@article {pmid41033413,
year = {2025},
author = {Karakatsani, ME and Gezginer, I and Nozdriukhin, D and Tiemann, S and Yoshihara, HAI and Storz, R and Belau, M and Ni, R and Deán-Ben, XL and Razansky, D},
title = {Transcranial pulse stimulation modulates neuronal activity and functional network dynamics.},
journal = {Brain stimulation},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.brs.2025.09.021},
pmid = {41033413},
issn = {1876-4754},
abstract = {BACKGROUND: Transcranial pulse stimulation (TPS) has recently been proposed as a promising non-invasive technique for treating neurological disorders. While neuropsychological improvements in treated Alzheimer's disease (AD) patients support its safety and preliminary clinical effectiveness, the fundamental mechanisms of TPS action on the brain remain unclear.

OBJECTIVE: In this study, we explore the effects of TPS on neuronal activity and brain circuitry in healthy and AD mouse models.

METHODS: We utilized fluorescence calcium imaging combined with resting-state functional magnetic resonance imaging and c-Fos immunohistochemistry for validation. We performed wide-field fluorescent calcium imaging of TPS-treated mouse brains expressing genetically encoded calcium indicator in combination with resting state functional magnetic resonance imaging. The imaging data from AD mouse strains was compared to wild-type controls, followed by immunohistochemical analysis of neuronal activation to support the in vivo imaging findings.

RESULTS: TPS induced robust calcium influxes in GCaMP+ mice, increased c-Fos expression in the dentate gyrus, and rapidly but transiently reorganized functional connectivity across brain networks, particularly within the hypothalamus, hippocampus, and other limbic regions. At higher stimulation intensities, TPS is shown to trigger spreading depolarization waves.

CONCLUSION: These findings support the hypothesis that TPS-induced mechanical effects can effectively modulate brain activity while averting tissue heating and cavitation, thus shedding light on observed beneficial effects in patients and paving the way for further optimization of TPS as a therapeutic strategy for neurodegenerative diseases.},
}

@article {pmid41033139,
year = {2025},
author = {Javaid, S and Meng, Q and Wang, X and Ma, C and Duan, Y and Yang, S},
title = {Association Between Cognitive Functions and Bone Health in the Elderly: The NHANES, 2013-2014.},
journal = {Journal of clinical densitometry : the official journal of the International Society for Clinical Densitometry},
volume = {28},
number = {4},
pages = {101626},
doi = {10.1016/j.jocd.2025.101626},
pmid = {41033139},
issn = {1094-6950},
abstract = {We examined the association of cognitive function with bone mineral density (BMD), osteoporosis, and osteopenia. We identified 1070 participants (528 men) aged ≥60 years or older from the NHANES, 2013-2014. BMD was measured using dual-energy X-ray absorptiometry (DXA). Cognitive function was assessed using the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Word Learning sub-test, Animal Fluency test, and Digit Symbol Substitution Test (DSST). After adjusting for covariates, one standard deviation increase in the DSST score was associated with increased BMD of the total hip (β = 0.022, P = 0.007), femoral neck (β = 0.024 P = 0.004), and lumbar spine (β = 0.025, P = 0.005) in females. When comparing females in the highest quartile of the DSST score to those in the lowest quartile, the highest score group was associated with a lower risk of osteoporosis [odds ratio (OR), 0.25; 95 % CI, 0.09-0.70] and osteopenia [OR, 0.35 (0.16-0.76)]. No associations were found between the CERAD test, Animal Fluency test, and bone health in females, or between cognitive function and bone health in males. In conclusion, higher DSST scores were associated with higher BMD and lower risk of osteoporosis and osteopenia in elderly females.},
}

@article {pmid41033048,
year = {2025},
author = {McDermott, KE and Dieckhaus, L and Comrie, C and Sandrin, V and Hutchinson, EB and Barnes, CA},
title = {Microstructural changes in locus coeruleus-cortical projections in aged bonnet macaques are independent of myelin loss.},
journal = {Neurobiology of aging},
volume = {157},
number = {},
pages = {17-25},
doi = {10.1016/j.neurobiolaging.2025.09.009},
pmid = {41033048},
issn = {1558-1497},
abstract = {The locus coeruleus (LC) is a brainstem nucleus best known for being the primary site of noradrenaline production for the forebrain and is involved in the modulation and optimization of behavioral performance. The LC has many targets throughout the cortex, and ascending projections from the LC join the central tegmental tract (CTT), a well-defined white matter brainstem tract in the pons that terminates in the thalamus. Evidence indicates that the LC is one of the first brain regions to show pathological burden in Alzheimer's disease (AD), and AD patients exhibit structural alterations in the LC and its ascending projections. The extent to which changes occur in the LC and its projections in normal aging, however, is less clear. Analysis of LC-forebrain tractography has historically been difficult due to the small size of the LC as well as the abundance of crossing fibers in the brainstem. Ex vivo magnetic resonance imaging (MRI) allows us to overcome some of these setbacks, as longer scan times can be used to generate higher resolution images than is possible in live subjects. Here, we utilize a cohort of bonnet macaques, an excellent model of normative aging, and analyze the microstructure of the LC and its projections that join the CTT with respect to age. We have been able to overcome issues associated with LC tractography and have found a negative association with age and diffusivity.},
}

@article {pmid41032868,
year = {2025},
author = {Kim, SH and Hakun, JG and Li, Y and Harrington, KD and Elbich, DB and Sliwinski, MJ and Vandekerckhove, J and Oravecz, Z},
title = {Optimizing the Color Shapes Task for Ambulatory Assessment and Drift Diffusion Modeling: A Factorial Experiment.},
journal = {JMIR formative research},
volume = {9},
number = {},
pages = {e66300},
doi = {10.2196/66300},
pmid = {41032868},
issn = {2561-326X},
mesh = {Humans ; Female ; Middle Aged ; Aged ; Adult ; Male ; Aged, 80 and over ; *Memory, Short-Term/physiology ; Young Adult ; Smartphone ; *Neuropsychological Tests ; },
abstract = {BACKGROUND: Recent advances in cognitive digital assessment methodology, including high-frequency, ambulatory assessments, promise to improve the detection of subtle cognitive changes. Computational modeling approaches may further improve the sensitivity of digital cognitive assessments to detect subtle cognitive changes by capturing features that map onto core cognitive processes.

OBJECTIVE: We explored the validity of a brief smartphone-based adaptation of a visual working memory task that has shown sensitivity for detecting preclinical Alzheimer disease risk. We aimed to optimize properties of the task for computational cognitive feature extraction with drift diffusion modeling.

METHODS: We analyzed data from 68 participants (n=47, 69% women; n=55, 81% White; mean age 49, SD 14; range 24-80 years) who completed 60 trials for each of 16 variations of a visual working memory binding task (the Color Shapes task) on smartphones, over an 8-day period. A drift diffusion model was fit to the response time and accuracy data from the task. We experimentally manipulated 3 properties of the Color Shapes task (study time, probability of change, and choice urgency) to test how they yielded differences in key drift diffusion model parameters (drift rate, initial bias toward a response option, and caution in decision-making). We also evaluated how an additional task property, the test array size, impacted responses across all conditions. For array size, we tested a whole display of 3 shapes against a single probe of 1 shape only.

RESULTS: The 3 task property manipulations yielded the following results: (1) increasing the ratio of different responses was credibly associated with higher initial bias toward the different response (mean 0.06, SD 0.02 for the whole display; mean 0.15, SD 0.02, for the single probe condition); (2) increasing the choice urgency during the test phase was credibly associated with decreased caution in decision-making in the single probe condition (mean -0.04, SD 0.02) but not in the whole display (mean -0.01, SD 0.02); and (3) contrary to expectation, longer study times did not yield a credibly faster drift rate but produced credibly slower ones for the whole display condition (mean -0.28, SD 0.05) and a null effect for the single probe condition (mean 0.01, SD 0.05). In addition, as expected, we found that individual differences in drift rate were associated with age in both array sizes (r=-0.45 with Bayes factor=191), with older participants having a slower drift rate. Older participants also showed higher caution (r=0.42 with Bayes factor=80.76) in the single probe condition.

CONCLUSIONS: We identified a version of the Color Shapes task optimized for smartphone-based cognitive assessments in real-world settings, with data designed for analysis through computational cognitive modeling. Our proposed approach can advance the development of tools for efficient and effective early detection and monitoring of risk for Alzheimer disease.},
}

Humans
Female
Middle Aged
Aged
Adult
Male
Aged, 80 and over
*Memory, Short-Term/physiology
Young Adult
Smartphone
*Neuropsychological Tests

@article {pmid41032659,
year = {2025},
author = {Verberk, IMW and van Harten, AC and van der Flier, WM},
title = {Opposing views or like-minded? International Working Group and Alzheimer's Association criteria.},
journal = {Brain : a journal of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1093/brain/awaf366},
pmid = {41032659},
issn = {1460-2156},
}

@article {pmid41032625,
year = {2025},
author = {Rosenberg, GM and Murray, KA and Sawaya, MR and Jiang, YX and Geschwind, DH and Eisenberg, DS},
title = {Genetic and structural aspects of amyloid diseases.},
journal = {Science translational medicine},
volume = {17},
number = {818},
pages = {eadp3378},
doi = {10.1126/scitranslmed.adp3378},
pmid = {41032625},
issn = {1946-6242},
mesh = {Humans ; *Amyloidosis/genetics ; *Amyloid/chemistry/genetics/metabolism ; Mutation/genetics ; Animals ; },
abstract = {The conversion of proteins into insoluble fibrillar aggregates known as amyloid occurs in a wide variety of diseases, e.g., Alzheimer's disease, amyotrophic lateral sclerosis, systemic transthyretin amyloidosis, and multisystem atrophy. There are more than 60 disease-associated amyloid-forming proteins, and amyloid formation can occur sporadically or can be induced or accelerated by genetic mutations. This Review discusses structural mechanisms by which genetic changes promote amyloid formation and thereby influence disease outcomes. By dividing amyloid-forming proteins into six types according to the genetic mutations they carry and analyzing mutation-induced structural changes in amyloid fibrils, a better understanding of inheritance patterns of amyloid diseases (amyloidoses) can be obtained.},
}

Humans
*Amyloidosis/genetics
*Amyloid/chemistry/genetics/metabolism
Mutation/genetics
Animals

@article {pmid41032522,
year = {2025},
author = {Han, M and Han, Y and Jiang, Z and Gao, Y and Cao, G and Zhang, H and Wang, T and Li, Z},
title = {Ultrasmall inorganic nanoparticles repair damaged meningeal lymphatic vessels to boost Parkinson's disease therapy.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {122},
number = {40},
pages = {e2503434122},
doi = {10.1073/pnas.2503434122},
pmid = {41032522},
issn = {1091-6490},
support = {923741113 82472128//MOST | National Natural Science Foundation of China (NSFC)/ ; 2022YFA1104300//MOST | National Key Research and Development Program of China (NKPs)/ ; 22KJA310004//Major Basic Research Project of the Natural Science Foundation of the Jiangsu Higher Education Institutions (Key University of Science Research Project of Jiangsu Province)/ ; },
mesh = {Animals ; *Parkinson Disease/drug therapy/pathology/metabolism ; *Lymphatic Vessels/drug effects/pathology/metabolism ; Mice ; *Nanoparticles/chemistry ; Vascular Endothelial Growth Factor C/metabolism ; *Meninges/pathology/drug effects/metabolism ; Humans ; Mice, Inbred C57BL ; Male ; Disease Models, Animal ; Copper/chemistry/pharmacology ; },
abstract = {Meningeal lymphatic vessels (MLVs) have been identified to associate with various neurological diseases, such as traumatic brain injury (TBI), Alzheimer's disease (AD), Parkinson's disease, multiple sclerosis, and brain tumors. Damage to MLVs can exacerbate the pathological progression of these diseases and significantly impede therapeutic efficacy. Therefore, targeted repair of the damaged MLVs has emerged as an innovative strategy for treating these central nervous system (CNS) diseases. In this study, we find that inorganic Cu2-xSe nanoparticles, rather than conventional endogenous vascular endothelial growth factor-C (VEGF-C), can repair the damaged MLVs to restore their structure and functions. These nanoparticles not only promote the growth and development of lymphatic vessels but also enhance the drainage capacity of impaired MLVs, thereby facilitating the transport of immune cells and macromolecules through these vessels. Unlike the conventional repair of damaged MLVs, this is an instance where inorganic nanoparticles have been explored to stimulate the expression of VEGF-C and its receptor VEGFR3, thereby promoting the structural and functional recovery of these vessels. The enhanced drainage function of MLVs mediated by Cu2-xSe nanoparticles significantly alleviates the symptoms of pre-formed fibrils (PFFs)-induced Parkinson's disease in mice. Collectively, our findings demonstrate that inorganic nanoparticles can promote the growth and development of meningeal lymphatics like VEGF-C, providing a cost-effective and innovative strategy for repairing damaged MLVs to boost the therapeutic efficacy of CNS diseases.},
}

Animals
*Parkinson Disease/drug therapy/pathology/metabolism
*Lymphatic Vessels/drug effects/pathology/metabolism
Mice
*Nanoparticles/chemistry
Vascular Endothelial Growth Factor C/metabolism
*Meninges/pathology/drug effects/metabolism
Humans
Mice, Inbred C57BL
Male
Disease Models, Animal
Copper/chemistry/pharmacology

