y and Jiang, D and Li, X and Gou, Y and Moghekar, A and Liu, P and Bakker, A and Oishi, K and Albert, M and Lu, H},
title = {Five-year change in brain metabolism across the spectrum of cognitive impairment in older adults: a quantitative MRI study.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {6},
pages = {e71561},
doi = {10.1002/alz.71561},
pmid = {42265841},
issn = {1552-5279},
support = {U19 AG033655/NH/NIH HHS/United States ; R21 AG055153/NH/NIH HHS/United States ; R01 AG091312/NH/NIH HHS/United States ; R01 AG085299/NH/NIH HHS/United States ; R01 AG064792/NH/NIH HHS/United States ; R01 AG071515/NH/NIH HHS/United States ; R01 NS106711/NH/NIH HHS/United States ; R01 NS106702/NH/NIH HHS/United States ; P41 EB031771/NH/NIH HHS/United States ; S10 OD021648/NH/NIH HHS/United States ; },
abstract = {INTRODUCTION: It is desirable to measure brain metabolism without needing ionizing radiation and elucidate its time trajectory. This study employed a positron emission tomography -validated, non-invasive magnetic resonance imaging (MRI) technique to characterize longitudinal changes in cerebral metabolic rate of oxygen (CMRO2) in both cognitively normal and impaired older adults.

METHODS: Participants received serial MRI-based CMRO2 scans between 2015 and 2025. Levels of AD pathology were measured in cerebrospinal fluid and plasma at the initial MRI.

RESULTS: At the initial visit, participants with MCI/dementia had lower CMRO2 than normal participants. In the longitudinal analyses, CMRO2 decreased over time in those who were cognitively impaired but remained unchanged in normals. Among normal participants, higher initial levels of total tau and phosphorylated tau at threonine 181 were associated with an increase in CMRO2 during follow-up, especially in amyloid-positive individuals.

DISCUSSION: Aside from the well-known metabolic slowdown in the later phases of AD, the brain exhibits tau-dependent hypermetabolism during the preclinical stage.},
}

@article {pmid42266046,
year = {2026},
author = {Luo, Z and Lin, F and Xu, H and Huang, Z and Weng, X and Liu, L and Chen, Y and Qu, J},
title = {In Vivo Hyperspectral CARS Imaging Reveals Photobiomodulation-Driven Remodeling of Fatty Acid Homeostasis in an AD Mouse Model.},
journal = {Analytical chemistry},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.analchem.6c01421},
pmid = {42266046},
issn = {1520-6882},
abstract = {Alzheimer's disease (AD) is increasingly acknowledged to be associated with early lipid metabolic dysfunction. However, the exact timing and mechanism of the emergence, in vivo organization, and response to therapeutic intervention of fatty-acid saturation imbalance in the living brain remain unclear. In this study, a longitudinal in vivo hyperspectral coherent anti-Stokes Raman scattering (CARS) microscopy platform, integrated with multivariate curve resolution (MCR), was established to enable label-free phenotyping of fatty-acid composition in the cortex of APP/PS1 mice. Hyperspectral CARS imaging reveals abundant lipid-droplet deposition at early stages, followed by a gradual enhancement of saturated-fat-associated vibrational signatures and a distinct plaque-centric spatial redistribution around amyloid deposits. The unmixing results are verified by liquid chromatography-mass spectrometry, which identifies palmitic acid and stearic acid as the major saturated lipid species enriched within pathological droplets. Through the application of a photobiomodulation (PBM) regimen (transcranial 808 nm, 40 Hz), it is demonstrated that PBM significantly alleviates saturated-rich lipid accumulation adjacent to plaques and cerebral vessels, restores the balance between saturated and unsaturated fatty acids, and is accompanied by improved cognitive performance. Collectively, this research establishes an imaging-based framework to elucidate in vivo lipid-metabolic remodeling during AD progression and to quantitatively evaluate metabolic reprogramming induced by PBM-based intervention.},
}

@article {pmid42266137,
year = {2026},
author = {Wu, Q and Hui, X and Cui, A and Meng, X},
title = {Harnessing the Ocean's Power: Fucoidan as a Novel Neuroregenerative Agent.},
journal = {Drug development research},
volume = {87},
number = {4},
pages = {e70331},
doi = {10.1002/ddr.70331},
pmid = {42266137},
issn = {1098-2299},
abstract = {Neurological disorders, characterized by progressive neuronal loss and functional decline, pose a formidable challenge to global health due to the lack of effective therapies. Fucoidan, a class of fucose-rich sulfated polysaccharides derived from brown seaweed, has emerged as a highly promising candidate for neuronal regeneration. This review synthesizes the extensive body of preclinical evidence supporting the neuroprotective and neuroregenerative potential of fucoidan. Its therapeutic efficacy relies on potent anti-inflammatory activity through the modulation of glial cell activation, significant antioxidant effects by neutralizing reactive oxygen species and reinforcing endogenous defenses, and direct anti-apoptotic actions that inhibit programmed cell death. Furthermore, this review highlights the pivotal and emerging role of the microbiota-gut-brain axis as a key regulator of the neuroprotective effects of fucoidan, whereby its prebiotic activity in the gut instigates systemic benefits that extend to the central nervous system. By consolidating findings from diverse preclinical models of ischemic stroke, traumatic brain injury, Alzheimer's disease, and Parkinson's disease, we conclude that fucoidan is a powerful, multitarget agent. Future research focused on establishing precise structure-activity relationships and further elucidating its action via the gut-brain axis will be important for translating this promising natural compound into a validated clinical therapy for neurological disorders.},
}

@article {pmid42266204,
year = {2026},
author = {Yang, KL and Ma, Y and Ennis, G and Jonaitis, E and Reyes, RER and Johnson, SC and Ashton, NJ and Blennow, K and Zetterberg, H and Bendlin, BB},
title = {Metabolic and renal factors associated with plasma phosphorylated tau analytes used to detect Alzheimer's disease pathology.},
journal = {Alzheimer's & dementia (Amsterdam, Netherlands)},
volume = {18},
number = {2},
pages = {e70383},
pmid = {42266204},
issn = {2352-8729},
abstract = {INTRODUCTION: We examined the extent to which insulin resistance (IR), type 2 diabetes mellitus, obesity, and kidney function are associated with plasma phosphorylated tau (p-tau) concentrations (p-tau181, p-tau217, p-tau231) in the same cohort and the contribution of these factors on amyloid positron emission tomography (PET) concordance and longitudinal p-tau levels.

METHODS: We analyzed data from 287 participants using partial Spearman rho, Mann-Whitney U, receiver operating characteristic analysis, and linear mixed models.

RESULTS: Concordance between plasma p-tau217 and amyloid PET was not influenced by IR or estimated glomerular filtration rate (eGFR). Accounting for eGFR improved concordance of p-tau181 and p-tau231 with amyloid PET. Age, binarized waist-to-hip ratio, and amyloid status were associated with all longitudinal p-tau concentrations, and eGFR associated with longitudinal p-tau231.

DISCUSSION: Metabolic factors may influence the interpretation of longitudinal plasma p-tau concentrations and kidney function may influence amyloid PET concordance for p-tau181 and p-tau231, potentially necessitating analyte-specific adjustments or considerations in clinical interpretation.},
}

@article {pmid42266233,
year = {2026},
author = {Chen, Z and Zhang, Y and Zhu, X and Wu, H and Yu, T and Liu, Z},
title = {Comparative efficacy of exercise interventions on depressive symptoms and related outcomes in patients with Alzheimer's disease, cognitive impairment, and Parkinson's disease: a systematic review and network meta-analysis.},
journal = {Frontiers in physiology},
volume = {17},
number = {},
pages = {1825740},
pmid = {42266233},
issn = {1664-042X},
abstract = {BACKGROUND: Patients with Alzheimer's disease, cognitive impairment, and Parkinson's disease often experience depressive symptoms, which negatively impact quality of life and disease management. Exercise is an important non-pharmacological treatment in these populations; however, the relative efficacy of different exercise modalities remains unclear. This study used a systematic review and network meta-analysis to compare the effects of various exercise interventions on depressive symptoms and related outcomes.

METHODS: We systematically searched Chinese and English databases for randomized controlled trials evaluating exercise interventions in patients with Alzheimer's disease, cognitive impairment (including mild cognitive impairment and dementia), and Parkinson's disease. The primary outcome was depressive symptoms, assessed by using Geriatric Depression Scale (GDS) and Beck Depression Inventory (BDI); the secondary outcomes were cognitive function and motor function, assessed by using Mini-Mental State Examination (MMSE) and Unified Parkinson's Disease Rating Scale Part III (UPDRS III), respectively. Network meta-analysis was performed using Stata 16.0, and supplementary pairwise meta-analyses by disease type were conducted for the primary outcomes. RevMan 5.4 was used to assess the risk of bias, and the CINeMA framework was used to evaluate the credibility of the evidence.

RESULTS: A total of 23 randomized controlled trials involving 1,596 subjects were included. For the primary outcomes, no exercise modality showed an overall statistically significant advantage over the control group in improving depressive symptoms. For the secondary outcome, cognitive exercise significantly improved the MMSE scores compared with daily activities (MD = 3.50, 95% CI [2.29, 4.71]). For UPDRS III, no significant overall difference was observed between exercise interventions and the control group.

CONCLUSION: The available evidence does not provide stable or modestly consistent support for a clear overall benefit of different exercise interventions on depressive symptoms in patients with Alzheimer's disease, cognitive impairment, and Parkinson's disease. Cognitive exercise may help improve cognitive function, whereas the potential benefits of multicomponent exercise for motor function in Parkinson's disease should be interpreted with caution. In the future, large randomized controlled trials with clearer stratification, specific protocols, and standardized exercise prescriptions are needed to further define the optimal populations and intervention effects of different exercise modalities.

https://www.crd.york.ac.uk/prospero/, identifier CRD420261280926.},
}

@article {pmid42266272,
year = {2026},
author = {Fu, H and Yang, J and Zhang, M},
title = {Treg-microglia crosstalk in Alzheimer's disease: stage-dependent dynamics, molecular mechanisms, and translational challenge.},
journal = {Frontiers in aging neuroscience},
volume = {18},
number = {},
pages = {1838306},
pmid = {42266272},
issn = {1663-4365},
abstract = {Alzheimer's disease (AD) is characterized by amyloid-beta (Aβ) deposition, tau hyperphosphorylation, and chronic neuroinflammation. Emerging evidence from preclinical models suggests that aberrant immune crosstalk between regulatory T cells (Tregs) and microglia may contribute to disease progression, though its precise role in human AD remains to be fully elucidated. In rodent models, Tregs have been shown to cross the blood-brain barrier and, through cell-contact-dependent mechanisms and secretion of pro-resolutive factors such as transforming growth factor-β, appear to promote microglial transitions toward pro-resolutive states and facilitate Aβ phagocytosis. However, these mechanisms have been predominantly demonstrated in transgenic mouse strains with early-onset amyloid pathology, and their relevance to the slow, aging-associated progression of human sporadic AD requires cautious interpretation. In AD animal models, reductions in Treg numbers and suppressive function coincide with microglial dysregulation, with the interaction between these cell types shifting from homeostatic to pro-inflammatory states as pathology advances. It is critical to note that while such findings suggest a potential regulatory axis, they derive largely from simplified animal systems that do not fully recapitulate human immune aging, genetic heterogeneity, or decades-long disease kinetics. Moreover, therapeutic strategies targeting this crosstalk that show efficacy in mice have yielded inconsistent results in early human trials, highlighting significant translational gaps. This review critically assesses the current preclinical evidence, emphasizing that findings from rodent models should be interpreted as hypothesis-generating rather than definitive proof of mechanism in human disease. We underscore the urgent need for validation through human tissue analysis, cerebrospinal fluid biomarkers, and advanced humanized model systems before Treg-microglia interactions can be established as robust therapeutic targets for AD.},
}

@article {pmid42266273,
year = {2026},
author = {Li, Y and Mallika, AP and Baghel, MS and Shravage, BV and Shang, P},
title = {Editorial: Mitochondrial dysfunction in cellular and molecular mechanisms of brain aging.},
journal = {Frontiers in aging neuroscience},
volume = {18},
number = {},
pages = {1866752},
pmid = {42266273},
issn = {1663-4365},
}

@article {pmid42266363,
year = {2026},
author = {Li, X and Zhao, X and Huang, Y and Tang, J},
title = {Peripheral Nerve Conduction in Alzheimer's vs. Late-Life Depression: A Comparative Study.},
journal = {Neuropsychiatric disease and treatment},
volume = {22},
number = {},
pages = {611214},
pmid = {42266363},
issn = {1176-6328},
abstract = {BACKGROUND: Alzheimer's disease (AD) and late-life depression (LLD) patients both exhibit peripheral motor nerve conduction impairments, but with distinct patterns, highlighting divergent neurophysiological mechanisms in these aging-related disorders.

OBJECTIVE: To compare peripheral nerve conduction function among normal cognition (NC), older adults with AD, and LLD.

METHODS: All the participants were enrolled and assigned to AD, LLD and aged-matched NC controls (all ≥60 years, n=60, respectively). Sensory conduction of the median and sural nerves, and motor conduction of the median and common peroneal nerves, were assessed. Key parameters included latency, amplitude, and conduction velocity. Group differences were analyzed after adjusting for gender, age, education, height, and comorbid medical conditions.

RESULTS: By controlling gender, age, height, education level, and somatic diseases with inter-group differences, compared with NC group, the median nerve motor conduction in AD group showed prolonged proximal latency (3.21 vs. 3.65 ms, P=0.023), reduced amplitude (proximal: 7.30±2.02 vs. 3.89±0.57 mV; distal: 6.13±2.17 vs. 4.12±2.38 mV, both P<0.001), and slowed conduction velocity (56.46±5.18 vs. 49.29±6.27 m/s, P=0.002). LLD group exhibited more pronounced latency prolongation (proximal: 3.21 vs. 4.06 ms; distal: 7.18 vs. 7.98 ms, both P<0.001) and greater amplitude reduction (proximal: 7.30±2.02 vs. 3.65±0.66 mV; distal: 6.13±2.17 vs. 3.18±1.88 mV, both P<0.001). In terms of the common peroneal nerve motor conduction, function AD group had significantly slower conduction velocity (48.88±5.82 vs. 42.85±5.27 m/s, P=0.033). LLD group showed prolonged proximal latency (4.25 vs. 5.77 ms, P<0.001). No significant differences were found in sensory conduction parameters across groups after adjustment.

CONCLUSION: Both AD and LLD groups were associated with peripheral motor neuropathy, but the pattern of impairment differs. AD is marked by generalized conduction slowing, while LLD shows more severe latency delays and amplitude loss, suggesting distinct pathophysiological pathways. These findings provide new insights into the peripheral nervous system's involvement in age-related neurocognitive and mood disorders.},
}

@article {pmid42266426,
year = {2026},
author = {Schroder, A and Moggridge, J and Salhab, HA and Micallef, C and Wu, J and Bristow, M and Pérez-García, F and Alvarez-Valle, J and Vos, SB and Yousry, TA and Thornton, JS and Barkhof, F and Duncan, JS and Alexander, DC and Grech-Sollars, M},
title = {InnerEye-HS: a disease-agnostic clinical tool for hippocampal segmentation.},
journal = {Brain communications},
volume = {8},
number = {3},
pages = {fcag183},
pmid = {42266426},
issn = {2632-1297},
abstract = {The hippocampus is subject to atrophy in both Alzheimer's disease and temporal lobe epilepsy. Hippocampal volumes thus provide an early biomarker for these diseases. However, automated segmentation models typically lack robustness to disease-related changes in the hippocampus. In this work, we present the InnerEye hippocampal segmentation tool (InnerEye-HS). This deep learning tool was trained on MRI scans across the Alzheimer's disease spectrum, providing exposure to varying hippocampal size and topology. We validate the model against manually segmented hippocampi on both clinical dementia and epilepsy datasets collected in clinical settings and compare our model's performance to four other freely available tools (Automatic Segmentation of Hippocampal Subfields (ASHS), FreeSurfer, FastSurfer and HIPPOSEG). When compared to other freely available tools, the InnerEye-HS model provides the best Dice scores in our hospital dementia dataset (mean = 0.85 ± 0.02, P ≤ 0.0125), and InnerEye-HS and ASHS provided the best Dice scores in our epilepsy dataset (InnerEye-HS mean = 0.85 ± 0.02, ASHS mean = 0.84 ± 0.03). Furthermore, we found a high correlation (R[2] = 0.85) between hippocampal volumes extracted from ground-truth segmentations and those extracted from InnerEye-HS segmentations, demonstrating the model's ability to robustly segment the hippocampus throughout the disease time course. In summary, we present the InnerEye-HS model and demonstrate its advantage over currently available tools. These advantages highlight the clinical utility of our tool.},
}

@article {pmid42266427,
year = {2026},
author = {Mikhailenko, E and Savola, S and Kero, M and Tienari, PJ and Myllykangas, L and Kaivola, K},
title = {Genetic analysis of limbic-predominant age-related TDP-43 encephalopathy neuropathologic change in a population-based cohort of the oldest old.},
journal = {Brain communications},
volume = {8},
number = {3},
pages = {fcag189},
pmid = {42266427},
issn = {2632-1297},
abstract = {Limbic-predominant age-related TDP-43 encephalopathy neuropathologic change is a common proteinopathy in the oldest old that is associated with cognitive decline. Although the genetic basis of limbic-predominant age-related TDP-43 encephalopathy neuropathologic change remains largely unknown, TMEM106B, GRN and APOE loci are frequently implicated. Here, we examined nine previously reported limbic-predominant age-related TDP-43 encephalopathy neuropathologic change risk loci (ARHGEF28, APOE, GRN, KAZN, LHX1, TPCN1, TMEM106B, UNC13C and WWOX) in a population cohort of 262 individuals from the Vantaa 85 + study. We also tested whether Alzheimer's disease polygenic risk score without APOE was associated with limbic-predominant age-related TDP-43 encephalopathy neuropathologic change. Using ordinal logistic regression models, GRN rs5848 (odds ratio = 2.45, 95% confidence interval: 1.71-3.52, adjusted P = 5.75 × 10[-6]), APOE ε4 dose (odds ratio = 1.73, 95% confidence interval: 1.07-2.80, adjusted P = 0.030) and KAZN rs72643142 (odds ratio = 2.38, 95% confidence interval: 1.38-4.11, adjusted P = 0.0048) were associated with higher limbic-predominant age-related TDP-43 encephalopathy neuropathologic change stage. Additionally, Alzheimer's disease polygenic risk score without APOE was associated with limbic-predominant age-related TDP-43 encephalopathy neuropathologic change after adjusting for age, sex, Alzheimer's disease pathology and APOE ε4 dose (odds ratio = 1.36, 95% confidence interval: 1.06-1.75, adjusted P = 0.027). Our findings contribute to the understanding of limbic-predominant age-related TDP-43 encephalopathy neuropathologic change genetics and suggest shared biological processes between limbic-predominant age-related TDP-43 encephalopathy neuropathologic change and Alzheimer's disease.},
}

@article {pmid42266508,
year = {2026},
author = {Khajuria, P and Kour, D and Sharma, K and Singh, L and Banoo, R and Manhas, D and Ramajayan, P and Nandi, U and B Bharate, S and Ahmed, Z and Kumar, A},
title = {AMPK-mediated autophagy induction by bisdemethoxycurcumin attenuates senescence and amyloid pathology in 3xTg-AD mice.},
journal = {Autophagy reports},
volume = {5},
number = {1},
pages = {2675164},
pmid = {42266508},
issn = {2769-4127},
abstract = {Alzheimer disease (AD) pathology is accompanied by increased senescence and reduced levels of autophagy in the brain. We investigated whether pharmacologically inducing autophagy could alter the senescent phenotype and ameliorate AD pathology. We discovered that Bisdemethoxycurcumin (BDMC), a natural compound found in Curcuma longa, stimulates autophagy in primary astrocytes. We found that autophagy and senescence exhibit an inverse relationship in aging astrocytes, with increased expression of senescent proteins and downregulation of autophagic proteins. However, treatment of aged astrocytes with BDMC reversed the senescent phenotype by ameliorating the impaired autophagy. Interestingly, the senescent phenotype persisted when autophagy was downregulated by knockdown of AMPK. Additionally, BDMC-induced autophagy aided in the removal of amyloid beta (Aβ) that was administered externally to the astrocytes. Further, to validate these results in a mouse model of AD, we confirmed that BDMC significantly penetrates the blood-brain barrier (BBB) in mice. Therefore, we administered 50 and 100 mg/kg b.w. of BDMC to transgenic 3xTg-AD mice for two months. In their hippocampus, the Control 3xTg-AD animals showed more senescent cells and lower autophagy levels. In contrast, autophagic proteins were significantly upregulated while senescence indicators, such as senescence-associated secretory phenotype (SASP) proteins, were sharply downregulated in the brain of treated animals. We discovered that the hippocampus of treated mice had a significantly lower Aβ load. These molecular changes in the brain were ultimately reflected in the improved working memory and neuromuscular coordination behavior of mice treated with BDMC. This study warrants further evaluation of BDMC for the management of AD.},
}

@article {pmid42266582,
year = {2026},
author = {Yang, YY and Zeng, XX and He, X and Huang, XL and Xu, MX and Mao, FL and Wang, YQ and Qin, FL},
title = {Predictive value of Galectin-3 in cognitive impairment: a systematic review and meta-analysis.},
journal = {Frontiers in neurology},
volume = {17},
number = {},
pages = {1851363},
pmid = {42266582},
issn = {1664-2295},
abstract = {BACKGROUND: Cognitive Impairment (CI) is an increasingly serious public health problem in an aging society. Its rising incidence rate is closely linked to functional decline and increased mortality risk. Because of its insidious onset and irreversible progression, early identification is particularly crucial. Neuroinflammation and vascular injury play important roles in the occurrence and development of CI. Galectin-3 (Gal-3), as a biomarker involved in the inflammatory response and vascular lesion process, may have potential value in the early prediction and risk assessment of CI.

METHODS: This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. Seven databases were systematically retrieved from their establishment until March 8, 2026. Two independent researchers conducted literature screening, data extraction, and quality evaluation using the Newcastle-Ottawa Scale. The combined effect size was calculated using the weighted mean difference (WMD) or standardized mean difference (SMD), with a 95% confidence intervals (CIs). Heterogeneity was evaluated using the chi-square (χ [2]) test (Cochran's Q) and the inconsistencies index test (I [2]), and publication bias was assessed using funnel plots and Egger's regression tests.

RESULTS: This systematic review included nine studies comprising 877 patients with cognitive impairment (CI) and 715 healthy controls. The meta-analysis demonstrated that peripheral Gal-3 levels were significantly higher in the CI group compared with controls (WMD: 0.85; 95%CI: 0.42-1.28; p < 0.0001), despite substantial heterogeneity across studies (I [2] = 98%). Subgroup analyses further revealed that Gal-3 levels were significantly elevated in CI with vascular risk factors (WMD: 1.76; 95%CI: 0.10-3.43; p = 0.04), whereas no statistically significant difference was observed in CI without vascular risk factors (p = 0.06). Regarding specific disease types, Gal-3 levels were significantly higher in patients with mild cognitive impairment (MCI) (WMD: 0.72; 95%CI: 0.04-1.40; p = 0.04), but not in those with Alzheimer's disease (AD) (p = 0.11).