@article {pmid41032287,
year = {2025},
author = {Shean, J and White, K and Felten, K and O'Connor, V and Johnson, E and Fadel, M},
title = {Building States' Capacity to Address Dementia.},
journal = {The Gerontologist},
volume = {},
number = {},
pages = {},
doi = {10.1093/geront/gnaf226},
pmid = {41032287},
issn = {1758-5341},
abstract = {One of the principal objectives of the Building Our Largest Dementia Infrastructure (BOLD) program is to elevate dementia as a public health priority in state, local, territorial, and tribal health departments across the U.S. Since 2020, the BOLD program, through the stewardship of the Centers of Disease Control and Prevention, has supported 45 state and other health departments throughout the U.S. to refine and implement strategic public health action plans to address dementia that focus on risk reduction, early detection, and caregiving using the framework of the Healthy Brain Initiative Road Map Series. Following an overview and description of the extent of BOLD's reach, we will highlight several exemplars from individual states' work in advancing dementia as a public health priority, including efforts to engage local Geriatric Workforce Enhancement Programs to facilitate age-friendly local healthcare systems; working with diverse faith-based communities to disseminate risk reduction strategies; and supporting and training county staff to better meet the needs of dementia caregivers in their respective communities, among others. The resources, opportunities, and challenges to initiate key public health actions to address dementia vary widely across state, local, territorial, and tribal communities, and the current paper will demonstrate how CDC's BOLD Program has begun to address this rich diversity throughout the U.S.},
}

@article {pmid41032255,
year = {2025},
author = {Marks, B and Sisirak, J and Janicki, MP and Service, KP and Watchman, K},
title = {Advancing Inclusive Brain Health and Dementia Care for People with Intellectual and Developmental Disabilities: A Public Health Framework.},
journal = {The Gerontologist},
volume = {},
number = {},
pages = {},
doi = {10.1093/geront/gnaf222},
pmid = {41032255},
issn = {1758-5341},
abstract = {Adults with intellectual and developmental disabilities (IDD) face disproportionately high rates of chronic conditions, including an elevated risk for dementia. Yet access to appropriate brain health promotion and dementia care remains limited due to stigma, underdiagnosis, misdiagnosis, and systemic barriers. This article presents the Healthy Brain Initiative for People with Intellectual and Developmental Disabilities (HBI-PwIDD), which aims to: 1) raise awareness of brain health and support health-promoting approaches for people with IDD experiencing Alzheimer's disease and related dementias; 2) build interprofessional partnerships to develop an inclusive, competent workforce; and, 3) strengthen engagement of people with IDD and their supporters in accessing quality healthcare and improving outcomes. Applying a disability intersectionality lens, we integrate brain health promotion with dementia-capable services, emphasizing the critical role of disability-inclusive public health planning. We highlight person-centered approaches grounded in legal and human rights principles that provide access to brain health care and community-based supports. Finally, we discuss how tailored public health messaging and evidence-based workforce strategies can advance national and state brain health and dementia plans and improve equity in care for individuals with IDD. This paper illustrates how integrating disability-inclusive practices within public health systems can promote inclusive aging, improve dementia-related outcomes, and guide gerontologists in building inclusive, life course-oriented models of care.},
}

@article {pmid41032252,
year = {2025},
author = {Gaugler, JE and Johnson, E and Epstein-Lubow, G and Parker, L and Epps, F and Millenbah, A},
title = {Building a Public Health Infrastructure to Support Family Caregivers of People with Dementia.},
journal = {The Gerontologist},
volume = {},
number = {},
pages = {},
doi = {10.1093/geront/gnaf223},
pmid = {41032252},
issn = {1758-5341},
abstract = {The Centers for Disease Control and Prevention-funded Building Our Largest Dementia (BOLD) Infrastructure's Public Health Center of Excellence on Dementia Caregiving (PHCOE-DC) is one of three national centers designed to help public health departments strengthen and grow their Alzheimer's disease and related dementia initiatives. The PHCOE-DC specializes in disseminating tools and resources to help public health agencies develop programming and partnerships that support family caregivers of individuals with dementia. Through its reach and dissemination efforts, the PHCOE-DC has helped to elevate dementia caregiving as a priority for public health departments. Since 2020, the PHCOE-DC has increased visibility for the role of public health in strengthening the support infrastructure for family caregivers of individuals with dementia and has established a network of national leaders in dementia caregiving. This article summarizes PHCOE-DC's past work and potential future activities as the Center continues to elevate dementia caregiving as a priority for public health.},
}

@article {pmid41032250,
year = {2025},
author = {Chodosh, J and Borson, S and Nordyke, A and Kwon, SC and Marsh, K and Vedvyas, A and Lee, M},
title = {Advancing Early and Equitable Detection of Dementia: Key Learnings/Challenges, Recent Innovations, and Future Directions.},
journal = {The Gerontologist},
volume = {},
number = {},
pages = {},
doi = {10.1093/geront/gnaf221},
pmid = {41032250},
issn = {1758-5341},
abstract = {Worldwide, over half of all individuals with dementia are undiagnosed. In the United States, racial, ethnic, and economic inequities mirror global findings, with higher rates of missed and delayed diagnosis and poorer diagnostic quality among minoritized and disadvantaged groups. For example, delayed diagnosis is more prevalent among people identifying as non-Hispanic Black or Latino than non-Hispanic white. Systematic efforts to improve detection can increase diagnosis rates; there is broad consensus that earlier detection and initiation of focused care and support services benefit both affected individuals and their loved ones. Systemic under-detection and its contributions to persistent population-level suffering underscore the importance of early detection of dementia as a key public health issue. Improving early detection calls for comprehensive, coordinated responses from local, regional, and national public health systems in partnership with health care delivery systems and community-based organizations. The Public Health Center of Excellence on Early Detection of Dementia (PHCOE on EDD), funded by the Centers for Disease Control and Prevention (CDC), is a national resource to promote understanding and implementation of evidence-based and evidence-informed public health strategy for early detection of dementia. We, together with the PHCOEs on Dementia Risk Reduction and Dementia Caregiving, and nearly four dozen state and local initiatives, seek to operationalize the priorities of the Building Our Largest Dementia Infrastructure for Alzheimer's Act and National Healthy Brain Initiative, established by federal legislation in 2018 and 2024. Our efforts support the CDC's mandate to build a national public health infrastructure for brain health and dementia.},
}

@article {pmid41032245,
year = {2025},
author = {Roberts, SS and Lewis, M and Colcombe, CW and Kline, C and Donnelly, JM and Denno, B and Snyder, HM and Baumgart, M},
title = {Promoting Risk Reduction: Increasing Public Health Capacity to Address Dementia.},
journal = {The Gerontologist},
volume = {},
number = {},
pages = {},
doi = {10.1093/geront/gnaf227},
pmid = {41032245},
issn = {1758-5341},
abstract = {The Alzheimer's Association Building Our Largest Dementia (BOLD) Public Health Center of Excellence on Dementia Risk Reduction (Center), established in 2020, was created to assist public health agencies translate this science into action and build health department capacity to address dementia risk reduction. Through partnerships with the academic community and public health agencies, the Center provides tools, training, and data to support the integration of dementia risk reduction into existing chronic disease prevention and healthy aging efforts. This article outlines the Center's approach, highlights key initiatives and outcomes, and identifies opportunities for future research to strengthen public health infrastructure to reduce dementia risk across the lifespan. Despite the strong evidence, dementia risk reduction remains underutilized in public health practice. By equipping the workforce with accessible training and resources and fostering collaboration across sectors, the Center creates a bi-directional bridge between research, public health practice and implementation.},
}

@article {pmid41032155,
year = {2025},
author = {Gao, X and Yang, K and Yuan, X and Song, M and Wang, T and Shen, C},
title = {Research progress of exosomes used in the Alzheimer's disease treatment.},
journal = {Discover nano},
volume = {20},
number = {1},
pages = {173},
pmid = {41032155},
issn = {2731-9229},
support = {82402735//National Natural Science Foundation of China/ ; 2023NSFSC1481//Natural Science Foundation of Sichuan Province/ ; 2023HXBH122//Postdoctoral Research Foundation of West China Hospital of Sichuan University/ ; },
abstract = {Alzheimer's disease (AD) is a common form of dementia characterized by memory loss, cognitive and linguistic abilities declining and self-care capabilities diminishment. With the aging population globally, AD poses a significant threat to public health. Current treatments for AD aim to alleviate symptoms and slow down disease progression, but due to the limited understanding of underlying disease mechanisms, AD is still impossible to be cured yet. In recent years, there has been an exponential growth in exosome-related research because of their excellent biocompatibility ability, loading capacity and cellular internalization, making exosome to be one of the hotspots and a promising strategy in AD therapy research. This comprehensive review systematically explores the potential roles of various exosome-based nanotherapeutic strategy in AD treatment, with a particular focus on their specific biological mechanisms of action. Firstly, we elaborated on the pathological mechanisms of AD formation as well as the mechanisms related to the formation, secretion and function of exosome. Additionally, we highlighted the research progress in the development of exosome-based nanotherapeutic strategies for AD treatment and their corresponding biological mechanisms. Furthermore, we delved into the challenges and opportunities these strategies facing in clinical application. Looking forward to future research directions and trends, our review aims to provide a more comprehensive understanding and guidance with the application of exosome in AD treatment. Exosome-based nanotherapeutic strategies, as a new therapeutic approach, have opened up new possibilities for the treatment of AD and brought new light to patients.},
}

@article {pmid41032140,
year = {2025},
author = {Qahtan, SA and Al-Hussainy, AF and Arora, V and Rekha, MM and Kundlas, M and Chennakesavulu, K and Manu, M and Rizaev, J and Taher, SG and Alwan, M and Jawad, M and Mushtaq, H},
title = {Higher Serum Aspartate May be Associated with Better Cognitive Function as Mediated by Reduced Aβ Accumulation in Frontal and Temporal Lobes in Mild Cognitive Impairment.},
journal = {Journal of molecular neuroscience : MN},
volume = {75},
number = {4},
pages = {130},
pmid = {41032140},
issn = {1559-1166},
mesh = {Humans ; *Cognitive Dysfunction/blood/metabolism/genetics ; Male ; Female ; *Aspartic Acid/blood ; Aged ; *Amyloid beta-Peptides/metabolism ; *Temporal Lobe/metabolism ; *Alzheimer Disease/blood/metabolism/genetics ; *Frontal Lobe/metabolism ; Aged, 80 and over ; *Cognition ; Apolipoproteins E/genetics ; Middle Aged ; },
abstract = {Aspartate, a key excitatory neurotransmitter, has shown conflicting links to cognitive disorders like Alzheimer's disease (AD) and mild cognitive impairment (MCI). Given its role in brain function, studying its relationship with amyloid-beta (Aβ) accumulation may provide important insights into these conditions. This study is the first to examine the link between serum aspartate levels, Aβ accumulation in key brain regions, and cognitive function (via ADAS-Cog) across cognitively normal (n = 113), MCI (n = 283), and AD (n = 24) participants. The results showed significant increases in Aβ accumulation across all brain regions from CN to MCI and AD groups (overall p < 0.001; pairwise p ≤ 0.001). In individuals with MCI, elevated aspartate levels were inversely associated with Aβ accumulation in the frontal (β = - 0.122, p = 0.041) and temporal regions (β = - 0.128, p = 0.032), but this relationship was lost after adjusting for age, gender, education, handedness, and ApoE ɛ4, ɛ3, and ɛ2 genotypes. Further analysis identified age and ApoE ɛ4, ɛ3 status as key modifiers of the aspartate-Aβ relationship in MCI. Mediation analysis revealed that higher serum aspartate levels were associated with better cognitive function, potentially mediated by reduced Aβ accumulation in the frontal (β = - 0.037) and temporal lobes (β = - 0.043) in MCI, but this effect disappeared after adjusting for demographic factors and ApoE genotypes. Overall, higher serum aspartate levels may be associated with reduced Aβ accumulation and improved cognitive outcomes in MCI, with age and ApoE genotypes acting as key confounders.},
}

Humans
*Cognitive Dysfunction/blood/metabolism/genetics
Male
Female
*Aspartic Acid/blood
Aged
*Amyloid beta-Peptides/metabolism
*Temporal Lobe/metabolism
*Alzheimer Disease/blood/metabolism/genetics
*Frontal Lobe/metabolism
Aged, 80 and over
*Cognition
Apolipoproteins E/genetics
Middle Aged

@article {pmid41032131,
year = {2025},
author = {Mazzeo, S and Boveri, S and Bortolin, E and Bruschi, G and Girani, E and Bombaci, A and Pozzi, FE and Corbari, MV and Ambrogi, F and Agosta, F and Filippi, M and Salsone, M and , },
title = {Data-driven subtypes of subjective cognitive decline: neuropsychological profiles, Alzheimer's disease biomarkers, and clinical trajectories.},
journal = {Journal of neurology},
volume = {272},
number = {10},
pages = {669},
pmid = {41032131},
issn = {1432-1459},
support = {2024 Robert Katzman Award//American Academy of Neurology/ ; },
mesh = {Humans ; Male ; Female ; *Cognitive Dysfunction/classification/cerebrospinal fluid/diagnostic imaging/psychology/physiopathology ; *Alzheimer Disease/cerebrospinal fluid/diagnostic imaging/psychology/classification/physiopathology ; Aged ; Biomarkers/cerebrospinal fluid ; Positron-Emission Tomography ; Neuropsychological Tests ; Aged, 80 and over ; Magnetic Resonance Imaging ; Disease Progression ; Amyloid beta-Peptides/cerebrospinal fluid ; tau Proteins/cerebrospinal fluid ; Middle Aged ; Follow-Up Studies ; },
abstract = {OBJECTIVES: Subjective Cognitive Decline (SCD) is a heterogeneous condition recognized as the earliest manifestation of Alzheimer's disease (AD). We hypothesized that the heterogeneity of SCD may be synthesized in distinct subtypes.

METHODS: We analyzed data from the AD Neuroimaging Initiative (ADNI) database. For all participants, demographic variables, cognitive measures, APOE genotype, CSF biomarkers, brain MRI, and FDG-PET data were available. Participants underwent follow-up visits every 6 or 12 months.