CONCLUSION: Elevated Gal-3 levels are significantly associated with cognitive impairment and may serve as a convenient and effective biomarker for its early detection, particularly in CI with vascular risk factors and MCI. However, the evidence remains insufficient for AD, warranting further large-scale studies.

https://www.crd.york.ac.uk/PROSPERO/view/CRD420261293666, identifier CRD420261293666.},
}

@article {pmid42266620,
year = {2026},
author = {Sudasinghe, KH and Hall, SE},
title = {Intermittent fasting and neuroprotection in Alzheimer's disease: metabolic mechanisms, cellular signaling, and brain-peripheral crosstalk.},
journal = {Frontiers in nutrition},
volume = {13},
number = {},
pages = {1839995},
pmid = {42266620},
issn = {2296-861X},
abstract = {Intermittent fasting (IF) promotes a metabolic switch characterized by reduced glucose and insulin availability along with increased lipolysis and ketone body production, particularly β-hydroxybutyrate (βOHB). In the brain, IF enhances metabolic flexibility by facilitating ketone utilization and supporting the astrocyte-neuron lactate shuttle (ANLS), partially compensating for cerebral glucose hypometabolism which is commonly observed in Alzheimer's disease (AD). Beyond bioenergetics, IF activates autophagy and inhibits mTOR signaling, promoting protein clearance and cellular homeostasis. Neuroinflammation is also attenuated with IF through the modulation of microglial activation. IF further induces increased levels of brain-derived neurotrophic factor (BDNF), thereby supporting synaptic plasticity and neuronal resilience. At the systemic level, IF enhances brain-peripheral crosstalk by improving adipose tissue function (e.g., leptin sensitivity and adipokine balance) and stimulating skeletal muscle-derived myokine signaling, which collectively influence brain metabolism and inflammation. These integrated mechanisms converge to reduce amyloid-β accumulation, tau pathology, and neuroinflammation, ultimately improving synaptic function and cognitive outcomes, as evidenced by preclinical rodent models and emerging clinical studies.},
}

@article {pmid42266879,
year = {2026},
author = {Amuthan, S and Senthilkumar, NC},
title = {Ensemble Deep Learning Denoising (EDLD) model and optimized OTSU segmentation for Alzheimer's disease diagnosis using MRI images.},
journal = {Frontiers in artificial intelligence},
volume = {9},
number = {},
pages = {1743818},
pmid = {42266879},
issn = {2624-8212},
abstract = {Diagnosing Alzheimer's disease (AD) is necessary to determine treatment options. AD categorization using machine learning (ML) relies on difficult, manually specified features. The most important stage in AD diagnosis is denoising to restore image stability and quality. An ensemble image denoising technique that combines Attention Guided Convolutional Neural Network (AGCNN), Adaptive Denoising Autoencoder (ADAE), and Gaussian Deep Belief Network (GDBN) improves image denoising performance. The hybrid AGCNN reduces noise and aligns along the global route by combining global and local characteristics. In ADAE, the encoder learns picture representations using convolutional layers (CLs) while the decoder uses deconvolutional layers. In addition, the GDBN extends the standard Deep Belief Network (DBN) to Gaussian Restricted Boltzmann Machines (RBMs). Ensemble learning selects the approach with the greatest Peak Signal-to-Noise Ratio (PSNR) to integrate learning outcomes. After separating the background from the foreground by calculating the variances within the two groups, OTSU determines the threshold that minimizes the weighted sum of the variances. Levy Grasshopper Optimization Algorithm (LGOA) optimizes threshold selection by mimicking grasshopper swarming. VGG16, the DCNN model, is pre-trained for Alzheimer's datasets. The results are Sensitivity (SEN -95.86%), specificity (SPC - 94.93%), precision (PPV - 94.55%), F1-score (F1 - 95.21%), accuracy (ACC -95.87%), and Area Under the Receiver Operating Characteristic Curve (AUC - 96.45%) assess system and method performance.},
}

@article {pmid42267079,
year = {2026},
author = {Leach, HJ and Stephens, JA and Ehlers, DK},
title = {Synergistic effects of group-based exercise to reduce loneliness and social isolation and to prevent cognitive decline among older adults with cancer.},
journal = {Frontiers in aging},
volume = {7},
number = {},
pages = {1835531},
pmid = {42267079},
issn = {2673-6217},
abstract = {The growing population of older cancer survivors faces an elevated risk of accelerated cognitive decline due to the combined effects of aging and cancer-related cognitive impairment. Loneliness and social isolation have also been linked to poorer cognitive outcomes and increased risk of Alzheimer's Disease and Related Dementias (ADRD). At the same time, regular physical activity and social support interventions may improve cognitive function and reduce risk of cognitive decline. Despite these parallel lines of evidence, few interventions have addressed these modifiable risk factors simultaneously, particularly among older cancer survivors. In this perspective, we propose that group-based exercise may provide synergistic benefits for cognitive health by addressing both physical activity and social engagement. We present a conceptual model in which participation in group exercise promotes exercise-induced neurobiological adaptations that support cognitive function while simultaneously enhancing social connectedness. These processes may reduce loneliness and social isolation, promoting cognitive engagement. We also highlight key considerations for future research, including the potential for virtual or remotely delivered group exercise to increase accessibility, the importance of group dynamics in fostering social support, and the need to incorporate validated measures of loneliness, social isolation, and cognitive function in intervention studies.},
}

@article {pmid42267139,
year = {2026},
author = {Salihoglu, R and Can, Ş and Dandekar, T and Bencurova, E},
title = {Integrated Multi-Tissue Transcriptomics Reveals Antagonistic Pleiotropy in Aging and Alzheimer's Disease.},
journal = {Computational and structural biotechnology journal},
volume = {35},
number = {1},
pages = {0134},
pmid = {42267139},
issn = {2001-0370},
abstract = {Aging is the strongest risk factor for Alzheimer's disease (AD); however, some individuals age without major cognitive decline, suggesting that resilience and vulnerability may be associated with distinct molecular trajectories. To investigate these trajectories, we performed an integrated transcriptomic analysis of human dermal fibroblasts (GSE113957) and multi-region brain profiles (GSE48350), extending previous dataset-specific studies that focused primarily on age prediction, regional variation, or synaptic/immune signatures. Healthy aging and AD were compared within a novel antagonistic pleiotropy (AP) framework. This approach prioritized genes and candidate transcriptional regulators with opposing age and disease-associated expression patterns. Across tissues, healthy aging was associated with relative preservation of metabolic, mitochondrial, and lipid-homeostatic programs, whereas AD was associated with suppression of these programs alongside greater inflammatory and immune pathway activity. AP-Vulnerability genes (Age↓/AD↑), including TAC1, FREM3, and SLC25A46, declined with age but were induced in AD. Conversely, AP-Resilience genes (Age↑/AD↓), including PTH2, PPDPF, and NEFH, increased during healthy aging but were reduced in AD. Pathway analyses suggested an association between metabolic programs and resilience, and between immune activation and vulnerability. Transcription-factor inference prioritized PPARG, NFE2L2, and TEAD4 as candidate resilience-associated regulators, showing directionally opposite patterns relative to immune- and developmental-related regulators in AD.},
}

@article {pmid42267153,
year = {2026},
author = {Wessinger, CM and Park, KS and DuBois, SL and Wideman, L and Armstrong, BD and Vance, JC and Kibildis, SW and Som-Pimpong, H and Etnier, JL},
title = {APOE-ε4 moderates the association between diet quality and executive function in middle-aged women at increased risk for Alzheimer's disease.},
journal = {Journal of nutritional science},
volume = {15},
number = {},
pages = {e41},
pmid = {42267153},
issn = {2048-6790},
abstract = {We examined whether diet quality is associated with executive function (EF) in middle-aged women with a family history of Alzheimer's disease (AD) and whether this is moderated by a genetic AD risk factor, APOE-ε4 allele carriage. Data from 102 low-physically active women (AgeMean = 56.9 ± 5.8 years) were analyzed cross-sectionally. Diet quality was quantified via the Healthy Eating Index-2020 (HEI-2020). Overall EF and sub-domains (working memory [WM], exogenous inhibitory control [ICex], endogenous inhibitory control [ICen], and cognitive flexibility) were measured using neurocognitive assessments. APOE-ε4 carriage was determined from saliva. Moderated regression models tested HEI-2020*APOE-ε4 interactions; significant (p < .05) and near-significant (p < .10) interactions were followed by simple slope analyses. Main effects of HEI-2020 predicted overall EF (p = .033) and WM (p = .003). Interaction effects of HEI-2020*APOE-ε4 for EF and WM (p's = .056-.038) were such that diet quality was positively associated with overall EF (p = .003) and WM (p = .005) in noncarriers only. Main effects of select HEI-2020 sub-scores were observed for overall EF and sub-domains (p's = .001-.047). Interaction effects of total vegetables*APOE-ε4 on overall EF and ICex, saturated fatty acids*APOE-ε4 on overall EF and WM, and added sugars*APOE-ε4 on ICen (p's = .007-.074) were such that sub-scores were positively associated with cognition in noncarriers only (p's < .05). Diet quality and select sub-scores were positively associated with EF in middle-aged women without APOE-ε4 only. Future work should explore if APOE-ε4 carriers require a threshold of diet quality to yield cognitive benefits.},
}

@article {pmid42267321,
year = {2026},
author = {Akinwumi, PO and Qian, M and Olorunsogbon, TA and Zhou, C and Huang, S},
title = {Machine learning for Alzheimer's disease progression under extreme class imbalance.},
journal = {Frontiers in neuroscience},
volume = {20},
number = {},
pages = {1736992},
pmid = {42267321},
issn = {1662-4548},
abstract = {BACKGROUND: Timely identification of individuals at risk for Alzheimer's disease (AD) progression remains a major clinical challenge. Traditional cognitive assessments provide limited prognostic insight, while many machine learning (ML) models rely on costly biomarkers or poorly interpretable algorithms that limit clinical scalability. This study evaluated whether widely available baseline demographic, clinical, and cognitive measures could support short-term progression prediction using interpretable ML methods under extreme class imbalance.

METHODS: We analyzed 3,240 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI), of whom 2,423 had valid 24-month follow-up data. The primary outcome was strict unidirectional diagnostic worsening within 24 months (13 events; 0.5%). Baseline demographic, clinical, and cognitive variables were used to train XGBoost and logistic regression models under natural class imbalance using stratified k-fold cross-validation with out-of-fold predictions. Model performance was evaluated using AUROC, area under the precision-recall curve (AUPRC), calibration analyses, and bootstrap confidence intervals. Sensitivity analyses evaluated cost-sensitive learning, threshold optimization, and alternative imputation strategies (KNN and MICE). Longitudinal mixed-effects modeling was conducted separately to characterize cognitive decline and was not used as input to the predictive models. SHAP (Shapley Additive Explanations) quantified feature contributions.

RESULTS: Under natural class imbalance, XGBoost achieved AUROC = 0.912 and AUPRC = 0.051, while logistic regression achieved AUROC = 0.787 and AUPRC = 0.038. Although discrimination exceeded baseline prevalence, precision remained low and threshold optimization produced substantial false-positive burdens, limiting immediate clinical applicability. Cost-sensitive learning did not materially improve performance. MICE imputation produced results comparable to median imputation, whereas KNN imputation reduced performance. SHAP analyses identified baseline cognitive severity, functional measures, and diagnostic status as dominant predictors. Mixed-effects modeling confirmed significant cognitive decline over time (β = -0.027 points/month, p < 0.001).