RESULTS: 542 cognitively normal (CN), 346 SCD, and 423 early mild cognitive impairment (E-MCI) individuals were included. A data-driven approach based on cognitive measures identified three SCD clusters (k1, k2, k3) that performed differently in verbal memory (k2 outperformed all the groups and k3 showed the poorest performance, p < 0.001) and in executive function (k1 had the lowest scores, p = 0.006). Regarding CSF biomarkers, k2 exhibited lower p-tau (20.6 ± 9.2 vs. 24.2 ± 13.6, p = 0.03) and k3 had higher Aβ42 levels (1131.3 ± 379.8 vs. 942.87 ± 355.3, p = 0.01) compared to the E-MCI group, while there were no differences between k1 and E-MCI. Regarding brain FDG-PET, k1 demonstrated reduced uptake compared to CN, k2, and k3 (p < 0.001). During follow-up, k1 exhibited a higher rate of progression to MCI or dementia compared to k2 and k3 (Log-rank χ[2] = 18.18, p = 0.0002) and a steeper decline in general cognition and long-term verbal memory compared to k2.

INTERPRETATION: We proposed a three-subgroup system classification for SCD, reflecting different cognitive profiles and longitudinal trajectories. Classifying individuals with SCD may enhance diagnostic pathways and inform personalized interventions.},
}

Humans
Male
Female
*Cognitive Dysfunction/classification/cerebrospinal fluid/diagnostic imaging/psychology/physiopathology
*Alzheimer Disease/cerebrospinal fluid/diagnostic imaging/psychology/classification/physiopathology
Aged
Biomarkers/cerebrospinal fluid
Positron-Emission Tomography
Neuropsychological Tests
Aged, 80 and over
Magnetic Resonance Imaging
Disease Progression
Amyloid beta-Peptides/cerebrospinal fluid
tau Proteins/cerebrospinal fluid
Middle Aged
Follow-Up Studies

@article {pmid41032100,
year = {2025},
author = {Yu, L and Feng, M and Shang, Y and Ren, Z and Xing, H and Chang, Y and Dong, K and Xiao, Y and Qin, Y and Dai, H},
title = {The relationship between choroid plexus volume, DTI-ALPS index, kidney function, and amyloid pathology in alzheimer's disease.},
journal = {Neuroradiology},
volume = {},
number = {},
pages = {},
pmid = {41032100},
issn = {1432-1920},
support = {81971573//National Natural Science Foundation of China/ ; GSWS2020019//Suzhou Gusu Medical Youth Talent/ ; },
abstract = {PURPOSE: To explore the effect of the choroid plexus volume (CPV) changes on paravascular drainage function, Alzheimer's disease (AD) pathology, and the kidney-brain axis in AD.

METHODS: A total of 74 AD patients and 32 healthy controls (HC) were included for this study, and cerebrospinal fluid (CSF) AD biomarker data and serum creatinine levels were collected from 28 AD patients. CP volume (CPV) calculation was performed using 3D-T1 images and the diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) index was calculated using DTI images to assess paravascular drainage function. Mediation analyses were used to assess the mediating role of CPV and ALPS index between kidney function and AD pathology.

RESULTS: AD patients had larger CPV and smaller ALPS index than HCs (p < 0.001), and both were associated with cognitive performance in the overall cohort(B = -4.7, SEM, 1.478, p = 0.002; B = 3.8, SEM, 1.789, p = 0.037) and could serve as independent predictors for AD (p < 0.01). In AD patients with CSF data, CPV was negatively associated with estimated glomerular filtration rate (eGFR) (r = -0.402; p = 0.046), CSF amyloid-β (Aβ) 40 (r = -0.415; p = 0.039) and positively associated with Aβ42/Aβ40 ratio (r = 0.505; p = 0.01). CPV partially mediated the effect of kidney function on AD pathology while ALPS index did not.

CONCLUSION: CPV and ALPS index may serve as potential imaging markers for AD, and the CP was involved in the crosstalk of the kidney-brain axis.},
}

@article {pmid41032080,
year = {2025},
author = {Khatun, P and Li, X and Xiaoxi, Z and Zhai, J and Ullah, A and Bo, Y and Lyu, Q},
title = {Effect of Omega-3 Polyunsaturated Fatty Acid Supplements on Cognitive Performance in Patients with Mild Cognitive Impairment or Alzheimer's Disease: A Systematic Review and Meta-Analysis.},
journal = {Nutrition reviews},
volume = {},
number = {},
pages = {},
doi = {10.1093/nutrit/nuaf167},
pmid = {41032080},
issn = {1753-4887},
support = {YJ20220181//2022 International Postdoctoral Exchange Fellowship Program/ ; 232102310069//Henan Medical Science and Technology Research Program/ ; //Preferential support for scientific research of overseas persons in Henan Province/ ; },
abstract = {CONTEXT: A positive effect of omega-3 polyunsaturated fatty acids (n-3 PUFAs) on brain activity has been observed within subjects who have Alzheimer's disease (AD) or mild cognitive impairment (MCI). However, inconsistent findings have been reported regarding the efficacy or ineffectiveness of an n-3 PUFA dietary intervention for cognitive improvement.

OBJECTIVE: To address this problem, our thorough investigation and statistical analysis sought to assess the impact of n-3 PUFA dietary intake on cognitive function among persons diagnosed with AD or MCI.

DATA SOURCES: The databases consulted included PubMed, PubMed Central Library, and the Cochrane Library.

DATA EXTRACTION: Nine articles reporting on the findings of randomized controlled trials that looked at the link between n-3 PUFA intake and cognitive performance-related outcomes were included in the comprehensive evaluation, with the meta-analysis utilizing 7 of these. Key details such as author, publication year, study area, research type, pathology (MCI or AD), were incorporated into the data extraction procedure.

DATA ANALYSIS: Evaluation of the included studies used Cochrane risk-of-bias instruments, a random-effects model, standardized mean differences (SMDs) and 95% CIs.

RESULTS: Our findings have provided evidence of the effectiveness of an n-3 PUFA treatment in improving Full-Scale IQ (FSIQ) (SMD -0.82; 95% CI: -1.57, -0.08; P = .000), information processing (SMD -2.90; 95% CI: -5.25, -0.56; P = .000), and digit span/working memory/attention aspects of cognitive functioning (SMD -1.89; 95% CI: -3.27, -0.51; P = .000). No evidence was found for the effectiveness of an n-3 PUFA treatment in improving image completion (SMD -0.07; 95% CI: -0.50, 0.35; P = .000), picture layout (SMD -0.08; 95% CI: -0.32, 0.16; P = .075), block design SMD -0.15; 95% CI: -0.37, 0.03; P = .123), or arithmetic aspects of cognitive functioning (SMD -0.33; 95% CI: -0.61, 0.04; P = .007).

CONCLUSION: In summary, n-3 PUFAs have been found to significantly affect some domains of cognitive function, such as FSIQ, information processing, and digit span/working memory/attention in subjects with MCI. However, no significant effect was observed for some domains, such as picture completion, picture arrangement, or block design.},
}

@article {pmid41032078,
year = {2025},
author = {Wei, H and Hu, J and Haider, A and Wei, J and Ma, J and Lu, H and Li, Y and Jiang, Y and Yi, H and Gong, H and Tan, Z and Gong, J and Guo, B and Zheng, X and Xu, H and Wang, H and Wang, L},
title = {Quantitative analysis of [[18]F]CHL2310, a novel PET ligand for cholesterol 24-Hydroxylase, in nonhuman primate brain.},
journal = {European journal of nuclear medicine and molecular imaging},
volume = {},
number = {},
pages = {},
pmid = {41032078},
issn = {1619-7089},
support = {82371998//National Natural Science Foundation of China/ ; 82402345//National Natural Science Foundation of China/ ; 202206010106//Guangzhou Science and Technology Program of China/ ; 2024A03J1042//Guangzhou Science and Technology Program of China/ ; 2024A03J0828//Guangzhou Science and Technology Program of China/ ; 2023B1212060062//Open Program at Guangdong Provincial Key Laboratory of Research on Emergency in TCM/ ; 18DZ2260400//Shanghai Key Laboratory of Molecular Imaging/ ; },
abstract = {PURPOSE: Cholesterol 24-hydroxylase (CYP46A1) is a brain-specific enzyme catalyzes the conversion of cholesterol into 24S-hydroxycholesterol, thereby playing a pivotal role in maintaining cerebral cholesterol homeostasis. Dysregulation of this pathway has been implicated in various neurological disorders, including Alzheimer's disease, Huntington's disease, epilepsy, and depression. To enable quantitative assessment of CYP46A1 activity in vivo, a CYP46A1-targeted PET radiotracer with high specificity and favorable pharmacokinetics is envisioned. This study aimed to evaluate the metabolic stability, target specificity, and pharmacokinetic properties of [[18]F]CHL2310, a novel CYP46A1 PET radioligand, in non-human primates.

METHODS: [[18]F]CHL2310 was synthesized using a tosylate precursor. Baseline and TAK-935 pre-blocked PET imaging with arterial blood sampling were performed in non-human primates. Whole-blood and plasma radioactivity, plasma free fraction, and metabolite analysis were conducted to generate metabolite-corrected plasma input functions. Regional brain time-activity curves were fitted using one-tissue compartment model, two-tissue compartment model and Logan graphical analysis to estimate total distribution volume. CYP46A1 occupancy by TAK-935 was quantified using Lassen plots, enabling the assessment of the dose-occupancy relationship. Non-displaceable binding potential was calculated using either non-displaceable distribution volume or the cerebellum as a reference region. Test-retest variability was evaluated in baseline scans from the same subject. Additionally, whole-body PET imaging was performed in male and female monkeys to estimate human radiation dosimetry.

RESULTS: [[18]F]CHL2310 was synthesized with a non-decay-corrected radiochemical yield of 6.7 ± 1.5% and radiochemical purity >99%. The tracer demonstrated high specific binding in NHP brain with reasonable metabolic stability and a free fraction of 13.1 ± 0.8% in plasma. TACs were well described by two-tissue compartment model and Logan graphical analysis. TAK-935 exhibited dose-dependent CYP46A1 occupancy with a half-maximal inhibitory dose of 0.0095 mg/kg, derived from Lassen plots. The averaged test-retest variability of tissue distribution volumes was -3.0 ± 4.8%, and the averaged absolute TRV was 4.4 ± 3.5%. The effective radiation dose for humans was estimated as 0.013 mSv/MBq.

CONCLUSION: [[18]F]CHL2310 shows high in vivo specificity, favorable pharmacokinetic properties, and robust quantitative performance in non-human primates. These characteristics support its potential as a PET radiotracer for imaging CYP46A1 in human studies.},
}

@article {pmid41032076,
year = {2025},
author = {Lin, HC and Huang, KL and Chen, SH and Ho, TY and Huang, CC and Hsu, JL and Chang, CC and Lin, KJ and Hsiao, IT},
title = {Visual interpretation of [[18]F]Florzolotau Tau-PET imaging for differentiating alzheimer's disease and progressive supranuclear palsy.},
journal = {European journal of nuclear medicine and molecular imaging},
volume = {},
number = {},
pages = {},
pmid = {41032076},
issn = {1619-7089},
support = {CORPG3P0281, CORPG3P0291, CMRPG3K1093, CORPG3P0021, CORPG3N0011//Chang Gung Memorial Hospital/ ; CMRPD1N0401, BMRP488//Chang Gung Memorial Hospital/ ; NSTC 113-2314-B-182-042-MY2//National Science and Technology Council/ ; },
abstract = {INTRODUCTION: Tau accumulation in the brain is a hallmark of both Alzheimer's disease (AD) and progressive supranuclear palsy (PSP), complicating differential diagnosis. The novel [[18]F]Florzolotau tauPET enables invivo detection. This study tests a visual reading approach on [[18]F]Florzolotau PET for reliably separating AD from PSP and assessing its clinical usefulness.

METHODS: Eightynine participants of Aβpositive AD, Aβnegative PSP, and cognitively unimpaired controls (CU) underwent [[18]F]​Florzolotau PET, [[18]F]​Florbetapir amyloidPET, and MRI. Visual interpretation of the tau-PET scans was performed using a colormap-based method, dividing the brain into AD-specific regions and PSP-specific regions. Regional tau uptake was scored visually, and the results were compared with SUVr values from quantitative analysis. Decision tree analysis was used to classify patients based on visual scores.

RESULTS: The study found significant differences in visual scores between the CU, AD, and PSP groups, particularly in the AD-specific and PSP-specific regions. Visual assessment of tau uptake moderately correlated with SUVr values, especially in AD-specific regions. The decision tree model using visual scores accurately classified CU, AD, and PSP patients, with sensitivity and specificity rates exceeding 85%. Interobserver agreement for visual scoring was high, supporting the reliability of this method in clinical settings.

CONCLUSION: Visual interpretation scoring system of [[18]F] Florzolotau tau-PET reliably distinguishes AD from PSP, shows strong correlations with diagnoses, and is simpler than quantitative analyses for routine practice. Larger cohorts must confirm accuracy, refine the method, and assess its ability to grade disease severity.},
}

@article {pmid41031951,
year = {2025},
author = {Nasrallah, I},
title = {Let's Agree to Be Wrong: Transforming Alzheimer Disease Diagnosis.},
journal = {Radiology. Artificial intelligence},
volume = {7},
number = {6},
pages = {e250686},
doi = {10.1148/ryai.250686},
pmid = {41031951},
issn = {2638-6100},
}

@article {pmid41031881,
year = {2025},
author = {Wisch, JK and Ances, BM},
title = {Ruling in, ruling out: the clinical utility of plasma biomarkers in diagnosis of Alzheimer's disease.},
journal = {The Journal of clinical investigation},
volume = {135},
number = {19},
pages = {},
doi = {10.1172/JCI198725},
pmid = {41031881},
issn = {1558-8238},
}

@article {pmid41031684,
year = {2025},
author = {Tong, K and Wainwright, JE and Horne, J and Jones, K and Dadova, K and Alder, E and Leu, A and Birkett-Swan, L and Vseteckova, J},
title = {Navigating dementia care: a systematic review of young and young adult carers' needs and support solutions.},
journal = {Aging & mental health},
volume = {},
number = {},
pages = {1-14},
doi = {10.1080/13607863.2025.2564719},
pmid = {41031684},
issn = {1364-6915},
abstract = {OBJECTIVES: This systematic review aimed to explore the available support and identify the unique needs of young and young adult carers of individuals with dementia.