CONCLUSION: Accessible baseline clinical and cognitive variables contain measurable but limited predictive signal for short-term AD progression under extreme event scarcity. These findings should be interpreted as an early-stage proof-of-concept rather than a clinically deployable decision-support tool. External validation remains necessary before clinical translation.},
}

@article {pmid42267529,
year = {2026},
author = {Lohnes, BJ and Myskova, A and Tyagi, A and Hartwig, UF and Poddar, NK},
title = {Rewiring mTOR signaling in Alzheimer's disease: emerging mTOR modulators beyond oncology.},
journal = {Bioscience reports},
volume = {46},
number = {6},
pages = {},
doi = {10.1042/BSR20260203},
pmid = {42267529},
issn = {1573-4935},
abstract = {While Alzheimer's disease (AD) is the most common cause of dementia, curative treatments remain unavailable. Despite distinct pathologies between AD and cancer, shared dysregulation of the PI3K-AKT-mTOR signaling pathway promotes both disease states. mTOR activity significantly contributes to AD hallmarks, including amyloid-beta production, tau hyperphosphorylation, and altered metabolism and autophagy through mTOR-mediated signaling and downstream targets such as BACE-1, GSK-3β, and AChE. Consequently, mTOR-modulating compounds, demonstrating promising results in oncology, present a viable strategy to potentially halt or reverse AD progression. This review discusses the potential application of 37 mTOR pathway-modulating compounds, many originally developed for cancer treatment, given their shared molecular targets. We systematically classified the compounds based on their origin as marine, plant-derived, structural analogs, and synthetic compounds. This framework reveals a fundamental trade-off, as the structural novelty and pleiotropic effects of natural products are often counterbalanced by poor pharmacokinetics, whereas the pharmacological precision of synthetic compounds is frequently limited by compensatory feedback loops. Furthermore, we analyze translational challenges, including balancing efficacy with toxicity, limitations in blood-brain barrier penetration, and the need for patient stratification using robust biomarkers. We conclude that the most promising therapeutic approach for AD involves synergistically combining natural products with rational synthetic design. Leveraging natural products as a source of novel chemical scaffolds and employing targeted synthetic engineering to overcome their pharmacokinetic limitations, this strategy moves beyond blunt pathway inhibition. Ultimately, this enables a highly nuanced modulation of the mTOR network, providing the basis for future preclinical and clinical drug development in AD.},
}

@article {pmid42267564,
year = {2026},
author = {Yan, GJ and Wang, XY and Shi, XY and Lu, MN and Wang, D and Ye, CJ and Li, SS and Yang, CD and Liang, XW and Zhang, YJ and Yang, XW and Hu, T and Xiyang, YB},
title = {miR-449a modulates Alzheimer's disease pathology through regulation of Navβ2.},
journal = {Zoological research},
volume = {47},
number = {3},
pages = {781-800},
doi = {10.24272/j.issn.2095-8137.2025.430},
pmid = {42267564},
issn = {2095-8137},
abstract = {Progression of Alzheimer's disease (AD) from mild cognitive impairment (MCI) to dementia occurs gradually and remains mechanistically unresolved, limiting development of effective interventions. This study investigated the contribution of Navβ2 and its upstream regulatory microRNA, miR-449a, to MCI- and AD-associated neuropathology in multiple mouse models. Results revealed that Navβ2 expression was dysregulated in MCI and AD mice, accompanied by synaptic abnormalities, aberrant amyloid precursor protein (APP) processing, and disrupted Nav1.1α expression. Importantly, manipulation of miR-449a markedly influenced synaptic function and cognition through regulation of Navβ2, with miR-449a overexpression alleviating and miR-449a inhibition exacerbating cognitive impairment. Co-transfection assays further demonstrated that the effects of miR-449a on APP metabolism were mediated by Navβ2. Electrophysiological analyses provided additional evidence that the miR-449a/Navβ2 axis participates in regulation of cognitive function. Together, these findings provide new mechanistic insight into synaptic dysfunction and cognitive decline in AD and identify the miR-449a/Navβ2 axis as a candidate therapeutic target for cognitive impairment. Further investigation of the miR-449a/Navβ2 axis may facilitate development of targeted strategies to preserve synaptic integrity and cognitive function during AD progression.},
}

@article {pmid42267641,
year = {2026},
author = {Shanks, HRC and Chen, S and Onuska, KM and Schmitz, TW},
title = {A lifespan staging model of basal forebrain cholinergic vulnerability.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {6},
pages = {e71380},
doi = {10.1002/alz.71380},
pmid = {42267641},
issn = {1552-5279},
support = {176677//Alzheimer's Society of Canada/ ; 22-11//Alzheimer's Society of Canada/ ; 453677/CAPMC/CIHR/Canada ; 193293/CAPMC/CIHR/Canada ; },
abstract = {The cholinergic neurons of the basal forebrain are among the most vulnerable cell types to age- and Alzheimer's disease-related dysfunction and neurodegeneration. However, the biological bases of basal forebrain cholinergic vulnerability (the why) and the temporal sequence (the how) have yet to be fully resolved. In this review, we summarize multi-disciplinary evidence to present a lifespan staging model of basal forebrain cholinergic vulnerability, which outlines how converging biological stressors position these neurons to fail. We trace the origins of basal forebrain cholinergic vulnerability from evolutionary and neurodevelopmental pressures, which ultimately interact with midlife stressors to culminate in two divergent trajectories of cholinergic aging: resilient and vulnerable. Lastly, we highlight that the branch point in cholinergic aging trajectories may serve as a critical window for intervention if sensitive, specific, and clinically scalable in vivo cholinergic biomarkers can be developed.},
}

@article {pmid42258677,
year = {2026},
author = {Yin, M and Ravindran, KKG and Hadjipanayi, C and Bannon, A and Monica, CD and Rapeaux, A and Lande, TS and Dijk, DJ and Constandinou, T},
title = {Using Legacy Polysomnography Data to Train a Radar System to Quantify Sleep in Older Adults and People living with Dementia.},
journal = {IEEE transactions on bio-medical engineering},
volume = {PP},
number = {},
pages = {},
doi = {10.1109/TBME.2026.3701134},
pmid = {42258677},
issn = {1558-2531},
abstract = {OBJECTIVE: Ultra-wideband (UWB) radar technology offers a promising solution for unobtrusive and cost-effective in-home sleep monitoring. However, the limited availability of radar sleep data poses challenges in building robust models that generalize across diverse cohorts and environments. This study proposes a novel deep transfer learning framework to enhance sleep stage classification using radar data.

METHODS: An end-to-end neural network was developed to classify sleep stages based on nocturnal respiratory and motion signals. The network was trained using a combination of large-scale polysomnography (PSG) datasets and radar data. A domain adaptation approach employing adversarial learning was utilized to bridge the knowledge gap between PSG and radar signals. Validation was performed on a radar dataset of 47 older adults (mean age: 71.2 ± 6.5), including 18 participants with prodromal or mild Alzheimer's disease.

RESULTS: The proposed network structure achieves an accuracy of 79.5% with a Kappa value of 0.65 when classifying wakefulness, rapid eye movement, light sleep and deep sleep. Experimental results confirm that our deep transfer learning approach significantly enhances automatic sleep staging performance in the target domain.

CONCLUSION: This method effectively addresses challenges associated with data variability and limited sample size, substantially improving the reliability of automatic sleep staging models, especially in contexts where radar data is limited.

SIGNIFICANCE: The findings underscore the viability of UWB radar as a nonintrusive, forward-looking sleep assessment tool that could significantly benefit care for older people and people with neurodegenerative disorders.},
}

@article {pmid42259020,
year = {2026},
author = {López-Martos, D and Cacciaglia, R and Suárez-Calvet, M and Salvadó, G and Shekari, M and González-Escalante, A and Milà-Alomà, M and Brugulat-Serrat, A and Minguillon, C and Tonietto, M and Borroni, E and Klein, G and Quijano-Rubio, C and Kollmorgen, G and Zetterberg, H and Blennow, K and Gispert, JD and Grau-Rivera, O and Sánchez-Benavides, G and , },
title = {Multimodal biomarker characterization of amnestic objective subtle cognitive decline in aging and preclinical Alzheimer's disease.},
journal = {The journal of prevention of Alzheimer's disease},
volume = {13},
number = {7},
pages = {100612},
doi = {10.1016/j.tjpad.2026.100612},
pmid = {42259020},
issn = {2426-0266},
abstract = {BACKGROUND: The objective of this study was to provide a multimodal biomarker characterization of amnestic objective subtle cognitive decline (obj-SCD) in aging and preclinical Alzheimer's disease (AD).

METHODS: Prospective observational study; data from the Alzheimer's and Families+ (ALFAs+) cohort, including cognitively unimpaired (CU) individuals with available baseline CSF biomarkers (normal or AD continuum profiles) and longitudinal neuropsychological assessment (2 time points, 3-year follow-up). Amnestic obj-SCD was defined using robust longitudinal neuropsychological references with multivariate base rate thresholds of significant decline (Free and Cued Selective Reminding Test, Memory Binding Test, Wechsler Memory Scale IV: Logical Memory). Study outcomes included plasma p-tau217, NfL, and GFAP; CSF p-tau181/Aβ42, NfL, and GFAP; Aβ and tau PET; and MRI Grey Matter volume (GMv). The associations of amnestic obj-SCD with fluid (plasma and CSF) and neuroimaging biomarkers (PET and GMv) were evaluated using mixed-effects and voxel-wise linear regression models, respectively.

RESULTS: 350 CU individuals were included (mean age 61 years; 60% female; mean education 14 years; 35% CSF Aβ-positive). Amnestic obj-SCD was identified in 10% of the sample, associated with greater AD pathology (higher plasma p-tau217, CSF p-tau181/Aβ42, global Aβ PET, medial temporal tau PET), neurodegeneration (higher plasma and CSF NfL, reduced GMv in cingulate cortex, longitudinal GMv reductions in hippocampus) and inflammation (higher plasma and CSF GFAP, longitudinal GMv increases in neocortical brain regions).

DISCUSSION: These findings highlight the need for standardized clinical staging criteria to enhance early detection and risk stratification in aging and preclinical AD.},
}

@article {pmid42259049,
year = {2026},
author = {Wang, C and Song, X and Chen, D and Su, J and Wang, Y and Huang, C and Wei, W},
title = {Gold-nanocube-based SERS sensor for accurate detection of Alzheimer's disease biomarkers: Aβ42 and MAO-B.},
journal = {Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy},
volume = {362},
number = {},
pages = {128185},
doi = {10.1016/j.saa.2026.128185},
pmid = {42259049},
issn = {1873-3557},
abstract = {Considering the irreversible nature of Alzheimer's disease (AD), early diagnosis is of great importance for AD treatment. Both β-amyloid (Aβ) and monoamine oxidase B (MAO-B) are potential biomarkers for AD. This study developed a surface-enhanced Raman scattering (SERS) sensor using gold-nanocube (OX-AuNCs) to detect Aβ42 and MAO-B. OX-AuNCs, a type of gold-nanocube with open gaps, achieved a Raman enhancement factor of 8.99 × 10[8] due to numerous hot spots. The specific affinity between Thioflavin T (ThT) and Aβ42 inhibits ThT's intramolecular rotation, reducing its SERS signal. This reduced signal showed a linear correlation with Aβ42 concentrations from 66.70 pM to 0.20 μM, achieving a limit of detection (LOD) at 44.30 pM, while also distinguishing different aggregation levels of Aβ42. Interestingly, SERS intensity of phenethylamine (PEA) also decreased significantly when interacting with MAO-B. A linear relationship was found between the change in PEA intensity and MAO-B concentration (0.01-20.00 μg mL[-1]), yielding an LOD of 5.00 ng mL[-1]. The proposed SERS sensor effectively detected two potential AD biomarkers, Aβ42 and MAO-B, in artificial cerebrospinal fluid (ACSF) and human serum with satisfactory recovery rates, respectively. These results show promise for clinical diagnosis and drug screening for AD.},
}

@article {pmid42259141,
year = {2026},
author = {Alnsour, L and Al-Samydai, A and Sadek, B and Akour, A},
title = {Repurposing antidiabetics for Alzheimer's disease and related neurodegenerative disorders: Translational challenges and role of nanoparticle-mediated CNS targeting.},
journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie},
volume = {200},
number = {},
pages = {119614},
doi = {10.1016/j.biopha.2026.119614},
pmid = {42259141},
issn = {1950-6007},
abstract = {Diabetes mellitus has been linked to cognitive impairment and Alzheimer's disease (AD). They share common pathologic pathways, including insulin resistance, mitochondrial dysfunction, oxidative stress, and chronic neuroinflammation. These shared mechanisms have prompted interest in repurposing antidiabetic agents as promising therapies for neurodegenerative diseases. Despite this overlap, these drugs face translational challenges, primarily due to their poor penetration across the blood-brain barrier (BBB) and, consequently, poor central nervous system (CNS) bioavailability. Nanoparticle-based drug delivery offers an alternative route to improve targeting of the CNS by increasing the drug stability and augmenting transport across the BBB. Although preclinical evidence showed promising results, the extent to which these findings translate into clinically tangible outcomes remains uncertain. This review critically evaluates the main preclinical studies on nanoparticle-mediated delivery of antidiabetic agents, with particular emphasis on AD and diabetes-associated cognitive impairment, where most available data are concentrated. We also discuss the main brain-targeting strategies, their limitations, and the translational challenges to their clinical application, particularly for conditions beyond AD, where the evidence remains sparse. Addressing these barriers is crucial for the development of nanomedicine-based approaches from bench to bedside. This review provides a critical standpoint on the field and highlights priorities for future research aimed at the effective translation of nanoparticle-enabled therapies for neurodegenerative diseases.},
}

@article {pmid42259196,
year = {2026},
author = {Yao, W and Qu, M and Deng, C and Zhang, C and Zhang, X and Hu, X and Zhang, J and Yang, T and Liu, F and Wang, T and Li, D and Wang, X},
title = {Bacteria-derived equol alleviates Aβ toxicity in C. elegans through PEK-1-associated UPRer activation.},
journal = {Biochemical and biophysical research communications},
volume = {828},
number = {},
pages = {154071},
doi = {10.1016/j.bbrc.2026.154071},
pmid = {42259196},
issn = {1090-2104},
abstract = {Alzheimer's disease (AD) is the leading cause of dementia with no effective disease-modifying treatments. Here, we found that Escherichia coli (E. coli) DH5α relieved learning defects and paralysis, and prolonged lifespan in amyloid-β (Aβ)-expressing C. elegans. DH5α inhibited Aβ aggregation via activating the PEK-1-dependent endoplasmic reticulum unfolded protein response (UPRer). We further identified equol from DH5α metabolites, which alleviated AD-related phenotypes through the same PEK-1/UPRer pathway.},
}

@article {pmid42259394,
year = {2026},
author = {Zhang, K and Kong, S and Ma, Y and Kan, C and Zheng, T and Sun, X},
title = {Natural Monomer Compounds in Neurodegenerative Diseases: Targeting Ferroptosis and Neuroinflammation.},
journal = {Behavioural brain research},
volume = {},
number = {},
pages = {116319},
doi = {10.1016/j.bbr.2026.116319},
pmid = {42259394},
issn = {1872-7549},
abstract = {Neurodegenerative diseases (NDDs), including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, are characterized by progressive neuronal loss driven by oxidative stress, mitochondrial dysfunction, and chronic neuroinflammation. Ferroptosis, an iron-dependent and lipid peroxidation-associated form of regulated cell death, has recently been identified as a key contributor to neuronal vulnerability. Emerging evidence demonstrates that purified natural monomer compounds derived from medicinal plants exert potent neuroprotective effects by targeting ferroptosis and neuroinflammatory pathways. Representative agents such as curcumin, baicalin, resveratrol, and ginsenoside Rg1 activate nuclear factor E2-related factor-2 and glutathione peroxidase 4 signaling to preserve redox balance, while suppressing microglia-mediated inflammation through inhibition of toll-like receptor 4 pathways. This review highlights the interplay between ferroptosis and neuroinflammation in NDDs, summarizes the regulatory effects of bioactive herbal monomer compounds, and discusses recent advances in multi-omics profiling, nano-delivery strategies, and translational research. By modulating the ferroptosis-neuroinflammation axis, these compounds may represent promising therapeutic candidates for NDDs.},
}

@article {pmid42259474,
year = {2026},
author = {Ma, Z and Yang, Z and Xiao, Z and Huang, B and Wang, X},
title = {Unveiling the Multi-Target Mechanisms of Zuo Gui Wan in Alzheimer's Disease: An Integrated Study Combining Network Pharmacology, Mendelian Randomization, and Molecular Docking.},
journal = {Brain research bulletin},
volume = {},
number = {},
pages = {111972},
doi = {10.1016/j.brainresbull.2026.111972},
pmid = {42259474},
issn = {1873-2747},
abstract = {PURPOSE: Zuo Gui Wan (ZGW), a traditional Chinese medicine formula, shows neuroprotective potential, but the mechanisms underlying its therapeutic effects on Alzheimer's disease (AD) remain unclear. This study aims to identify the active components, molecular targets, and biological pathways of ZGW in AD using an integrated systems pharmacology approach combining network analysis and causal inference.

METHODS: Active ZGW ingredients and targets were sourced from TCMSP and BATMAN-TCM. Summary-data-based Mendelian Randomization (SMR) and colocalization analyses integrated eQTL and AD GWAS data to identify gene-AD associations. Network pharmacology, GO/KEGG enrichment, PPI analysis, and molecular docking were conducted. Selected targets were examined by CCK-8 assay and Western blot in an Aβ25-35-induced SH-SY5Y neuronal injury model treated with ZGW-containing rat serum.

RESULTS: We identified 134 bioactive ZGW compounds targeting 391 AD-related genes. SMR prioritized six targets (ACE, SRC, STAT1, LEP, EGFR, and MAPK3) associated with neuroinflammatory and cardiovascular pathways. Molecular docking suggested strong interactions between key compounds and targets, notably berberine with SRC (-10.53kcal/mol) and compound 1 (PubChem CID: 137704703) with MAPK3 (-17.22kcal/mol). In the Aβ-induced neuronal model, ZGW-containing serum partially restored cell viability, reduced ERK1/2 and STAT1 phosphorylation, and increased ACE expression.

CONCLUSION: Integrated computational analyses prioritized six potential AD-related targets of ZGW, including ACE, SRC, STAT1, LEP, EGFR, and MAPK3. Preliminary cellular experiments further supported the involvement of MAPK3/ERK and STAT1 signaling, with increased ACE expression observed after ZGW treatment. These findings provide mechanistic insight into the potential therapeutic effects of ZGW in AD.},
}

@article {pmid42259543,
year = {2026},
author = {Nelson, MB and Crecelius, C and Jones, AP and Coffey, C and Dasgupta, A},
title = {Correlation of CSF Biomarkers with Cognitive Screening Tests and PET Scan: A Tandem Approach.},
journal = {Annals of clinical and laboratory science},
volume = {56},
number = {2},
pages = {139-143},
pmid = {42259543},
issn = {1550-8080},
abstract = {OBJECTIVE: Testing for amyloid beta protein (Aβ42), total tau (t-Tau), and phosphorylated tau (p-Tau at position 181: p-Tau 181) in CSF using Roche Elecsys assays has been approved by the FDA as biomarkers for Alzheimer's disease. We studied correlation between pTau181/Aβ42 ratios (>0.023 positive cutoff), screening for cognitive functions (commonly used for screening patients suspected of dementia and AD) with actual AD diagnosis based on PET scans in 143 patients.

METHODS: All Roche Elecsys (electrochemiluminescence) assays for biomarkers were run on Cobas e 801 analyzer. Imaging studies were performed using fluorodeoxyglucose PET scans. Screening patients for cognitive functions (SCFs) included either MOCA, SLUMS, STMS, or MMSE.

RESULTS: Out of 143 patients with CSF AD biomarker ratios studied, 80 patients showed positive values (mean: 0.0555), while 63 patients showed negative ratios (mean: 0.0138). We also compared biomarker results with PET imaging in 40 patients (PET scan results were not available for all patients). Chi-square analysis showed a statistically significant association between positive CSF biomarker tests and PET scans {X[2](1, N=40)=14.593; p<0.01}.
In contrast, we observed poor correlation between SCFs and PET scan results using chi-square analysis {X[2](1, N=40)=3.558, p=0.059}.
However, binary logistic regression demonstrated a combination of abnormal SCF and a positive CSF screen significantly predicted a positive imaging result {X[2](2, N=40)=15.940, p<.001}.


CONCLUSIONS: CSF pTau181/Aβ42 ratios correlated significantly better with PET scan findings compared to various SCFs. Furthermore, a combination approach that included SCF and CSF biomarkers provided better correlation with positive PET imaging.},
}

@article {pmid42259598,
year = {2026},
author = {Xu, L and Jiang, Q and Jin, Y and Lin, T and Cao, R and Xu, HD and Liu, X and Yang, Z and Zhan, W and Liang, G},
title = {A [19]F MRI/NIR-FL Nanoprobe for "Turn-On" Imaging of β-Secretase (BACE1) Activity in Alzheimer's Disease.},
journal = {Angewandte Chemie (International ed. in English)},
volume = {},
number = {},
pages = {e1325073},
doi = {10.1002/anie.1325073},
pmid = {42259598},
issn = {1521-3773},
support = {2023YFF0724100//National Key Research and Development Program of China/ ; 22504126//National Natural Science Foundation of China/ ; 22234002//National Natural Science Foundation of China/ ; BK20250927//Natural Science Foundation of Jiangsu Province/ ; BK20232007//Natural Science Foundation of Jiangsu Province/ ; JSSCTD202409//Jiangsu Shuang Chuang Team/ ; 2025M771069//China Postdoctoral Science Foundation/ ; //Zhishan Young Scholar Program of Southeast University/ ; },
abstract = {Alzheimer's disease (AD) is the most common progressive neurodegenerative disorder with very few therapeutic methods; thus, its early detection is urgently important. β-secretase (BACE1) is a well-recognized biomarker of early-stage AD, but its in vivo imaging-based diagnostic method is rarely reported. Herein, we report a BACE1-disassemblable nanoprobe, [19]F-Cy5.5-NP for "Turn-On" [19]F magnetic resonance/near-infrared fluorescence ([19]F MR/NIR-FL) imaging of the enzyme activity in AD in vivo. The "Turn-On" [19]F MRI signals are employed for imaging BACE1 activity with high specificity, while the "Turn-On" NIR-FL signals are used for double checking the enzyme activity with high spatial resolution. Specifically, [19]F-Cy5.5-NP, with a silent [19]F MR/NIR-FL signal is obtained from the precursor Cys(StBu)-Glu-Val-Asn-Leu-Asp-Ala-Glu-Phe(CF3)-Lys(Cy5.5)-CBT ([19]F-Cy5.5) through a CBT-Cys click reaction. Upon BACE1 cleavage, the nanoprobe disassembles, resulting in 6.8 ± 1.3-fold and 9.5 ± 0.3-fold increases of [1] [9]F NMR and NIR-FL signals in vitro, respectively. Moreover, [19]F-Cy5.5-NP renders 4.6 ± 0.9-fold/1.5 ± 0.1-fold higher [19]F MRI/NIR-FL signal in Aβ25-35-treated PC12 cells than that in normal PC12 cells. In vivo experimental results show that this nanoprobe enables the precise imaging of BACE1 activity in AD zebrafish models. We anticipate that [19]F-Cy5.5-NP could be applied for the early diagnosis of AD in clinics in the future.},
}

@article {pmid42259955,
year = {2026},
author = {Domingo, JL},
title = {Aging in a highly polluted world: challenges and solutions to prevent Alzheimer's disease.},
journal = {Archives of toxicology},
volume = {},
number = {},
pages = {},
pmid = {42259955},
issn = {1432-0738},
abstract = {Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder globally and a leading cause of disability and death among the elderly. As populations age worldwide, the epidemiological burden of AD is expected to more than double by 2050, surpassing 150 million affected individuals. While genetic susceptibility, particularly the apolipoprotein E ε4 (APOE4) allele, modulates individual risk, most AD cases are late-onset and shaped by complex interactions between genetic background and modifiable environmental exposures. Environmental pollution has emerged as a critical and potentially preventable contributor to this burden. The 2024 Lancet Commission on Dementia Prevention, Intervention, and Care has identified 14 modifiable risk factors, with air pollution explicitly included. Drawing on evidence from human epidemiological cohorts, experimental animal models, and in vitro neuronal/glial systems, the present review aims to synthesize mechanistic evidence linking environmental pollutant classes to AD-relevant neuropathology. The review examines the growing body of evidence linking major categories of environmental pollutants (ambient particulate matter, heavy metals, pesticides, PFAS, and emerging contaminants including microplastics and nanoplastics) to AD risk and pathogenesis. Special attention is given to studies showing that the characteristic neuropathological features of AD may emerge in children and young adults chronically exposed to heavily polluted urban environments, which highlights critical concerns about when and how these changes develop throughout life. Shared mechanistic pathways through which environmental pollutants promote neurodegeneration are discussed, including neuroinflammation, oxidative stress, blood-brain barrier disruption, tau kinase dysregulation, epigenetic reprogramming, and gut-brain axis dysbiosis. The review also examines the amplifying role of biological aging on neurotoxic vulnerability and proposes a comprehensive, multi-level prevention framework addressing individual exposure reduction, clinical risk identification, and population-level policy interventions.},
}