METHOD: A systematic review following PRISMA guidelines was conducted. Electronic databases, including PubMed, Web of Science, PsycINFO, CINAHL, and Ovid, along with Google Scholar for grey literature, were searched. A narrative synthesis approach was used to analyse the findings of the included studies. The quality of the articles was assessed using the Mixed Methods Appraisal Tool (MMAT).

RESULTS: Seven studies met the predefined inclusion criteria and were included in the narrative synthesis. Findings revealed that young and young adult carers often lack knowledge of available support services and face challenges navigating the healthcare system. Caregiving responsibilities were found to hinder educational and career aspirations, leading to social isolation and strained relationships. The support received from family, friends, and teachers was often inconsistent and inadequate. A significant finding was the lack of differentiation between young and young adult carers in the existing research, despite their distinct social care support needs.

CONCLUSION: The limited research highlights a critical gap in the literature regarding the support and needs of young and young adult carers of people with dementia. The lack of distinction between these two groups, who receive different social care support, emphasises the need for further research to better understand their unique experiences. There is an urgent need for targeted education and support programmes that address the distinct developmental needs and challenges of this population, promoting their well-being and safeguarding their personal and educational aspirations.},
}

@article {pmid41031602,
year = {2025},
author = {Premathilaka, MB and Hansmann, UHE},
title = {Modulation of Aβ1-42 Aggregation by a SARS-CoV-2 Protein Fragment.},
journal = {Journal of chemical information and modeling},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.jcim.5c01811},
pmid = {41031602},
issn = {1549-960X},
abstract = {A number of studies have pointed out the possibility that SARS-CoV-2 infections could trigger amyloid diseases such as Parkinson's disease or type II diabetes. In the present study, we probe this question for Alzheimer's disease, which is connected with the presence of amyloids rich in Aβ peptides. For this purpose, we study, by way of molecular dynamics simulations, the interaction between the fragment FKNIDGYFKI of the Spike protein with an Aβ1-42 monomer and two fibril models, one patient-derived and one synthetic. We find that the viral protein fragment appears to shift the ensemble of monomer conformations toward more aggregation-prone ones, and that fibril polymorphs found in patients with Alzheimer's disease appear to be more stabilized than synthetic fibrils. We discuss commonalities and differences in the modulation of amyloid formation by the viral protein fragments by comparing our results with previous studies of other amyloid-forming proteins.},
}

@article {pmid41031399,
year = {2025},
author = {Yang, AJT and Mohammad, A and Crozier, RWE and Maddalena, L and Tsiani, E and MacNeil, AJ and Spencer, GE and Necakov, A and Duarte-Guterman, P and Stuart, J and MacPherson, REK},
title = {Differences in inflammatory markers, mitochondrial function, and synaptic proteins in male and female Alzheimer's disease post mortem brains.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21},
number = {10},
pages = {e70645},
doi = {10.1002/alz.70645},
pmid = {41031399},
issn = {1552-5279},
support = {//NSERC Canada Graduate Studies/ ; //Canada Foundation for Innovation and the Ontario Research Fund to MacNeil/ ; NWI- 191320/CAPMC/CIHR/Canada ; //ORF and CFI/ ; },
mesh = {Humans ; *Alzheimer Disease/metabolism/pathology ; Female ; Male ; *Mitochondria/metabolism ; *Brain/metabolism/pathology ; Aged ; Biomarkers/metabolism ; Aged, 80 and over ; *Inflammation/metabolism/pathology ; *Synapses/metabolism ; Sex Factors ; Autopsy ; Cytokines/metabolism ; Sex Characteristics ; },
abstract = {INTRODUCTION: Inflammation and mitochondrial impairments are suggested to underlie Alzheimer's disease (AD) development. This study examined whether metabolic, synaptic, and inflammatory markers in AD differed from non-demented brains.

METHODS: Male and female AD brains were analyzed by immunofluorescence, Western blot, enzyme-linked immunosorbent assay-based cytokine, and mitochondrial respiration analysis.

RESULTS: AD brains had greater Akt phosphorylation, but only AD males had greater downstream mammalian target of rapamycin phosphorylation. AD females showed lower mitochondrial complex IV respiration. AD brains had greater expression of synaptic markers α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, glutamate receptor 1, and synaptophysin, while AD females had a higher expression ELKS1. Microglial expression was lower in AD gray matter, AD females had higher microglial expression in white matter, while cytokine interleukin 2 content was greater in AD brains.

DISCUSSION: Markers of impaired insulin signaling, impaired mitochondrial function, and greater neuroinflammation were found in AD brains. Female brains had greater differences in metabolic signaling than males and this dysregulation is unique/worse with AD.

HIGHLIGHTS: Neuroinflammation and metabolic function are worse with Alzheimer's disease (AD). Female brains exhibit more distinct changes in metabolic signaling than males. Female brains have worse metabolic changes with AD. Harmful inflammatory and mitochondrial signaling may promote AD.},
}

Humans
*Alzheimer Disease/metabolism/pathology
Female
Male
*Mitochondria/metabolism
*Brain/metabolism/pathology
Aged
Biomarkers/metabolism
Aged, 80 and over
*Inflammation/metabolism/pathology
*Synapses/metabolism
Sex Factors
Autopsy
Cytokines/metabolism
Sex Characteristics

@article {pmid41031381,
year = {2025},
author = {O'Hanlon, CE and Schutz, S},
title = {Assessing Cumulative, Meaningful Benefits of Disease-Modifying Therapies Targeting Synucleinopathies: Conference Proceedings and Roadmap for Research.},
journal = {Rand health quarterly},
volume = {12},
number = {4},
pages = {1},
pmid = {41031381},
issn = {2162-8254},
abstract = {This article summarizes the Workshop on Assessing Cumulative Benefits of Disease-Modifying Therapies (DMTs) Targeting Synucleinopathies, which was held in New York, N.Y., on November 18 and 19, 2024. This event was hosted by a coalition of nonprofit organizations and brought together representatives from academia, industry, and patient advocacy communities to discuss the cumulative, meaningful benefits of DMTs for synucleinopathies; to identify priorities for the field; and to explore opportunities for collaboration. Synucleinopathies, including Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy, are neurodegenerative conditions that share underlying pathobiology and have many clinical similarities, including difficulties with movement, changes in cognition, sleep disturbances, and autonomic symptoms. Although there are some available symptomatic treatments for synucleinopathies, DMTs-medications that address the underlying biological processes of illness-are currently under development and might obtain regulatory approval in the near future. However, many other factors contribute to whether patients will have access to these novel therapies. Governments, private payers, clinicians, medical professional specialty societies, patients, and care partners think about meaningful benefits differently from regulators, who focus on safety and efficacy. The workshop attendees discussed these factors and considered next steps for understanding the benefits of DMTs for synucleinopathies.},
}

@article {pmid41031197,
year = {2025},
author = {Wang, Q and Wang, DL and Zhang, XC and Jiang, XY and Jiang, HN and Yang, XY and Zhang, T and Lv, YY and Li, Q},
title = {Efficacy and safety of traditional Chinese medicine and Western medicine in Alzheimer's disease: a systematic review and meta-analysis.},
journal = {Frontiers in neurology},
volume = {16},
number = {},
pages = {1607945},
pmid = {41031197},
issn = {1664-2295},
abstract = {OBJECTIVE: This study aimed to compare the efficacy and safety of traditional Chinese medicine (TCM) compounds with single Western medicines in treating Alzheimer's disease (AD) through a systematic review and meta-analysis.

METHODS: In this study, we searched for randomized controlled trials on the treatment of AD with TCM compounds published before March 2025 in Chinese and English databases (PubMed, Embase, Cochrane, China National Knowledge Infrastructure, VIP, and Wanfang) and conducted a meta-analysis using Stata15.0 software.

RESULTS: A total of 23 studies were included, involving 2,035 participants (1,173 in the experimental group and 862 in the control group). Traditional Chinese herbal compounds showed good clinical efficacy and maintenance effects in the treatment of AD. The effective rate of TCM compounds in treating AD was higher than that of Western medicine (relative risk ratio = 1.19, 95% CI: 1.04-1.37, p = 0.009). In terms of the Alzheimer's Disease Assessment Scale-Cognitive and Hierarchic Dementia Scale-Revised scores, TCM compounds were superior to Western medicine (standardized mean difference = -0.22, 95% CI: -0.40--0.05). There were no significant differences between the two groups in the Mini-Mental State Examination or Activities of Daily Living scores. Additionally, there were no significant differences in adverse reactions between the TCM compounds and Western medicine groups.

CONCLUSION: The present research indicates that TCM compounds could be a promising therapeutic option for AD, demonstrating encouraging results in terms of efficacy and safety, particularly regarding certain cognitive functions.},
}

@article {pmid41031163,
year = {2025},
author = {Kareem, AI and Kapp, E and Joubert, J and Zou, X},
title = {Dual GSK3β/SIRT1 modulators for Alzheimer's: mechanisms, drug discovery and future perspectives.},
journal = {Frontiers in pharmacology},
volume = {16},
number = {},
pages = {1662241},
pmid = {41031163},
issn = {1663-9812},
abstract = {Alzheimer's disease (AD) remains without effective disease-modifying therapies, in part due to the limited efficacy of single-target approaches. Dual modulation of glycogen synthase kinase-3β (GSK3β), a key driver of tau hyperphosphorylation and amyloid-β (Aβ) production, and sirtuin-1 (SIRT1), a neuroprotective NAD[+]-dependent deacetylase, has emerged as a promising therapeutic strategy. This review explores the mechanistic rationale for concurrently inhibiting GSK3β and activating SIRT1 to disrupt AD's pathological cascade while enhancing endogenous neuroprotective pathways. Natural compounds such as resveratrol, berberine, pterostilbene, and quercetin exhibit this dual activity and provide scaffolds for rational drug design. However, challenges related to target selectivity, blood-brain barrier penetration, and clinical translation persist. Advances in multi-target drug discovery, including pharmacophore hybridization, structure-based modelling, cheminformatics, nanoformulation and delivery strategies offer new avenues to overcome these hurdles. A dual GSK3β/SIRT1-targeting strategy exemplifies a systems-level approach to restoring neurophysiological balance and holds potential to achieve more effective, disease-modifying outcomes in AD.},
}

@article {pmid41030967,
year = {2025},
author = {Da Silva, IIN and Ramirez, D and Parylak, SL and Wallace, LA and Tucker, JK and Erberich, JM and Katariya, R and McDonald, AH and Gallina, IS and Tucker, AL and Burgado, J and Jaeger, BN and Barron, JJ and Pratt, JM and Pena, M and Racha, V and Lim, CK and Fernandes, S and Benassi, S and Randolph-Moore, L and Vadodaria, KC and Marchetto, MC and Allen, NJ and Gage, FH},
title = {CK2 inhibition suppresses glial inflammation in the brain.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.08.05.668554},
pmid = {41030967},
issn = {2692-8205},
abstract = {Neuroinflammation plays a key role in Alzheimer's disease (AD) and related neurodegenerative disorders. Chronic activation of astrocytes and microglia fuels neuronal damage via cytokine secretion, oxidative stress, and proteolysis. However, glial inflammatory regulation remains poorly understood. Using chemoproteomics, we identified CK2, particularly the brain-enriched catalytic subunit CK2α2, as a key driver of astrocytic inflammation. CK2 enhances NF-κB activity by phosphorylating NF-κB S529 and IκBα S32, promoting pro-inflammatory gene expression. CK2 inhibition via genetic or chemical approaches dampens inflammation, including IL-6 and IL-8 expression in an acute neuroinflammation mouse model. CK2α2 is upregulated in AD postmortem tissues and patient-derived astrocytes. AD astrocytes exhibit a hyperinflammatory state that can be attenuated by CK2 inhibition. Overexpression of CK2α2 in cortical organoids mimics AD pathology, whereas CK2 inhibition using the potent, selective, and brain-penetrant probe TAL606 rescues inflammatory markers in transgenic AD mice. These findings position CK2 as a central regulator of neuroinflammation and a promising therapeutic target for AD and related disorders.},
}

@article {pmid41030887,
year = {2025},
author = {Pan, Q and Lu, J and Xiao, Z and Zhang, H and Liu, G and Li, Y},
title = {Construction of a Rat Model of Hemilateral Parkinson's Disease Induced by Human Wild-Type α-Synuclein Overexpression.},
journal = {Neuropsychiatric disease and treatment},
volume = {21},
number = {},
pages = {2183-2194},
pmid = {41030887},
issn = {1176-6328},
abstract = {OBJECTIVE: Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder after Alzheimer's disease. The precise etiology and pathogenesis of PD remain unclear. Human wild-type α-synuclein has been implicated in PD pathogenesis. The objective of this study is to examine the role of α-synuclein in PD by establishing a rat model of substantia nigra degeneration and Motor behavioral changes through the induced overexpression of human α-synuclein.

METHODS: Rats were randomly assigned to either the Negative control group or the adeno-associated virus serotype 9 (AAV9) treatment group. Animals in the AAV9 group received 2.5 μL of AAV9 expressing human wild-type α-synuclein, while those in the Negative control group received an equal volume of AAV9 expressing green fluorescent protein via stereotactic unilateral injection into the substantia nigra pars compacta. Behavioral assessments were conducted at 1-, 3-, and 8-weeks following virus administration. Tyrosine hydroxylase and human α-synuclein expression in the substantia nigra pars compacta were analyzed. Additionally, dopamine, dihydroxyphenylacetic acid, and homovanillic acid levels in the striatum were quantified.

RESULTS: After 3 weeks of virus induction, neurodegeneration of the right substantia nigra was observed, with a reduction in the number of tyrosine hydroxylase-immunopositive neurons in the AAV9 group. By 8 weeks, substantia nigra neurodegeneration had further progressed, and animals in the AAV9 group exhibited apomorphine-induced asymmetrical rotation and altered forelimb use.

CONCLUSION: Overexpression of human wild-type α-synuclein led to substantia nigra degeneration and Motor behavioral changes in rats, providing a viable model for exploring the pathogenesis of Parkinson's disease. Limitations include the 8-week observation window and the absence of neuroinflammation markers.},
}

@article {pmid41030378,
year = {2025},
author = {Gazes, Y and Suzuki, H and Morris, LA and Lee, S and Jin, Z and Huey, ED and Chen, BB and Le Heron, C and Heibronner, SR and Vanegas-Arroyave, N},
title = {A transdiagnostic, multi-modal approach to understanding apathy: Methodological and analytical framework.},
journal = {Neuroimage. Reports},
volume = {5},
number = {4},
pages = {100289},
pmid = {41030378},
issn = {2666-9560},
abstract = {Apathy is characterized by loss of motivation and manifests as a reduction of goal-directed behavior. Apathy is highly prevalent across neurodegenerative diseases, including Alzheimer's Disease (AD) and Parkinson's Disease (PD), and is an important contributor to the disability and reduce quality of life in these conditions. The treatment of apathy remains challenging due to a lack of specific therapies, largely attributed to an incomplete understanding of its cognitive and neuroanatomical underpinnings, crucial for developing targeted interventions. Apathy can be mechanistically studied through effort-based decision-making (EBDM) paradigms, where individuals choose between low- and high-effort tasks for varying reward magnitudes. Anatomically, apathy has been associated with alterations in brain regions previously implicated in EBDM. Using a novel transdiagnostic study design in individuals with AD and PD, we aim to: (1) evaluate the independent effects of reward and effort sensitivity as a mechanistic link between apathy and neurodegeneration of basal ganglia-frontal networks and, (2) in a subset of PD patients receiving deep brain stimulation (DBS) surgery, determine whether electrical manipulation of subthalamic nucleus and/or DBS connectivity, directly alter reward and effort information processing and, consequently, goal-directed behavior. Understanding how neurodegeneration-alone or in combination with neuromodulatory interventions-drives apathy, is essential for guiding clinical decision-making and therapeutic development. Given its prevalence across neurodegenerative disorders, apathy provides a unique framework for investigating shared and disease-specific neuroanatomical, functional, and behavioral mechanisms. In this protocol paper, we describe the rationale and methodology of our proposed multimodal approach, to investigate apathy in a transdiagnostic cohort of individuals with AD and PD.},
}

@article {pmid41030285,
year = {2025},
author = {},
title = {Correction to "Macromolecular nanoparticles to attenuate both reactive oxygen species and inflammatory damage for treating Alzheimer's disease".},
journal = {Bioengineering & translational medicine},
volume = {10},
number = {5},
pages = {e70052},
doi = {10.1002/btm2.70052},
pmid = {41030285},
issn = {2380-6761},
abstract = {[This corrects the article DOI: 10.1002/btm2.10459.].},
}

@article {pmid41030243,
year = {2025},
author = {Ambikairajah, A and Foxe, D and de Lange, AG and Carrick, J and Cheung, SC and Srikanth, VK and Hwang, YT and Ahmed, RM and Burrell, JR and Piguet, O},
title = {A Bayesian analysis of diagnostic timelines across Alzheimer's disease, frontotemporal dementia, and other neurodegenerative conditions.},
journal = {Alzheimer's & dementia (Amsterdam, Netherlands)},
volume = {17},
number = {3},
pages = {e70184},
pmid = {41030243},
issn = {2352-8729},
abstract = {INTRODUCTION: Timely diagnosis is crucial for managing neurodegenerative conditions. This study investigated whether time from symptom onset to diagnosis differs by clinical syndrome and sex.

METHODS: This retrospective, cross-sectional study included 591 participants with Alzheimer's disease (AD), frontotemporal dementia (FTD) subtypes (behavioral variant FTD [bvFTD], semantic dementia [SD], and progressive non-fluent aphasia), logopenic progressive aphasia (LPA), and syndromes associated with movement disorders (corticobasal syndrome, FTD with motor neuron disease [FTD-MND], and progressive supranuclear palsy). Bayesian regression models were used to compute diagnostic timelines.

RESULTS: Compared to AD (3.35 years; 95% credible interval [CrI]: 3.03-3.72), SD and bvFTD had additional delays of 9.7 (95% CrI: 1.96-20.64) and 14.82 months (95% CrI: 6.94-25.42), respectively, while FTD-MND was shorter by 11.62 months (95% CrI: -15.7 to -4.68). Men with bvFTD had 23.64 month longer delays than women (95% CrI: 10.35-44.33).

DISCUSSION: Diagnostic delays may reflect syndrome-specific clinical features, diagnostic complexity, and sociocultural factors. Findings highlight the need for improved diagnostic pathways and pre-clinical biomarkers to facilitate earlier identification.

HIGHLIGHTS: Bayesian analyses revealed that diagnostic delays differ by syndrome and sex.Alzheimer's disease (AD) was diagnosed on average 3.35 years after symptom onset.Diagnoses were delayed in semantic and behavioral variant frontotemporal dementia (bvFTD) compared to AD.Men with bvFTD had longer delays than women.Findings support need for improved diagnostic pathways and pre-clinical biomarkers.},
}

@article {pmid41030130,
year = {2025},
author = {Markova, TZ and Fonseca, CS and Ciampa, CJ and Murphy, A and Landau, S and Harrison, TM and Berry, AS and , },
title = {Defining the contributions of tau pathology in the amygdala to increasing depressive symptoms in aging.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21},
number = {10},
pages = {e70740},
doi = {10.1002/alz.70740},
pmid = {41030130},
issn = {1552-5279},
support = {U19AG024904//NIA/NIH/ ; AG034570//NIA/NIH/ ; AG062542//NIA/NIH/ ; AG081759//NIA/NIH/ ; AG087628//NIA/NIH/ ; },
mesh = {Humans ; *Amygdala/metabolism/diagnostic imaging/pathology ; Male ; Female ; *tau Proteins/metabolism ; Aged ; *Aging/metabolism/pathology/psychology ; *Depression/diagnostic imaging/metabolism/pathology/genetics ; Positron-Emission Tomography ; Longitudinal Studies ; Cross-Sectional Studies ; Apolipoprotein E4/genetics ; Aged, 80 and over ; Amyloid beta-Peptides/metabolism ; Alzheimer Disease ; Carbolines ; },
abstract = {BACKGROUND: Amygdala tau accumulates in cognitively normal individuals and may contribute to neuropsychiatric changes.

METHODS: Using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), we investigated relationships among cross-sectional and longitudinal tau ([18F]Flortaucipir [FTP] positron emission tomography), changes in depressive symptoms and memory, and amyloid beta and apolipoprotein E (APOE) ε4 status. We report secondary analyses from the Berkeley Aging Cohort Study (BACS).

RESULTS: Longitudinal increases in depressive symptoms were associated with higher baseline FTP and increasing FTP in the amygdala. Relationships between FTP and depressive symptoms were strongest in APOE ε4 carriers, with moderation effects replicating in BACS. Entorhinal FTP did not show associations with depressive symptoms beyond variance explained by the amygdala but showed some specific associations with memory decline.

DISCUSSION: Our findings indicate the strongest coupling between tau accumulation and depressive symptoms in APOE ε4 carriers and reinforce the importance of amygdala tau in understanding neuropsychiatric changes in older adults.

HIGHLIGHTS: There is a lack of research focused on the role of tau in the amygdala in cognitively normal older adults. Amygdala tau is related to both worsening depressive symptoms and declining memory performance. APOE ε4 carriers seem to drive positive tau-depressive symptom associations. Focusing on the amygdala tau is useful for understanding neuropsychiatric trajectories in cognitively unimpaired older adults.},
}

Humans
*Amygdala/metabolism/diagnostic imaging/pathology
Male
Female
*tau Proteins/metabolism
Aged
*Aging/metabolism/pathology/psychology
*Depression/diagnostic imaging/metabolism/pathology/genetics
Positron-Emission Tomography
Longitudinal Studies
Cross-Sectional Studies
Apolipoprotein E4/genetics
Aged, 80 and over
Amyloid beta-Peptides/metabolism
Alzheimer Disease
Carbolines

@article {pmid41030129,
year = {2025},
author = {Soleimani-Meigooni, DN and Pezzoli, S and Blazhenets, G and La Joie, R and Lin, Z and Soppe, CL and Johnson, DR and Koran, MEI and McConathy, JE and Nasrallah, IM and Ponisio, MR and Tanner, JA and Villemagne, VL and Windon, CC and Zeineh, M and Biber, S and Kukull, WA and O'Connell, H and Peterson, DJ and Mormino, EC and Johnson, SC and Rabinovici, GD and , and , and , },
title = {Calibration of multisite raters for prospective visual reads of amyloid PET scans.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21},
number = {10},
pages = {e70732},
doi = {10.1002/alz.70732},
pmid = {41030129},
issn = {1552-5279},
support = {U19 AG024904/AG/NIA NIH HHS/United States ; R56/U01 AG057195/AG/NIA NIH HHS/United States ; //Northern California Institute for Research and Education/ ; //National Institute of Biomedical Imaging and Bioengineering, the Canadian Institutes of Health Research/ ; U01 AG082350/AG/NIA NIH HHS/United States ; U24 AG072122/AG/NIA NIH HHS/United States ; //Brain Canada Foundation/ ; },
mesh = {Humans ; *Positron-Emission Tomography/methods ; *Alzheimer Disease/diagnostic imaging ; Calibration ; Observer Variation ; Reproducibility of Results ; *Amyloid/metabolism ; *Brain/diagnostic imaging/metabolism ; },
abstract = {INTRODUCTION: In multicenter Alzheimer's disease studies, amyloid positron emission tomography (PET) visual reads are typically performed centrally by a few experts. Incorporating a broader reader network enhances scalability and generalizability.

METHODS: Ten neuroimaging experts from eight Alzheimer's Disease Research Centers (ADRCs) visually read 180 amyloid PET scans (30 scans and 15 duplicate scans for each of four tracers, imaged across a wide variety of scanners), using preferred reading software without anatomical imaging or quantitation. Scans were classified as elevated or non-elevated per tracer-specific criteria. Inter- and intra-rater agreement was assessed.

RESULTS: Inter-rater agreement was substantial (Fleiss' κ = 0.78), with full consensus on 69% of scans. Inter-rater reliability was substantial to perfect across tracers (Fleiss' κ = 0.70-0.87). Intra-rater agreement was substantial to perfect (Cohen's κ = 0.79-1). Scans with intermediate (10-40 Centiloid) quantitation had lower reader agreement.

DISCUSSION: A multicenter expert network achieved substantial agreement classifying amyloid PET scans. These scans provide a standard for reader training and reliability assurance in future studies.

HIGHLIGHTS: Calibration methods ensure reliable amyloid positron emission tomography (PET) visual reads across multiple raters. Substantial agreement is possible across readers using their preferred tools. Agreement is also substantial regardless of the amyloid PET tracer used. Scans with intermediate (10-40 Centiloid) quantitation have lower reader agreement. The calibration set will become a training tool for amyloid PET visual read studies.},
}

Humans
*Positron-Emission Tomography/methods
*Alzheimer Disease/diagnostic imaging
Calibration
Observer Variation
Reproducibility of Results
*Amyloid/metabolism
*Brain/diagnostic imaging/metabolism

@article {pmid41030116,
year = {2025},
author = {Awodiya, E},
title = {The Eye as a Window to Brain Health: Can Retinal Imaging and AI Modeling Predict Alzheimer's Disease?.},
journal = {Brain and behavior},
volume = {15},
number = {10},
pages = {e70890},
doi = {10.1002/brb3.70890},
pmid = {41030116},
issn = {2162-3279},
mesh = {Humans ; *Alzheimer Disease/diagnosis/diagnostic imaging/physiopathology ; *Retina/diagnostic imaging ; Early Diagnosis ; *Brain ; Cognitive Dysfunction ; Biomarkers ; },
abstract = {OBJECTIVE: This is a review article to evaluate clinical evidence for the vascular model of Alzheimer's disease (AD) pathology and elucidate the extent to which retinal imaging with AI modeling can be useful in earlier diagnosis of the condition.

METHODS: I comprehensively reviewed the literature on the current understanding of AD pathology and emerging role of the neurovascular system. I reviewed the evidence for retinal vascular biomarkers that can predict the presence of cognitive impairments seen in AD and AI models that utilize these to diagnose and elucidate pathophysiology for the condition.

RESULTS: It is found that retinal imaging offers a non-invasive and cost-effective way to detect AD-related neurovascular changes and, when coupled with AI, holds a transformative role in improving screening, diagnostics, and our understanding of the disease.