@article {pmid42259980,
year = {2026},
author = {Basri, R and Al-Kuraishy, HM and Alruwaili, M and Al-Gareeb, AI and Albuhadily, AK and Alexiou, A and Papadakis, M and Faheem, SA and Batiha, GE},
title = {Bile acids in Alzheimer's disease: a double-edged sword in gut-liver-brain signaling and neurodegeneration.},
journal = {Naunyn-Schmiedeberg's archives of pharmacology},
volume = {},
number = {},
pages = {},
pmid = {42259980},
issn = {1432-1912},
abstract = {Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-β (Aβ) deposition, tau pathology, synaptic dysfunction, neuroinflammation, and metabolic impairment. Increasing evidence suggests that bile acids, traditionally recognized for their roles in lipid digestion and hepatic metabolism, act as endocrine signaling molecules that influence central nervous system (CNS) homeostasis. Through enterohepatic circulation and microbiota-dependent biotransformation, bile acid composition is dynamically regulated and can modulate peripheral metabolic and immune pathways with downstream effects on the brain. Notably, bile acid signaling via key receptors such as the farnesoid X receptor (FXR) and the Takeda G protein-coupled receptor 5 and G-protein-coupled bile acid receptor 1 (TGR5/GPBAR1) has emerged as a mechanistic bridge linking liver-gut physiology to neuroinflammatory and neurodegenerative processes. Altered bile acid profiles have been reported in AD and mild cognitive impairment, with accumulating findings suggesting that hydrophobic secondary bile acids may contribute to blood-brain barrier (BBB) disruption and neurotoxicity. In contrast, hydrophilic bile acids may exert neuroprotective and anti-inflammatory effects. In addition, bile acids drive the release of gut hormones such as glucagon-like peptide 1 (GLP-1) and fibroblast growth factor 19 (FGF19), highlighting indirect neurometabolic pathways relevant to cognition and neurodegeneration. This narrative review synthesizes current biochemical, experimental, and clinical evidence supporting a role for bile acid signaling in AD pathogenesis and progression. We discuss receptor-mediated pathways, microbiota-bile acid interactions, neuroimmune modulation, and translational perspectives, proposing that bile acid-based biomarkers and therapeutic strategies targeting FXR/TGR5 signaling may represent promising avenues for future AD intervention.},
}

@article {pmid42260160,
year = {2026},
author = {El-Ghazawi, K and Aberra, YT and Veeramasu, Y and Fares, WA and Isakson, BE and Sontheimer, H and Eyo, UB and Peirce, SM},
title = {Transcriptional analyses identify pericyte-centered signaling programs altered by sex and brain region in Alzheimer's Disease.},
journal = {Communications biology},
volume = {},
number = {},
pages = {},
doi = {10.1038/s42003-026-10446-y},
pmid = {42260160},
issn = {2399-3642},
abstract = {Pericytes are critical components of the neurovascular unit (NVU), regulating endothelial cell stability, blood-brain barrier (BBB) integrity, and neuroimmune signaling. Their role in Alzheimer's Disease (AD), particularly regarding sex differences and brain region specificity, remains poorly defined. Using single-nucleus RNA sequencing analysis and cell-cell communication tools (LIANA, Tensor-cell2cell), we characterize pericyte transcriptional and signaling changes across the middle temporal gyrus (MTG) and dorsolateral prefrontal cortex (DLPFC) of AD and non-AD donors stratified by sex. We identify a pericyte-endothelial TGFβ signaling program upregulated in female AD donors specifically in the MTG, and a downregulated estrogen pathway involving pericyte-astrocyte ligand-receptor interactions, supported by increased pericyte-astrocyte separation in spatial transcriptomics. We also identify a microglia-to-pericyte program enriched for hypoxia and p53 pathways that is elevated in both sexes with regional specificity. Our findings implicate pericyte-driven communication as a mechanistic contributor to female-biased AD vulnerability, and support sex- and region-aware approaches in neurodegeneration research.},
}

@article {pmid42260188,
year = {2026},
author = {Aldaghi, M and Khatir, AA and Sepidarkish, M and Arjmandi, D and Mousavi, F and Aghapour, S and Bayani, M and Rostami, A},
title = {Association between Toxoplasma gondii seropositivity and Alzheimer's disease: a case-control study.},
journal = {Parasitology research},
volume = {},
number = {},
pages = {},
doi = {10.1007/s00436-026-08711-4},
pmid = {42260188},
issn = {1432-1955},
abstract = {Alzheimer's disease (AD) is a progressive neurodegenerative condition marked by declining cognitive function and memory deterioration. Emerging evidence suggests that infectious agents, including Toxoplasma gondii, may contribute to the risk of developing this disorder. Because previous studies on this association have produced limited and inconsistent results, we examined the link between T. gondii infection and Alzheimer's disease. This case-control study included 90 recently diagnosed AD patients from Ayatollah Rouhani Hospital and Clinic in Babol, Iran, and 91 healthy individuals as controls. After obtaining written informed consent, serum samples were collected from both groups. AD was determined through expert clinical evaluation, and the Mini-Mental State Examination (MMSE) was used to assess cognitive status and disease severity. Anti-T. gondii IgG antibodies were detected using ELISA. Data were analyzed in SPSS using chi-square tests, and odds ratios with 95% confidence intervals were calculated. The seroprevalence of T. gondii was 77.7% in cases and 89.0% in healthy controls. T. gondii seropositivity showed a significant inverse association with AD in both univariate analysis (OR: 0.43, 95% CI: 0.18-0.98; P = 0.04) and multivariate analysis (OR: 0.35, 95% CI: 0.14-0.92; P = 0.03). Additionally, T. gondii seropositivity was significantly associated with lower odds of greater AD severity in multivariate analysis (OR: 0.44, 95% CI: 0.20-0.97; P = 0.04). Our findings suggest an inverse association between T. gondii seropositivity and AD. Moreover, seropositivity was associated with lower odds of more severe disease. Further research is warranted to clarify the biological basis and clinical significance of this association.},
}

@article {pmid42260217,
year = {2026},
author = {Kodi, T and Nandakumar, K and Kishore, A},
title = {AMPK-NLRP3 Inflammasome Crosstalk: Structural Insights, Molecular Mechanisms, and Therapeutic Implications for Inflammation and Neuroinflammation.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {},
pmid = {42260217},
issn = {1559-1182},
abstract = {The nucleotide-binding domain leucine-rich repeat and pyrin domain-containing protein-3 (NLRP3) inflammasome plays a central role in inflammatory diseases, including cardiovascular, gastrointestinal, neurodegenerative, autoimmune, hepatic, renal, and pulmonary disorders. Although various cellular pathways tightly regulate its activation, the precise mechanisms remain unclear. Emerging evidence highlights adenosine monophosphate-activated protein kinase (AMPK) as a critical regulator of energy balance and cellular metabolism, suggesting its potential involvement in modulating NLRP3 inflammasome activity. This review explores the structural dynamics of the NLRP3 inflammasome and the activation of AMPK signaling. It focuses on the mechanistic pathways underlying AMPK-mediated suppression of the NLRP3 inflammasome, including autophagy-dependent regulation, sirtuin-mediated regulation, ER stress/TXNIP signaling pathway, regulation of mitochondrial homeostasis, NF-κB/MyD88-mediated priming, and maintenance of lysosomal integrity. Furthermore, the review discusses the interplay of these pathways in CNS-specific disease models, such as Ischemic stroke/cerebral ischemia, Alzheimer's disease, Parkinson's disease, multiple sclerosis, diabetic neuropathy, and neuroinflammation models, as well as traumatic brain injury, streptozotocin-induced neuroinflammation, and lipopolysaccharide-induced neuroinflammation. Additionally, this review examined therapeutic strategies targeting the AMPK-NLRP3 axis in neuroinflammatory and neurodegenerative disorders.},
}

@article {pmid42260290,
year = {2026},
author = {Monteverdi, A and Ramusino, MC and Conca, F and Manzon, S and Redolfi, A and Lupi, E and De Grazia, M and Lorenzi, RM and Gaviraghi, M and Mazzocchi, L and Farina, LM and Costa, A and Pichiecchio, A and Cappa, SF and Wheeler-Kingshott, CAMG and Palesi, F and D'Angelo, E},
title = {Alterations in topological and dynamical parameters correlate with disease biomarkers and neuropsychological scores in prodromic stages of dementia.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-56387-8},
pmid = {42260290},
issn = {2045-2322},
abstract = {Mild cognitive impairment (MCI) is a clinical condition at the very beginning of dementia continuum whose heterogeneity prevents a precise prediction of clinical evolution. In this work, in a cohort composed of MCI, healthy controls (HC), and Alzheimer's disease (AD) patients, graph theory (GT) was combined with virtual brain modelling (TVB) to extract the information on network topology and dynamics embedded in magnetic resonance imaging data. With this approach, the analysis was extended to a multiparametric space and brought from the group to the subject-specific level. The comparison of network properties in HC, MCI, and AD revealed a profound reshaping of brain connectivity, which mainly affected the default mode, limbic, attention, and somatosensory networks. Interestingly, positivity to AD biomarkers (Aβ and τ) in MCI correlated with network topology, while a TVB parameter (i.e., recurrent excitation) correlated with reduced global cognition (MMSE score). The combination of GT and TVB parameters was superior to the individual techniques alone in providing a subject-specific phenotype of MCI sensitive to molecular biomarkers and correlated (R[2] ~ 70%) with neuropsychological scores. This, in turn, could form the basis for a more precise stratification in prodromic dementia leading, in future, to a personalized prediction of evolution and therapeutic intervention.},
}

@article {pmid42260548,
year = {2026},
author = {Canal, C and Aguilar, K and Comes, G and Sanz, E and Giralt, M and Sanchis, P and Hidalgo, J},
title = {Chronic central-targeted Interleukin-6 overexpression promotes hippocampal and cortical neuropathology in the Tg2576 mouse model of Alzheimer's disease.},
journal = {Alzheimer's research & therapy},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13195-026-02101-9},
pmid = {42260548},
issn = {1758-9193},
support = {PID2021-126602OB-I00//Ministerio de Ciencia e Innovación y Fondo Europeo de Desarrollo Regional/ ; SAF2014-56546-R//Ministerio de Economía y Competitividad y Fondo Europeo de Desarrollo Regional/ ; RTI2018-101105-B-I00//Ministerio de Ciencia, Innovación y Universidades y Fondo Europeo de Desarrollo Regional/ ; },
abstract = {BACKGROUND: Interleukin-6 (IL-6) is a cytokine detected in the brains and peripheral fluids of both Alzheimer's disease (AD) patients and mouse models, where its levels correlate with amyloid-beta (Aβ) burden and plaque deposition. Interestingly, IL-6 deficiency ameliorates cognitive deficits and attenuates hippocampal neuroinflammation, whereas astrocyte-targeted IL-6 signaling via its soluble receptor accentuates pathological features in AD mouse models. These findings suggest that central IL-6 overexpression may actively drive disease manifestations. However, because IL-6 can also signal through its classical membrane-bound receptor pathway, the overall impact of central IL-6 on AD pathophysiology is still not fully elucidated.

MAIN TEXT: To explore the contribution of central IL-6 overexpression in modulating AD-related mortality, metabolic, behavioral and neuroinflammatory changes in the hippocampus and cortex, we crossed a transgenic mouse model (Tg2576) of Aβ-driven amyloidosis with mice expressing IL-6 under the Glial Fibrillary Acidic Protein promoter (GFAP-IL6), which predominantly targets astrocytes. Chronic IL-6 overexpression reduced inguinal white adiposity in both males and females and decreased body weight in females. Early behavioral alterations were observed in Tg2576 mice, with central-targeted IL-6 overexpression regulating behavior in an age- and sex-dependent manner. Increased cortical and hippocampal Aβ42/Aβ40 ratios, along with gliosis, were observed in aged female and male Tg2576 mice. Interestingly, chronic central-targeted IL-6 overexpression increased cortical and hippocampal Aβ42/Aβ40 ratios while inducing a differential distribution and/or reactivity of astrocytes and microglia in aged Tg2576 mice. In particular, central-targeted IL-6 overexpression resulted in increased overall gliosis in the cortical and hippocampal parenchyma but reduced gliosis in the vicinity of cortical and hippocampal amyloid plaques. Finally, cortical transcriptomic profiling in Tg2576 mice revealed widespread changes in immune, synaptic, and stress response pathways in response to chronic IL-6 overexpression, with cortical neuroinflammatory and neurotransmission-associated gene networks showing sex-dependent differences.