CONCLUSION: There is evidence to suggest that retinal imaging can provide an earlier diagnosis of the condition. This can change the practice by encouraging lifestyle modification as crucial in modifying the progression of the disease.},
}

Humans
*Alzheimer Disease/diagnosis/diagnostic imaging/physiopathology
*Retina/diagnostic imaging
Early Diagnosis
*Brain
Cognitive Dysfunction
Biomarkers

@article {pmid41030020,
year = {2025},
author = {Parums, DV},
title = {Editorial: Real-World Outcomes of Disease-Modifying Therapies Highlight the Need for Diagnostic Biomarkers in Early Alzheimer's Disease.},
journal = {Medical science monitor : international medical journal of experimental and clinical research},
volume = {31},
number = {},
pages = {e951655},
doi = {10.12659/MSM.951655},
pmid = {41030020},
issn = {1643-3750},
mesh = {Humans ; *Alzheimer Disease/diagnosis/blood/drug therapy/therapy ; *Biomarkers/blood ; tau Proteins/blood ; Amyloid beta-Peptides/blood ; Positron-Emission Tomography/methods ; },
abstract = {The promise of targeted humanized monoclonal antibody therapies to amyloid ß and tau protein in Alzheimer's disease from clinical trial data has not been realized when put to the test in real-world studies and practice. There have been regulatory approvals for diagnostic blood tests in China, Japan (HISCL Aß42/40), and the United Kingdom (UK) (PrecivityAD2). On May 16, 2025, the US FDA approved the Lumipulse G blood test, which utilizes the plasma pTau217/Aß1-42 ratio, for the diagnosis of cerebral amyloid plaques in symptomatic patients of 55 years or more. Biological biomarkers and targets are currently being evaluated in phase 1 to phase 3 clinical trials, to rapidly implement less invasive blood-based assays to detect tau species and neurofilament light (NfL). However, clinical validation of the diagnostic value of identifying blood biomarkers still requires support from amyloid positron emission tomography (PET) brain scans and/or the results of cerebrospinal fluid (CSF) analysis. This editorial aims to identify how real-world outcomes of new disease-modifying therapies highlight the need for diagnostic biomarkers for early Alzheimer's disease and the current status of biomarkers identified by blood plasma, CSF, and imaging.},
}

Humans
*Alzheimer Disease/diagnosis/blood/drug therapy/therapy
*Biomarkers/blood
tau Proteins/blood
Amyloid beta-Peptides/blood
Positron-Emission Tomography/methods

@article {pmid41030017,
year = {2025},
author = {Bieberich, E},
title = {Ceramide Links Alzheimer's Disease to Decreased Cancer Risk: A Lipid Behind the Enigma of Inverse Comorbidity.},
journal = {Cancer research},
volume = {85},
number = {19},
pages = {3579-3581},
doi = {10.1158/0008-5472.CAN-25-2288},
pmid = {41030017},
issn = {1538-7445},
mesh = {*Alzheimer Disease/metabolism/epidemiology ; Humans ; *Ceramides/metabolism ; *Neoplasms/metabolism/epidemiology ; Mitochondria/metabolism ; Animals ; Comorbidity ; Amyloid beta-Peptides/metabolism ; },
abstract = {For decades, epidemiologic studies have consistently reported an inverse comorbidity between Alzheimer's disease (AD) and cancer: Individuals with AD are less likely to develop cancer and vice versa. The biological basis of this paradox has remained largely unresolved. A study by Kassir and colleagues in this issue of Cancer Research provides a compelling mechanistic insight into this paradox by demonstrating that amyloid precursor protein and its cleavage product Aβ40, known for their pathologic accumulation in the AD brain, also accumulate in peripheral T cells where they suppress mitochondrial ceramide production and lethal autophagy. This preservation of mitochondrial function enhances the antitumor immunity of T cells. Previous work has established that ceramide can promote neurodegeneration in the brain. The suppression of ceramide generation by amyloid precursor protein and Aβ40 in the periphery, thereby preserving mitochondrial integrity and supporting anticancer immunity, further establishes ceramide as a context-dependent regulator of cell fate and a key factor in the inverse AD-cancer relationship. See related article by Kassir et al., p. 3791.},
}

*Alzheimer Disease/metabolism/epidemiology
Humans
*Ceramides/metabolism
*Neoplasms/metabolism/epidemiology
Mitochondria/metabolism
Animals
Comorbidity
Amyloid beta-Peptides/metabolism

@article {pmid41029924,
year = {2025},
author = {Prabhu, AD and Tiwari, P and Dubey, S},
title = {Neuroprotective Potential of Butrin: Mechanistic and Therapeutic Insights.},
journal = {Current drug research reviews},
volume = {},
number = {},
pages = {},
doi = {10.2174/0125899775398736250911114640},
pmid = {41029924},
issn = {2589-9783},
abstract = {INTRODUCTION: Butrin, a flavonoid glycoside derived from Butea monosperma, has garnered attention for its neuroprotective effects attributed to its multifaceted pharmacological profile. It modulates dopamine and norepinephrine levels and exhibits antioxidant, antiinflammatory, and mitochondrial-protective actions. These properties position butrin as a promising candidate for therapeutic intervention in neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease. This review consolidates mechanistic insights, preclinical evidence, and therapeutic perspectives of butrin to assess its potential clinical applicability in managing neurodegenerative disorders.

METHODS: This review critically analyzes existing preclinical studies on the neuroprotective effects of butrin. Emphasis is placed on its mechanisms of action, including mitigation of oxidative stress, suppression of neuroinflammation, enhancement of neurotrophic factors, and preservation of mitochondrial integrity. Additionally, the review explores current limitations in clinical translation and evaluates emerging drug delivery strategies aimed at improving its therapeutic potential.

RESULTS: Preclinical evidence indicates that butrin effectively counters excitotoxicity and protein aggregation, key pathological features of neurodegenerative disorders. It attenuates neuropathological processes and demonstrates synergistic effects when combined with other neuroprotective and anti-inflammatory agents. Nonetheless, its poor bioavailability and limited ability to cross the blood-brain barrier remain significant barriers to clinical application.

DISCUSSION: Despite its promising pharmacological profile, the clinical translation of butrin is constrained by absorption challenges and suboptimal pharmacokinetics. Innovative strategies, such as nanocarrier-based delivery systems, drug repurposing, and combination therapies, may enhance its therapeutic efficacy. Addressing these limitations is crucial for advancing butrin from bench to bedside.

CONCLUSION: Butrin exhibits compelling neuroprotective properties supported by robust preclinical data. However, large-scale clinical trials are essential to validate its efficacy. Integrating advanced drug delivery systems and personalized medicine approaches may unlock its full potential in managing neurodegenerative diseases.},
}

@article {pmid41029918,
year = {2025},
author = {Agarwal, M and Singhal, M and Basist, P and Tamta, N and Kumar, S and Saha, S},
title = {Evaluation of Hordenine's Therapeutic Potential in Alzheimer's Disease-Induced Cognitive and Oxidative Impairments.},
journal = {Recent advances in food, nutrition & agriculture},
volume = {},
number = {},
pages = {},
doi = {10.2174/012772574X389943250908070348},
pmid = {41029918},
issn = {2772-5758},
abstract = {INTRODUCTION: This research aimed to investigate the potential of Hordenine (HR) against Alzheimer's Disease (AD) induced by Streptozotocin (STZ) in Wistar rats by evaluating its impact on cognitive function, oxidative stress, inflammatory cytokines, and neuroprotective biomarkers in comparison to donepezil.

METHODS: The study involved five groups of Wistar rats: a control group, a group with STZinduced AD, and three treatment groups receiving varying doses of HR (50 mg/kg and 75 mg/kg) and donepezil (5 mg/kg). Over 28 days, the animals underwent various behavioural tests to assess cognitive function, along with biochemical analyses to measure A+cetylcholinesterase (AChE) activity, oxidative stress markers, inflammatory cytokines (IL-1β, TNF-α), and nuclear factor kappa B (NF-κB) levels, and histological examination. Additionally, molecular docking studies were performed to assess the interaction of HR with AChE.

RESULTS: STZ administration caused significant cognitive decline, oxidative stress, and elevated inflammatory markers. HR supplementation, particularly at 75 mg/kg, significantly improved cognition, reduced oxidative stress, and decreased pro-inflammatory cytokines (IL-1β, TNF-α), as well as NF-κB levels, while increasing Brain-Derived Neurotrophic Factor (BDNF) expression. Molecular docking studies revealed strong binding of HR to AChE, suggesting potential inhibitory effects.

DISCUSSION: Hordenine demonstrated promising neuroprotective effects against STZ-induced neurotoxicity by improving cognition and reducing oxidative stress and inflammation, suggesting HR's potential as an adjunct therapy for Alzheimer's disease, offering a protective mechanism that may complement existing treatments like donepezil.

CONCLUSION: The research shows that the medicinal plant HR exhibits neuroprotective potential against AD induced by STZ. Further research involving clinical trials is warranted to fully establish the efficacy and safety of HR in the treatment of AD.},
}

@article {pmid41029886,
year = {2025},
author = {Fan, X and Wang, H and Guo, C and Huang, S and Xia, L and Zhou, Z and Tao, R and Li, M and Wang, X and Qian, W},
title = {IRF1 ameliorates synaptic dysfunction through the modulation of O-GlcNAcylation on GluN1 subunit of NMDAR.},
journal = {Alzheimer's research & therapy},
volume = {17},
number = {1},
pages = {205},
pmid = {41029886},
issn = {1758-9193},
support = {JC2023042//the project of Nantong Natural Science Foundation/ ; 81872875//National Natural Science Foundation of China/ ; },
mesh = {Animals ; *Receptors, N-Methyl-D-Aspartate/metabolism ; *Interferon Regulatory Factor-1/metabolism/genetics ; Mice ; *Alzheimer Disease/metabolism/genetics ; Mice, Transgenic ; Hippocampus/metabolism/pathology ; Humans ; *Synapses/metabolism/pathology ; Neuronal Plasticity/physiology ; Male ; Disease Models, Animal ; Mice, Inbred C57BL ; },
abstract = {BACKGROUND: Synaptic dysfunction, which occurs before the formation of amyloid plaques (Aβ) and neurofibrillary tangles (NFTs), is strongly associated with cognitive deficits and represents major early clinical features of Alzheimer's disease (AD). Abnormal NMDAR signaling emerges as a noticeable feature of synaptic dysfunctions in AD. Nonetheless, the underlying mechanisms of NMDAR dysfunctions remain unclear.

METHODS: 3xTg-AD mice were injected with AAV-IRF1. Cognitive function was assessed using behavioral tests, while biochemical and immunofluorescence analyses were conducted to evaluate the protein levels of IRF-1, OGA, subunits of NMDAR, O-GlcNAcylation of NMDAR subunits, and internalization of NMDA receptors. Synaptic alterations in the hippocampus were detected by electrophysiology and Golgi staining.

RESULTS: In the present study, we demonstrate that Interferon Regulatory Factor-1 (IRF-1), which is deficient in the brain of individuals with Alzheimer's disease (AD), negatively regulates the O-GlcNAcylation levels of GluN1 through transcriptional regulation of the human OGA gene. Furthermore, IRF-1 may influence trafficking of NMDARs, thereby affecting dendritic spine density and synaptic plasticity, and ultimately improving the learning and memory of 3xTg-AD mice.

CONCLUSION: Our results indicate that IRF1 can improve the cognitive function of 3xTg-AD mice by regulating the O-GlcNAcylation of GluN1, offering evidence that IRF-1 could serve as a novel therapeutic target for treating synaptic dysfunction in Alzheimer's diseases.},
}

Animals
*Receptors, N-Methyl-D-Aspartate/metabolism
*Interferon Regulatory Factor-1/metabolism/genetics
Mice
*Alzheimer Disease/metabolism/genetics
Mice, Transgenic
Hippocampus/metabolism/pathology
Humans
*Synapses/metabolism/pathology
Neuronal Plasticity/physiology
Male
Disease Models, Animal
Mice, Inbred C57BL

@article {pmid41029885,
year = {2025},
author = {Zhou, J and Zhong, Y and Jin, C and Dong, L and Zhou, R and Wang, Y and Fan, Z and Zheng, X and Xing, X and Wang, J and Tian, M and Zhang, H},
title = {A novel electric field approach for improving cognitive function through ameliorating cell-specific pathology in P301S tauopathy mice.},
journal = {Alzheimer's research & therapy},
volume = {17},
number = {1},
pages = {210},
pmid = {41029885},
issn = {1758-9193},
support = {82394433//National Natural Science Foundation of China/ ; 82030049//National Natural Science Foundation of China/ ; 2022YFE0118000//National Key Research and Development Program of China/ ; 226-2024-00059//Fundamental Research Funds for the Central Universities/ ; },
mesh = {Animals ; *Tauopathies/pathology/therapy/genetics ; Mice ; Mice, Transgenic ; Disease Models, Animal ; Microglia/pathology/metabolism ; *Cognition/physiology ; Brain/pathology/metabolism ; Neurons/pathology/metabolism ; tau Proteins/genetics/metabolism ; *Cognitive Dysfunction/therapy/pathology ; Male ; Mice, Inbred C57BL ; Oxidative Stress/physiology ; *Electric Stimulation Therapy/methods ; },
abstract = {Alzheimer's disease (AD) is a devastating neurodegenerative disorder, with no effective treatment currently available. Recently, non-pharmacological therapy, especially gamma frequency stimulation has shown promising therapeutic effects in Alzheimer's disease (AD) mouse models. Electric field (EF) is a non-invasive biophysical approach for neuronal protection. However, whether EF is beneficial in AD neuropathology remains unknown. In this study, we exposed the P301S tauopathy mouse model to EF at gamma frequency on the head. We demonstrated that EF treatment significantly improved the cognitive impairments in the P301S mice. This was accompanied by reduced tau pathologies, suppressed microglial activation, neuroinflammation and oxidative stress in the tauopathy mouse brain. Moreover, EF treatment induced cell-specific responses in neural cells, with neurons being more susceptible, followed by microglia and oligodendrocytes. EF also had favorable effects on synaptic protein in neurons, inflammatory response and complement signaling in microglia, and myelination in oligodendrocytes. This study provides strong evidence that EF at gamma frequency may have great potential to be a novel therapeutic intervention for P301S by attenuating neuropathology and offering neuroprotection.},
}

Animals
*Tauopathies/pathology/therapy/genetics
Mice
Mice, Transgenic
Disease Models, Animal
Microglia/pathology/metabolism
*Cognition/physiology
Brain/pathology/metabolism
Neurons/pathology/metabolism
tau Proteins/genetics/metabolism
*Cognitive Dysfunction/therapy/pathology
Male
Mice, Inbred C57BL
Oxidative Stress/physiology
*Electric Stimulation Therapy/methods

@article {pmid41029842,
year = {2025},
author = {Gorski, D and Evans, H and Allison, T and Barria, C and Harrison, D and Banerjee, V and Mendez, N and Shahnawaz, M and Kaalund, S and Folke, J and Aznar, S and Schultz, P and Wang, F and Soto, C},
title = {Design and application of a Tau seed amplification assay for screening inhibitors of Tau seeding.},
journal = {Alzheimer's research & therapy},
volume = {17},
number = {1},
pages = {214},
pmid = {41029842},
issn = {1758-9193},
mesh = {*tau Proteins/metabolism/antagonists & inhibitors ; Humans ; *Alzheimer Disease/metabolism/pathology ; *Brain/metabolism/pathology/drug effects ; Drug Evaluation, Preclinical/methods ; *Protein Aggregation, Pathological/metabolism ; Protein Aggregates/drug effects ; },
abstract = {BACKGROUND: Tau protein aggregates are a key pathological hallmark of Alzheimer's disease (AD) and are closely associated with cognitive decline and neurodegeneration. It is proposed that tau aggregates faithfully propagate throughout the brain by self-templating their disease-associated conformation onto natively-folded tau monomers, thereby inducing their aggregation and incorporation into growing fibrils. As such, the inhibition or modulation of tau seeding and aggregation represents a viable therapeutic strategy for AD and other tauopathies.