CONCLUSIONS: Our findings emphasize that chronic central-targeted IL-6 overexpression shapes the cortical and hippocampal molecular landscape underlying amyloidosis in both male and female Tg2576 mice. Thereby, we propose IL-6 as a potential target for future AD therapeutic strategies.},
}

@article {pmid42260566,
year = {2026},
author = {Ullah, F and Du, S and Jin, W and Nagar, YA},
title = {Disintegrating ipseity: a gerontological exegesis of Alzheimer's disease and relational identity in Alice Munro's fiction.},
journal = {Philosophy, ethics, and humanities in medicine : PEHM},
volume = {21},
number = {1},
pages = {},
pmid = {42260566},
issn = {1747-5341},
abstract = {BACKGROUND: Alzheimer's is a progressive disorder of the brain that gradually affects memory, personality, behaviour, identity, and interpersonal relationships, particularly among older adults. Alice Munro's novella "The Bear Came Over the Mountain" offers a compelling literary framework for exploring these impacts through narrative gerontology, a lens that emphasizes storytelling's role in shaping identity and relational bonds during ageing and illness.

METHOD: This study applies narrative gerontology to analyze Munro's depiction of Alzheimer's, focusing on the experiences of Fiona and Grant. Through detailed textual analysis, it examines the gerontological concept of "we-narrative" (shared relational identity) to understand how identity, memory loss, and relational dynamics evolve.

RESULTS: Munro portrays Alzheimer's as both a medical condition and a social experience, fragmenting Fiona's sense of self and reshaping the couple's shared identity. Fiona's fading memories unravel her narrative, diminishing her autonomy, while Grant's shift from husband to caregiver redefines their relationship. The novella's disjointed structure reflects the cognitive chaos of Alzheimer's, deepening its emotional impact. The gerontological "we-narrative," representing shared relational identity, reveals the enduring strength of their bond, as Grant's selfless actions highlight a transformed expression of love.

DISCUSSION: Dementia narrative features how caregivers' identity gradually forms through the lived experience of supporting a loved one with cognitive decline. These findings align with narrative gerontology's view that stories help individuals and caregivers navigate identity and loss. Munro's work challenges stereotypes about ageing, emphasizing the emotional complexity of caregiving and the resilience of human connections.

CONCLUSION: Munro's novella powerfully illustrates Alzheimer's multifaceted effects, using narrative to explore identity, care, and relational adaptation in the context of ageing and illness.},
}

@article {pmid42260606,
year = {2026},
author = {Ferreira Dos Santos, L and Cozachenco, D and Lima-Filho, RAS},
title = {Corticothalamic circuit and executive dysfunction in Alzheimer's disease and related tauopathies.},
journal = {The Journal of physiology},
volume = {},
number = {},
pages = {},
doi = {10.1113/JP291604},
pmid = {42260606},
issn = {1469-7793},
support = {3300382483424060//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; E-26/200.054/2024//Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro/ ; E-26/200.203/2024//Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro/ ; },
}

@article {pmid42260770,
year = {2026},
author = {Dushyant, and Nayak, S and Panchal, V and Narwal, S and Singh, J and Dhingra, AK and Sakshi, and Kaur, J and Yadav, N and Saini, J},
title = {Formulation, Development, and In vitro Evaluation of Sustained Release Buccal Films for Optimized Memantine Therapy.},
journal = {Drug metabolism and bioanalysis},
volume = {},
number = {},
pages = {},
doi = {10.2174/0131173853466482260428064458},
pmid = {42260770},
issn = {3117-3861},
abstract = {INTRODUCTION: Memantine, an N-methyl-D-aspartate (NMDA) receptor antagonist, is employed in moderate to severe Alzheimer's disease but has the disadvantage of low oral bioavailability owing to first-pass metabolism and multiple doses. Buccal drug delivery is one such alternative that has received attention for enhancing systemic availability and patient compliance.

METHODS: Sustained-release buccal films of memantine hydrochloride were prepared by the solvent casting technique using Hydroxypropyl Methylcellulose (HPMC) and Carbopol 940 as film-forming and mucoadhesive polymers, polyethylene glycol 400 as plasticizer, and menthol as permeation enhancer. UV and FTIR were used for preformulation studies and for compatibility testing. The films were assessed for their physicochemical properties, tensile strength, swelling studies, surface pH, drug content, residence time, and in vitro release. Optimization of the result was carried out by statistical regression analysis with Design Expert® software.

RESULTS: The prepared films possessed uniform thickness, good mechanical properties, surface pH compatible with the buccal mucosa, and provided constant drug release for 8 h. FTIR studies revealed that there was no chemical incompatibility between memantine and excipients. F11 was found to have the highest drug content (90.1%), a good swelling index (19.4%), good folding endurance, and a conducive residence time of approximately 5 h.

DISCUSSION: The sustained release and the positive mucoadhesive properties observed are in line with those reported for other buccal film systems. The swelling profile and drug release kinetics were markedly affected by the polymer concentration.

CONCLUSION: The developed sustained-release buccal films of memantine hydrochloride demonstrated favorable physicochemical and in vitro release characteristics, indicating their potential as a noninvasive alternative drug delivery system. Although buccal administration is theoretically capable of bypassing hepatic first-pass metabolism and improving systemic availability, such benefits could not be conclusively established in the absence of in vivo pharmacokinetic and ex vivo permeation studies. Therefore, further investigations are required to validate these potential advantages.},
}

@article {pmid42260778,
year = {2026},
author = {Singh, H and Singh, BK and Kumar, A and Chauhan, K and Chauhan, B and Kumar, A and Mishra, AK and Chopra, S and Agarwal, V and Chopra, H and Greig, NH},
title = {Exploring the Cellular and Molecular Mechanisms Underlying Alzheimer's Disease Utilizing Cerebral Organoids Derived from Patient-specific Induced Pluripotent Stem Cells (iPSCs): A Review with Implications for Surgical Interventions.},
journal = {Current neuropharmacology},
volume = {},
number = {},
pages = {},
doi = {10.2174/011570159X428563260430050900},
pmid = {42260778},
issn = {1875-6190},
abstract = {Alzheimer's disease (AD) remains a major unmet medical need characterized by progressive cognitive decline and multifactorial pathology. Induced pluripotent stem cell (iPSC) technology provides an invaluable platform to model patient-specific and late-onset disease mechanisms. Advances in reprogramming strategies and neuronal differentiation protocols have improved the fidelity of human-derived neuronal models by preserving age-related and epigenetic features relevant to AD. Cortical organoids generated from iPSCs have further enabled the reconstruction of three-dimensional brain-like structures, facilitating the study of amyloid and tau pathology, synaptic dysfunction, and neuroinflammatory interactions in a physiologically relevant context. Ongoing innovations, such as microglial integration, vascularization, and induction of cellular aging, continue to enhance the translational accuracy of these models. iPSC and organoid systems are increasingly used for mechanistic dissection of AD-related pathways, genotype-phenotype correlations, and high-throughput therapeutic screening. Nevertheless, challenges related to reproducibility, maturation, and scalability remain barriers to clinical translation. The review also highlights ethical, regulatory, and societal considerations inherent to human stem cell-based disease modeling. Together, these developments underscore the transformative potential of iPSC-derived models in advancing mechanistic understanding and therapeutic discovery for Alzheimer's disease.},
}

@article {pmid42260779,
year = {2026},
author = {Kong, W and Su, P and Xu, Y and Wang, S and Wei, K and Ke, F and Wen, G and Yu, Y},
title = {Multitask Sparse Canonical Correlation Analysis and Regression with Parameter Decomposition based on Deep Subspace Reconstruction for Alzheimer's Disease.},
journal = {Current Alzheimer research},
volume = {},
number = {},
pages = {},
doi = {10.2174/0115672050449671260513065443},
pmid = {42260779},
issn = {1875-5828},
abstract = {INTRODUCTION: Multimodal imaging genomics overcomes the limitations of singlemodality analyses, offering a more comprehensive understanding of brain pathophysiology. Traditional methods like sparse canonical correlation analysis (SCCA) and its improved versions have been widely used to identify key brain regions and single nucleotide polymorphisms (SNPs) associated with neurodegenerative diseases, such as Alzheimer's disease (AD). However, the fusion of complex and heterogeneous multimodal neuroimages, along with the linear formulation of these methods, limits their ability to capture complex, nonlinear relationships in imaging-genetics data.

METHODS: To address this limitation, a novel framework, DSR-PDMTSCCAR, is introduced for multimodal AD data. This framework combines deep subspace reconstruction for nonlinear mapping and parameter decomposition to extract modality-consistent and modality-specific features across structural MRI (sMRI) and positron emission tomography (PET) data. Additionally, multitask sparse canonical correlation analysis (MTSCCA) is incorporated to capture correlations across multiple tasks, facilitating modeling of heterogeneous multimodal associations.

RESULTS: Evaluations on simulated datasets and the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort show that DSR-PDMTSCCAR outperforms conventional methods, including SCCA, partial least squares (PLS), and deep canonical correlation analysis (DCCA). The method identifies biomarkers such as hippocampal and amygdalar alterations in sMRI/PET and APOErelated genetic variants, all consistent with AD pathology.

DISCUSSION: The maximum canonical correlation coefficient (CCC) achieved was 0.1759, compared to 0.1525 for MTSCCA. The PET-SNP correlation (0.1896) was more than double that of MTSCCA (0.0864).

CONCLUSION: The DSR-PDMTSCCAR framework offers robust performance in multimodal imaging- genetics analysis, providing enhanced insights into AD pathophysiology and advancing precision medicine.},
}

@article {pmid42260810,
year = {2026},
author = {Cong, L and Ji, H and Yang, H and Kuang, G and Liu, H and Sun, H and Liu, Y},
title = {Causal effects of mental disorders on stroke subtypes: A proteome-wide Mendelian randomization and mediation analysis.},
journal = {Medicine},
volume = {105},
number = {23},
pages = {e49108},
doi = {10.1097/MD.0000000000049108},
pmid = {42260810},
issn = {1536-5964},
abstract = {Observational studies have demonstrated associations between mental disorders and stroke, yet causal relationships and potential molecular mechanisms remain elusive. To clarify this, we performed a bidirectional 2-sample Mendelian randomization (MR) analysis using genome-wide association studies summary statistics to assess the causal effects of 7 major mental disorders (schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorder, attention-deficit/hyperactivity disorder [ADHD], Alzheimer disease, and Parkinson disease) on stroke subtypes. Analyses were divided into discovery and validation cohorts of European ancestry, followed by MRlap and meta-analysis to obtain pooled estimates. To explore potential circulating protein mediators, 4907 plasma cis-protein quantitative trait loci (cis-pQTLs) from deCODE Genetics were screened, followed by Bayesian co-localization and 2-step MR mediation analyses. Our findings revealed that ADHD was consistently associated with an increased risk of any stroke (AS), any ischemic stroke (AIS), and particularly large-artery atherosclerotic stroke (LAS; odds ratio = 1.455; 95% confidence interval: 1.077-1.967). Mediators screening showed genetic liability to ADHD was linked to elevated circulating matrix metallopeptidase-12 (MMP12; β = 0.141, P = .005), which conferred protection against AIS and LAS, potentially lowering LAS risk by 7.5%. In conclusion, this MR study suggests ADHD is a causal risk factor for ischemic stroke, especially LAS. Paradoxically, circulating MMP12 acts as a protective mediator, modestly reducing this risk by 7.5%. These findings require validation in future experimental and cohort studies.},
}