METHODS: We have recently developed seed amplification assays (SAA) for the detection and amplification of small quantities of misfolded protein aggregates in various neurodegenerative diseases. In this article, we adapted the SAA technology to amplify the process of tau aggregation and seeding in AD brain samples. Using the Tau-SAA we screened two chemical libraries: one comprising over 20 suspected aggregation inhibitors and the other comprising over 200 FDA-approved, blood-brain barrier-permeable compounds from a commercial chemical library. We also performed secondary in vitro assays to confirm the activity of selected hits as well as determining the IC50 of the most active compounds.

RESULTS: Our Tau-SAA detects the presence of tau seeds even after a 100-million-fold dilution of the initial inoculum. Examination of 26 postmortem brain samples from AD and control cases confirmed that our assay is specific for AD brain tau seeds. Screening of 220 compounds showed that approximately 57% of suspected aggregation inhibitors and ~ 3% of CNS-penetrant compounds inhibited over 75% of AD brain-templated tau aggregation.

CONCLUSIONS: In conclusion, our data suggests that Tau-SAA readily detects the presence of tau seeds in AD brains but not in controls, and that by amplifying AD brain tau seeds, the assay may serve as a valuable primary drug screening platform.},
}

*tau Proteins/metabolism/antagonists & inhibitors
Humans
*Alzheimer Disease/metabolism/pathology
*Brain/metabolism/pathology/drug effects
Drug Evaluation, Preclinical/methods
*Protein Aggregation, Pathological/metabolism
Protein Aggregates/drug effects

@article {pmid41029837,
year = {2025},
author = {Cabrera, C and Carrión, N and Mateo, D and Vicens, P and Pinzón, A and Heredia, L and Forcadell-Ferreres, E and Pino, M and Yerga, B and Zaragoza, J and Vicente-Pascual, M and Moral, A and Arco, T and Arjó, M and Martínez, E and Galvez, S and Lozano, MJ and Torrente, M},
title = {Gut microbiota characterization in ageing, mild cognitive impairment, and Alzheimer's disease in the context of mediterranean lifestyle in a Spanish population.},
journal = {Alzheimer's research & therapy},
volume = {17},
number = {1},
pages = {211},
pmid = {41029837},
issn = {1758-9193},
support = {PID2019-103888RB-I00//Ministerio de Ciencia e Innovación/ ; PID2019-103888RB-I00//Agencia Estatal de Investigación/ ; },
}

@article {pmid41029835,
year = {2025},
author = {Henderson, SK and Halai, A and Tsvetanov, KA and Cope, TE and Patterson, KE and Rowe, JB and Lambon Ralph, MA},
title = {Disentangling phonology from phonological short-term memory in Alzheimer's disease phenotypes.},
journal = {Alzheimer's research & therapy},
volume = {17},
number = {1},
pages = {206},
pmid = {41029835},
issn = {1758-9193},
support = {OPP1144//Gates Cambridge Trust/ ; (MC_UU_00030/14; MR/P01271X/1; MR/T033371/1)/MRC_/Medical Research Council/United Kingdom ; (MC_UU_00030/14; MR/P01271X/1; MR/T033371/1)/MRC_/Medical Research Council/United Kingdom ; (MC_UU_00030/14; MR/P01271X/1; MR/T033371/1)/MRC_/Medical Research Council/United Kingdom ; (MC_UU_00030/14; MR/P01271X/1; MR/T033371/1)/MRC_/Medical Research Council/United Kingdom ; (MC_UU_00030/14; MR/P01271X/1; MR/T033371/1)/MRC_/Medical Research Council/United Kingdom ; 602/ALZS_/Alzheimer's Society/United Kingdom ; BRC-1215-20014; NIHR203312//NIHR Cambridge Biomedical Research Centre/ ; BRC-1215-20014; NIHR203312//NIHR Cambridge Biomedical Research Centre/ ; BRC-1215-20014; NIHR203312//NIHR Cambridge Biomedical Research Centre/ ; 220258/WT_/Wellcome Trust/United Kingdom ; },
mesh = {Humans ; *Memory, Short-Term/physiology ; Male ; Female ; *Alzheimer Disease/complications/diagnostic imaging/psychology/physiopathology ; Aged ; *Phonetics ; Neuropsychological Tests ; Phenotype ; *Aphasia, Primary Progressive/diagnostic imaging/physiopathology/psychology ; Middle Aged ; Magnetic Resonance Imaging ; Aged, 80 and over ; Bayes Theorem ; },
abstract = {BACKGROUND: Impaired phonological short-term memory is a core feature of the logopenic variant of primary progressive aphasia (lvPPA), but it is not clear whether a core phonological processing deficit is also present.

METHODS: We asked three questions: (i) beyond short-term memory impairment, do lvPPA patients have an impairment within phonology itself?; (ii) is their performance in working memory and naming reflective of this phonological impairment?; and (iii) is their repetition performance related to structural and functional differences in key language-dominant regions? We compared non-word and word repetition and short-term memory performance in patients with typical Alzheimer's disease (tAD), lvPPA per consensus criteria, and others who previously satisfied definitions of lvPPA but had progressed with multi-domain cognitive impairments (lvPPA+).

RESULTS: Bayesian analyses revealed no group differences in phonological tasks of word and non-word repetition. We found very strong evidence for an effect of self-reported hearing loss on word and non-word repetition, but not multi-syllabic word/phrase repetition. A comparison of phonological versus working memory and naming tasks produced either no evidence or evidence for no correlation. Beyond the expected grey matter reductions in patients relative to controls, there was anecdotal evidence for an association between non-word repetition and functional connectivity between dorsal premotor and posterior superior temporal gyrus regions in patients.

CONCLUSIONS: Our results indicated that, in the absence of self-reported hearing loss, patients did not exhibit impairments in tasks tapping "pure" phonological processing. Our results suggest that instead of having a core phonological impairment, lvPPA patients have a working memory/buffering impairment.},
}

Humans
*Memory, Short-Term/physiology
Male
Female
*Alzheimer Disease/complications/diagnostic imaging/psychology/physiopathology
Aged
*Phonetics
Neuropsychological Tests
Phenotype
*Aphasia, Primary Progressive/diagnostic imaging/physiopathology/psychology
Middle Aged
Magnetic Resonance Imaging
Aged, 80 and over
Bayes Theorem

@article {pmid41029783,
year = {2025},
author = {Yoon, YJ and Seo, S and Lee, S and Lim, H and Choo, K and Kim, D and Han, H and So, M and Kang, H and Kang, S and Kim, D and Lee, YG and Shin, D and Jeon, TJ and Yun, M},
title = {Centiloid values from deep learning-based CT parcellation: a valid alternative to freesurfer.},
journal = {Alzheimer's research & therapy},
volume = {17},
number = {1},
pages = {212},
pmid = {41029783},
issn = {1758-9193},
mesh = {Humans ; *Deep Learning ; Male ; Female ; Aged ; *Alzheimer Disease/diagnostic imaging/metabolism ; *Positron Emission Tomography Computed Tomography/methods ; Magnetic Resonance Imaging/methods ; Middle Aged ; Amyloid beta-Peptides/metabolism ; *Brain/diagnostic imaging/metabolism ; Adult ; Aged, 80 and over ; Image Processing, Computer-Assisted/methods ; Stilbenes ; Aniline Compounds ; },
abstract = {BACKGROUND: Amyloid PET/CT is essential for quantifying amyloid-beta (Aβ) deposition in Alzheimer's disease (AD), with the Centiloid (CL) scale standardizing measurements across imaging centers. However, MRI-based CL pipelines face challenges: high cost, contraindications, and patient burden. To address these challenges, we developed a deep learning-based CT parcellation pipeline calibrated to the standard CL scale using CT images from PET/CT scans and evaluated its performance relative to standard pipelines.

METHODS: A total of 306 participants (23 young controls [YCs] and 283 patients) underwent 18 F-florbetaben (FBB) PET/CT and MRI. Based on visual assessment, 207 patients were classified as Aβ-positive and 76 as Aβ-negative. PET images were processed using the CT parcellation pipeline and compared to FreeSurfer (FS) and standard pipelines. Agreement was assessed via regression analyses. Effect size, variance, and ROC analyses were used to compare pipelines and determine the optimal CL threshold relative to visual Aβ assessment.

RESULTS: The CT parcellation showed high concordance with the FS and provided reliable CL quantification (R² = 0.99). Both pipelines demonstrated similar variance in YCs and effect sizes between YCs and ADCI. ROC analyses confirmed comparable accuracy and similar CL thresholds, supporting CT parcellation as a viable MRI-free alternative.

CONCLUSIONS: Our findings indicate that the CT parcellation pipeline achieves a level of accuracy similar to FS in CL quantification, demonstrating its reliability as an MRI-free alternative. In PET/CT, CT and PET are acquired sequentially within the same session on a shared bed and headrest, which helps maintain consistent positioning and adequate spatial alignment, reducing registration errors and supporting more reliable and precise quantification.},
}

Humans
*Deep Learning
Male
Female
Aged
*Alzheimer Disease/diagnostic imaging/metabolism
*Positron Emission Tomography Computed Tomography/methods
Magnetic Resonance Imaging/methods
Middle Aged
Amyloid beta-Peptides/metabolism
*Brain/diagnostic imaging/metabolism
Adult
Aged, 80 and over
Image Processing, Computer-Assisted/methods
Stilbenes
Aniline Compounds

@article {pmid41029738,
year = {2025},
author = {Zhou, K and Zhang, J and Su, J and Tong, W and Li, R and Xiang, X and Jin, L and Song, Y},
title = {Exploration and validation of the immune-related genes signatures and potential molecular mechanisms shared between Alzheimer's disease (AD) and Parkinson's disease (PD).},
journal = {BMC medical genomics},
volume = {18},
number = {1},
pages = {141},
pmid = {41029738},
issn = {1755-8794},
support = {81901301//National Natural Science Foundation of China/ ; 82172545//National Natural Science Foundation of China/ ; HBRC2105//Ganquan Outstanding Youth Fund/ ; 2023ZZ02027//Shanghai Research Center of Rehabilitation Medicine(Top Priority Research Center of Shanghai)/ ; KYPT202202//Shanghai Yangzhi Rehabilitation Hospital/ ; 2024CRZD010//Sunshine Program for Clinical Research Incubation funded by Shanghai Yangzhi Rehabilitation Hospital/ ; },
}

@article {pmid41029733,
year = {2025},
author = {Coupé, P and Mansencal, B and Morandat, F and Morell-Ortega, S and Villain, N and Manjón, JV and Planche, V},
title = {petBrain: a new pipeline for amyloid, Tau tangles and neurodegeneration quantification using PET and MRI.},
journal = {Alzheimer's research & therapy},
volume = {17},
number = {1},
pages = {209},
pmid = {41029733},
issn = {1758-9193},
support = {ANR-23-CE45-0020-01//Agence Nationale de la Recherche/ ; 2022-AD011013848R1//GENCI/ ; PID2023-152127OB-I00//Ministerio de Ciencia, Innovacion y Universidades of Spain/ ; },
mesh = {Humans ; *Positron-Emission Tomography/methods ; *Magnetic Resonance Imaging/methods ; *tau Proteins/metabolism ; *Alzheimer Disease/diagnostic imaging/metabolism/pathology ; *Neurofibrillary Tangles/pathology/metabolism ; *Brain/diagnostic imaging/pathology/metabolism ; *Plaque, Amyloid/diagnostic imaging/pathology ; Male ; Female ; Aged ; Biomarkers ; },
abstract = {INTRODUCTION: Quantification of amyloid plaques (A), neurofibrillary tangles (T2), and neurodegeneration (N) using PET and MRI is critical for Alzheimer's disease (AD) diagnosis and prognosis. Existing pipelines face limitations regarding processing time, tracer variability handling, and multimodal integration.

METHODS: We developed petBrain, a novel end-to-end processing pipeline for amyloid-PET, tau-PET, and structural MRI. It leverages deep learning-based segmentation, standardized biomarker quantification (Centiloid, CenTauR, HAVAs), and simultaneous estimation of A, T2, and N biomarkers. It is implemented in a web-based format, requiring no local computational infrastructure and software usage knowledge.