@article {pmid42261077,
year = {2026},
author = {Fakorede, S and Cheng, K and Huang, CK and Martin, LE and Akinwuntan, AE and Burns, JM and Devos, H},
title = {The Effect of Postural Control on Attentional Resource Allocation in Alzheimer's Disease: An Event-Related Potential Study.},
journal = {Perceptual and motor skills},
volume = {},
number = {},
pages = {315125261459181},
doi = {10.1177/00315125261459181},
pmid = {42261077},
issn = {1558-688X},
abstract = {ObjectiveTo examine how the postural demand of quiet standing, compared to sitting, affects the allocation of attentional resources during a concurrent cognitive task in healthy older adults and individuals with Alzheimer's disease (AD).Methods87 healthy older adults (age 71.7 ± 4.2 years; MoCA 28.9 ± 1.1) and 16 individuals with AD (age 74.3 ± 5.1 years; MoCA 19.6 ± 6.3) completed a two-minute auditory novelty oddball task (50 stimuli: 80% frequent, 10% rare, 10% novelty) in both standing and sitting positions. Neural activity was recorded using electroencephalography (EEG). We used linear mixed models to compare P3 event-related potentials (ERPs) across groups and conditions, focusing on the P3b component (conscious stimulus evaluation) and the P3a component (automatic novelty detection). Behavioral outcomes were accuracy and reaction times on the oddball task, and sway velocity collected from a head-mounted accelerometer.ResultsA significant condition × group interaction was found for P3b latency in response to frequent stimuli (p = 0.003). While sitting, the AD group showed shorter P3b latencies than healthy older adults (p = 0.036). However, this pattern reversed under postural load: individuals with AD had significantly longer P3b latencies when standing compared to sitting (p = 0.01), whereas healthy older adults showed the opposite pattern, with significantly decreased latencies (p = 0.04). No significant effects were found for P3b amplitude or for the P3a component. Postural condition did not significantly impact behavioral outcomes in either group.ConclusionsQuiet standing may impose a selective neural cost on individuals with AD, reflected in slower conscious cognitive processing, while appearing to act as an arousing factor that facilitates faster processing in healthy older adults. Maintaining posture might require a reallocation of limited attentional resources that disrupts higher-order processing in AD.},
}

@article {pmid42261236,
year = {2026},
author = {Malvankar, A and Raut, M and Singh, SK and Singh, R and Mahindroo, N and Bajad, N},
title = {A comprehensive exploration of the structure-activity relationships, multitarget strategies, and therapeutic mechanisms of triazole scaffolds in Alzheimer's disease.},
journal = {Future medicinal chemistry},
volume = {},
number = {},
pages = {1-17},
doi = {10.1080/17568919.2026.2684615},
pmid = {42261236},
issn = {1756-8927},
abstract = {The deposition of the Aβ peptide extracellularly as diffused and neuritic plaques and intracellular hyperphosphorylated tau (p-tau) protein as neurofibrillary tangles (NFTs) are the key pathological changes observed in the progression of AD. Despite advances in the neuroscience research, the discovery and development of effective therapeutic agents have become challenging task for AD. The molecules modulating multiple targets involved in the disease attracted much attention as promising tools for the effective therapeutic efficacy. Triazole scaffold has been consistently rewarded as a promising versatile lead molecule with a pivotal position in modern medicinal chemistry. It has shown potent inhibitory activity against different targets involved in the progression of the AD including activity against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), amyloid beta (Aβ) accumulation, tau aggregation, neuroinflammation and oxidative stress. Recent reviews label 1,2,3-triazole as first choice scaffold for designing multifunctional hybrid molecules for AD. A comprehensive literature search was performed using PubMed, Scopus, Web of Science, and Google Scholar databases covering publications from 2000 to 2026. This review critically analyzes the evolution of triazole-based therapeutics from single-target cholinesterase inhibitors to modern multitarget-directed ligands. We systematically evaluate how the structural versatility of the 1,2,3- and 1,2,4-triazole cores facilitates interactions with key AD pathological hallmarks.},
}

@article {pmid42261248,
year = {2026},
author = {Choi, JS and Hur, JY},
title = {The Innate Immune Protein IFITM3 as a γ-Secretase Modulatory Protein: From Inflammation to Alzheimer's Disease.},
journal = {DNA and cell biology},
volume = {},
number = {},
pages = {10445498261456523},
doi = {10.1177/10445498261456523},
pmid = {42261248},
issn = {1557-7430},
abstract = {The mechanisms of Alzheimer's disease (AD) development are complex, and the detailed roles of neuroinflammation in AD still need to be elucidated. With various genetic and environmental risk factors, the accumulation of harmful amyloid plaques containing amyloid-β (Aβ) peptides is one of the main hallmarks of AD. Recent findings show that the innate immune protein interferon-induced transmembrane protein 3 (IFITM3) binds to γ-secretase and modulates Aβ production, providing a direct link between neuroinflammation, amyloidogenesis, and the pathogenesis of AD. In this review, we explore IFITM3-mediated modulation of γ-secretase complex activity and its pivotal role in AD pathology during neuroinflammation. Furthermore, we also provide an overview of the recent growing evidence connecting the roles of infection, the immune system, and AD pathogenesis.},
}

@article {pmid42261516,
year = {2026},
author = {Yoshida, Y and Tanito, M},
title = {Cognitive Assessment in Glaucoma Care: A Narrative Review of Clinical Rationale, Screening Tools, and Implementation Challenges.},
journal = {Cureus},
volume = {18},
number = {5},
pages = {e108458},
pmid = {42261516},
issn = {2168-8184},
abstract = {In recent years, increasing attention has been directed toward the association between glaucoma and cognitive impairment, with a growing number of reports highlighting their interrelationship. With the progression of population aging, the coexistence of these two conditions is expected to rise further. Cognitive impairment may influence glaucoma management in multiple ways, including difficulties in performing subjective examinations such as visual field testing, reduced adherence to topical medications, and an elevated risk of postoperative complications. Consequently, integrating cognitive assessment into glaucoma care may be particularly relevant in selected patient populations, such as older adults or those with suspected adherence or reliability issues. This narrative review aims to summarize the current evidence on the relationship between glaucoma and cognitive impairment and to provide an overview of commonly used cognitive screening tools. In addition, we discuss the clinical implications of cognitive dysfunction in glaucoma management and highlight emerging digital approaches for cognitive assessment. Given that much of the available evidence is observational and that glaucoma-specific validation of cognitive screening strategies remains limited, this review provides insights into optimizing glaucoma care in an aging society and outlines directions for future research.},
}

@article {pmid42261679,
year = {2026},
author = {Zauszniewski, JA and Burant, CJ and Almutairi, RR and Meyer, K and Irani, E},
title = {Use of Personal and Social Resourcefulness by Adult-Child and Spousal Caregivers of Persons with Dementia.},
journal = {International journal of aging & human development},
volume = {},
number = {},
pages = {914150261456742},
doi = {10.1177/00914150261456742},
pmid = {42261679},
issn = {1541-3535},
abstract = {PurposeThis study examined the use of personal and social resourcefulness when experiencing anger, anxiety, sadness, decision-making, and financial distress among adult-child and spousal caregivers of persons with dementia.MethodsBaseline data on 10 Resourcefulness Scale[©] items measuring personal and social resourcefulness in response to anger, anxiety, sadness, decision-making, and financial distress were obtained from 127 adult-child and 112 spousal caregivers of persons with dementia.ResultsAdult-child and spousal caregivers similarly used personal resourcefulness for financial distress (62%-68%) and both personal and social resourcefulness when angry (67%), sad (87%-92%), and making decisions (77%-98%). Spousal caregivers used both personal and social resourcefulness when anxious (37%), while adult-child caregivers used only personal resourcefulness (46%). The findings were similar across age, race, and gender subgroups.ConclusionsFuture research should explore the effects of other situational factors (e.g., caregiving burden) on resourcefulness. Gerontological healthcare professionals should assess the caregiver-care recipient relationship when determining and tailoring interventions.},
}

@article {pmid42252078,
year = {2026},
author = {Huang, Y and Xie, X and Huang, Z and Gangal, H and Chen, R and Wang, X and Li, J and Wang, J},
title = {Chronic Alcohol Exposure Produces Pathology-Dependent Corticostriatal Circuit Remodeling in Aβ- and Tau-Based Mouse Models of Alzheimer's Disease.},
journal = {Neuropharmacology},
volume = {},
number = {},
pages = {111069},
doi = {10.1016/j.neuropharm.2026.111069},
pmid = {42252078},
issn = {1873-7064},
abstract = {Chronic alcohol consumption is a major risk factor for Alzheimer's disease (AD), yet how alcohol exposure alters neural circuits under distinct pathological conditions remains poorly understood. Here, we used a humanized Aβ knock-in model (hAPP-KI) and a tauopathy model (PS19) to test how the same alcohol exposure affects distinct pathological contexts. In hAPP-KI mice, alcohol exposure increased cortical Aβ burden, enhanced excitatory synaptic transmission in the medial prefrontal cortex (mPFC), and reduced glutamatergic transmission from the mPFC to the dorsomedial striatum (DMS). In contrast, in PS19 mice, alcohol exposure increased tau phosphorylation and elevated mPFC-to-DMS glutamatergic transmission without altering local cortical excitatory input. Alcohol exposure was also associated with distinct microglial responses across pathological contexts. To assess microglial contributions to cortical excitatory regulation, we depleted microglia in wild-type mice and observed enhanced cortical glutamatergic transmission. Together, these findings suggest pathology-dependent circuit remodeling and microglial responses associated with alcohol exposure in AD models.},
}

@article {pmid42252207,
year = {2026},
author = {Ince, S and Van Hulle, C and Kollmorgen, G and Quijano-Rubio, C and Gleason, C and Bendlin, BB and Okonkwo, O and Asthana, S and Blennow, K and Zetterberg, H and Johnson, SC and Love, S and Miners, JS},
title = {Dysregulated TIE-2 expression is associated with blood-brain barrier leakiness and Alzheimer's disease-related neuropathology.},
journal = {Brain pathology (Zurich, Switzerland)},
volume = {},
number = {},
pages = {e70109},
doi = {10.1111/bpa.70109},
pmid = {42252207},
issn = {1750-3639},
support = {ARUK-SRF-2019A-001//Alzheimer's Research UK/ ; NIH R01AG027161//NIH National Center for Advancing Translational Sciences (NCATS)/ ; P50AG033514//NIH National Center for Advancing Translational Sciences (NCATS)/ ; R01AG054059//NIH National Center for Advancing Translational Sciences (NCATS)/ ; R01 AG062167/AG/NIA NIH HHS/United States ; UF1AG051216//NIH National Center for Advancing Translational Sciences (NCATS)/ ; UL1TR000427//NIH National Center for Advancing Translational Sciences (NCATS)/ ; //Ministry of National Education in Türkiye/ ; },
abstract = {Cerebral hypoperfusion and blood-brain barrier (BBB) leakiness are related to cognitive decline and the onset and spread of Aβ and tau pathology in Alzheimer's disease (AD). Disrupted angiopoietin/TIE (ANGPT/TIE) signalling causes neurovascular instability and BBB leakiness accelerating cognitive decline and disease pathology in mouse models of AD. To explore ANGPT/TIE signalling in human AD, we measured CSF TIE-1 and TIE-2 levels by ELISA in two independent clinical dementia cohorts, and serum and CSF Tie-1/-2 in paired CSF and serum samples from neurologically normal individuals. ANGPT1, ANGPT2, TIE-1 and TIE-2 levels were measured by ELISA in crude homogenate (CH) and microvessel-enriched fractions (MVFs) of post-mortem human parietal cortex in relation to biochemical markers of cerebral perfusion (MAG:PLP1) and BBB leakiness (parenchymal fibrinogen) in a control, AD, and vascular dementia (VaD) cohort. CSF soluble TIE-2 was elevated in AD biomarker+ve individuals and correlated positively with CSF t-tau and p-tau, and markers of BBB leakiness, neuronal injury, and neuroinflammation. Tissue TIE-2 levels were significantly reduced in Braak tangle stage (BS) III-IV, that is, brains with early-intermediate AD pathology, and were lower in MVFs in end-stage AD pathology (BSV-VI) than in controls or VaD. Lower levels of MVF TIE-2 correlated with markers of cerebral hypoperfusion and BBB leakiness. Our study reveals a reciprocal relationship between elevated CSF and reduced tissue TIE-2 expression that is related to markers of tau pathology, BBB leakiness, and cerebral hypoperfusion, providing novel insights into ANGPT/TIE signalling in AD.},
}