RESULTS: petBrain provides reliable, rapid quantification with results comparable to existing pipelines for A and T2, showing strong concordance with data processed in ADNI databases. The staging and quantification of A/T2/N by petBrain demonstrated good agreements with CSF/plasma biomarkers, clinical status and cognitive performance.

DISCUSSION: petBrain represents a powerful open platform for standardized AD biomarker analysis, facilitating clinical research applications.},
}

Humans
*Positron-Emission Tomography/methods
*Magnetic Resonance Imaging/methods
*tau Proteins/metabolism
*Alzheimer Disease/diagnostic imaging/metabolism/pathology
*Neurofibrillary Tangles/pathology/metabolism
*Brain/diagnostic imaging/pathology/metabolism
*Plaque, Amyloid/diagnostic imaging/pathology
Male
Female
Aged
Biomarkers

@article {pmid41029594,
year = {2025},
author = {de Rijke, TJ and Visser, LNC and Kaijser, KKM and Bruinsma, J and Oudbier, SJ and Heger, I and van der Flier, WM and Smets, EMA and Engelsma, T},
title = {Intention to use and perceived satisfaction with a digital tool for dementia prevention among the Dutch general public: a cross-sectional study.},
journal = {BMC public health},
volume = {25},
number = {1},
pages = {3151},
pmid = {41029594},
issn = {1471-2458},
support = {#73305095007/ZONMW_/ZonMw/Netherlands ; #73305095007/ZONMW_/ZonMw/Netherlands ; #73305095007/ZONMW_/ZonMw/Netherlands ; #LSHM20106//Health~Holland/ ; #LSHM20106//Health~Holland/ ; #LSHM20106//Health~Holland/ ; 101017405//Horizon 2020/ ; 101017405//Horizon 2020/ ; 1051003210004//Ministerie van Volksgezondheid, Welzijn en Sport/ ; },
}

@article {pmid41029426,
year = {2025},
author = {Akande, A and Park, JE and Scott, R and Alexander, JS and Nam, HW},
title = {Neurogranin-MYH9 interaction regulates cytoskeletal remodeling in cerebral vasculature.},
journal = {Fluids and barriers of the CNS},
volume = {22},
number = {1},
pages = {94},
pmid = {41029426},
issn = {2045-8118},
support = {P20 GM134974/GF/NIH HHS/United States ; P20GM121307/GF/NIH HHS/United States ; },
mesh = {Animals ; *Neurogranin/metabolism/genetics ; *Myosin Heavy Chains/metabolism ; Mice ; *Endothelial Cells/metabolism ; *Cytoskeleton/metabolism ; Humans ; *Brain/metabolism/blood supply ; Mice, Knockout ; Blood-Brain Barrier/metabolism ; Mice, Inbred C57BL ; Signal Transduction/physiology ; },
abstract = {Neurogranin (Ng), a known regulator of neuronal Ca[2+]-calmodulin (CaM) signaling, is linked to Alzheimer's disease. Though well-studied in neurons, Ng is also expressed in brain vasculature, where its function remains unclear. To investigate Ng's role in brain microvascular endothelial cells, we defined its interactome using immunoprecipitation-mass spectrometry (IP-MS) under high- and low-Ca[2+] conditions. Among 119 Ng-binding proteins, we discovered a novel interaction between Ng and MYH9, a key regulator of cytoskeletal remodeling. Ng-MYH9 binding was prominent in high Ca[2+] and validated via CaM affinity pulldown and proximity ligation assays. Ng knockdown reduced F-actin levels, while MYH9 knockdown decreased both Ng and F-actin. Loss of Ng-MYH9 also impaired AKT-GSK3β signaling and elevated the endothelial activation marker VCAM1. Ng-null mice exhibited disrupted brain microvascular architecture and reduced MYH9 expression in endothelial cells. These findings reveal a novel Ng pathway promoting MYH9-dependent cytoskeletal remodeling and a potential role in maintaining blood-brain barrier integrity, a previously unrecognized function for Ng in brain health and Alzheimer's disease.},
}

Animals
*Neurogranin/metabolism/genetics
*Myosin Heavy Chains/metabolism
Mice
*Endothelial Cells/metabolism
*Cytoskeleton/metabolism
Humans
*Brain/metabolism/blood supply
Mice, Knockout
Blood-Brain Barrier/metabolism
Mice, Inbred C57BL
Signal Transduction/physiology

@article {pmid41029423,
year = {2025},
author = {Wei, T and Chang, J and Zhao, Y and Li, A and Sun, W and Liu, X and Liu, H and Xing, Y and Wang, Z and Tang, Y},
title = {Associations of adherence to a healthy sleep pattern with the dementia risk in the UK biobank.},
journal = {Alzheimer's research & therapy},
volume = {17},
number = {1},
pages = {213},
pmid = {41029423},
issn = {1758-9193},
support = {2022YFC3602600, 2023YFC3603200//National Key R&D Program of China/ ; 2022YFC3602600, 2023YFC3603200//National Key R&D Program of China/ ; QML20230802//Beijing Hospitals Authority Youth Program/ ; 82220108009,82401664//National Natural Science Foundation of China/ ; 82220108009,82401664//National Natural Science Foundation of China/ ; 2021ZD0201801//STI2030-Major Projects/ ; },
mesh = {Humans ; Male ; Female ; United Kingdom/epidemiology ; *Dementia/epidemiology ; Middle Aged ; Aged ; *Sleep/physiology ; Biological Specimen Banks ; Adult ; Magnetic Resonance Imaging ; Risk Factors ; Brain/diagnostic imaging ; Surveys and Questionnaires ; UK Biobank ; },
abstract = {BACKGROUND: Existing evidence highlights associations between sleep behaviors and dementia risk; however, the impact of adhering to a healthy sleep pattern on dementia risk remains unclear.

METHODS: Of 406,364 UK Biobank participants aged 40-64, we excluded those who had withdrawn, had incomplete sleep data, or had dementia at baseline, yielding a final sample of 333,014. Participants were enrolled between 2006 and 2010, with follow-up extending from recruitment to dementia diagnosis, death, loss to follow-up, or the censoring date (December 2022), whichever came first. Incident dementia was identified using hospital inpatient and death records, along with primary care data, with cases diagnosed at a mean age of 70.0 years (standard deviation [SD]: 5.6). Sleep-related questionnaire items from the UK Biobank were summarized into five sleep behaviors: sleeping 7-8 h daily, early chronotype, absence of frequent insomnia, no snoring, and no frequent daytime sleepiness. Each behavior meeting the healthy criterion was assigned one point, resulting in a total range from 0 to 5, with higher scores indicating better adherence to a healthy sleep pattern. Cox proportional hazards models were used to assess the association between healthy sleep patterns and dementia risk, adjusting for demographics, lifestyle factors, and medical history. A subset of 33,401 participants underwent brain magnetic resonance imaging (MRI) scans during the 9.4-year median period between sleep assessment and imaging. The imaging analysis included total brain volume, gray matter volume, white matter volume, hippocampal volume, and white matter hyperintensities (WMH).

RESULTS: During a median follow-up of 13.8 years, 3,035 incident dementia cases were recorded, including 1,304 Alzheimer's disease (AD) cases and 597 vascular dementia (VD) cases. A higher adherence to a healthy sleep pattern was associated with a lower dementia risk. Each 1-point increase in the healthy sleep score corresponded to a 7% reduction in dementia risk (Hazard Ratio [HR] = 0.93, 95% Confidence Interval [CI]: 0.89-0.96). Compared to participants with a score of 0-1, those with a score of 5 had a significantly lower risk of dementia (HR = 0.75, 95% CI: 0.61-0.92). Benefits were more pronounced in adults aged 40-55 years than those aged 56-64 years (p for interaction < 0.001). Adherence to a healthy sleep pattern was associated with increased grey matter volume and decreased WMH volume (all p < 0.05). Mediation analysis indicates that preserving grey and white matter integrity partially mediated the dementia-risk-lowering benefit (p < 0.05).

CONCLUSIONS: Adherence to a healthy sleep pattern is associated with both a reduced risk of dementia and greater white matter integrity, underscoring the role of improving overall sleep behaviors to support brain structure and lower dementia risk.},
}

Humans
Male
Female
United Kingdom/epidemiology
*Dementia/epidemiology
Middle Aged
Aged
*Sleep/physiology
Biological Specimen Banks
Adult
Magnetic Resonance Imaging
Risk Factors
Brain/diagnostic imaging
Surveys and Questionnaires
UK Biobank

@article {pmid41029418,
year = {2025},
author = {Contreras, JA and Ortega, NE and Espejo, K and Aslanyan, V and Pa, J and , },
title = {The effect of APOE4 on Alzheimer's plasma biomarkers among Mexican Americans in the HABS-HD cohort.},
journal = {Alzheimer's research & therapy},
volume = {17},
number = {1},
pages = {208},
pmid = {41029418},
issn = {1758-9193},
support = {U19AG078109//HABS-HD HESP/ ; U19AG078109//HABS-HD HESP/ ; P30AG059299//AD-RCMAR/ ; },
mesh = {Humans ; Female ; Male ; *Alzheimer Disease/blood/genetics/ethnology ; Biomarkers/blood ; *Apolipoprotein E4/genetics ; *Mexican Americans/genetics ; Aged ; Cross-Sectional Studies ; Amyloid beta-Peptides/blood ; Middle Aged ; tau Proteins/blood ; White People/genetics ; Cohort Studies ; Aged, 80 and over ; Peptide Fragments/blood ; White ; },
abstract = {BACKGROUND AND OBJECTIVES: The relationship between APOE4 status and plasma biomarkers previously shown to be related to Alzheimer's risk have not been carefully examined among Mexican Americans. This research is needed to elucidate disparities within the Alzheimer's field by evaluating key genetic factors in an underrepresented population. The present study deepens our understanding of the interaction between biological and genetic factors for these populations with greater incidence of Alzheimer's disease (AD) and helps address whether APOE4 confers similar risk of AD in Mexican Americans as previously reported in Non-Hispanic Whites.

METHODS: Cross-sectional data consisting of 792 Mexican American and 785 Non-Hispanic White participants from the Health & Aging Brain Study - Health Disparities (HABS-HD) with available plasma biomarkers and APOE4 genotype profiles were included in the present study. Linear regression models were used to test our hypotheses. APOE4-Race/ethnicity interaction term tested whether the biomarker levels differed between ethnic groups. Analyses were adjusted for age, gender, and education. Further analyses explored whether biomarker levels differed by APOE4 carrier status within racial/ethnic groups.

RESULTS: Among 1577 participants (59.5% women; mean age 66.4 ± 8.74 years), significant differences were observed across race/ethnic and APOE4 groups. Mexican Americans were younger (p < 0.001), had a higher proportion of women (p = 0.001), fewer years of education (p < 0.001), and lower MMSE scores (p < 0.001). Biomarker differences between Mexican Americans and Non-Hispanic Whites included variations in Aβ42/Aβ40 (p = 0.03) and p-tau181 (p < 0.001), but not in total tau, TNF-α, or NfL levels (all p > 0.12). Race/ethnicity-APOE4 interactions were significant for Aβ42/Αβ40, p-tau181, and total tau (all p < 0.05) but not for NfL or TNF-α. APOE4 associations with Aβ42/Aβ40 and p-tau181 were significant in NH White participants (all p < 0.001) but not among Mexican Americans.

CONCLUSION: These findings will significantly contribute to understanding potential differences in the role of APOE4 and AD plasma biomarkers among Mexican Americans. This research has the potential to enhance preventive care and early diagnosis for populations with a higher incidence of AD.},
}

Humans
Female
Male
*Alzheimer Disease/blood/genetics/ethnology
Biomarkers/blood
*Apolipoprotein E4/genetics
*Mexican Americans/genetics
Aged
Cross-Sectional Studies
Amyloid beta-Peptides/blood
Middle Aged
tau Proteins/blood
White People/genetics
Cohort Studies
Aged, 80 and over
Peptide Fragments/blood
White

@article {pmid41029412,
year = {2025},
author = {Wu, MJ and Hsiao, IT and Lin, KJ and Wu, YM and Wu, KY},
title = {Cerebral amyloid-β, glucose metabolism and hippocampal volume in major depression with and without suspected non-Alzheimer pathophysiology (SNAP).},
journal = {Alzheimer's research & therapy},
volume = {17},
number = {1},
pages = {207},
pmid = {41029412},
issn = {1758-9193},
mesh = {Humans ; Male ; *Depressive Disorder, Major/metabolism/diagnostic imaging/pathology/physiopathology ; *Hippocampus/pathology/diagnostic imaging/metabolism ; Female ; *Amyloid beta-Peptides/metabolism ; Middle Aged ; *Glucose/metabolism ; Cross-Sectional Studies ; Positron-Emission Tomography ; Magnetic Resonance Imaging ; Aged ; Alzheimer Disease ; },
abstract = {BACKGROUND: Major depressive disorder (MDD) can encompass suspected non-Alzheimer's disease pathophysiology (SNAP), characterized by negative cerebral Amyloid-β (Aβ) and positive neurodegeneration (ND) biomarkers. Relationships among cerebral Aβ deposition, glucose metabolism, and hippocampal volume in SNAP and non-SNAP MDD groups remain unclear.

METHODS: We conducted cross-sectional analyses of 136 MDD patients (enrolment age ≥ 50 years), classified into SNAP (n = 71) and non-SNAP (n = 65) groups. Dual-phase [18]F-florbetapir (AV45) PET/MR scans provided early-phase (as a proxy for glucose metabolism) and late-phase (reflecting Aβ deposition) images. Bilateral adjusted hippocampal volume (HVa) was measured using MRI. Partial correlations and multiple regression analyses examined the associations among Aβ deposition, metabolism, HVa, and depression-related variables.

RESULTS: In the non-SNAP MDD, greater Aβ deposition was associated with reduced glucose metabolism and smaller HVa, while HVa positively correlated with metabolism. Glucose metabolism partially mediated the relationship between Aβ deposition and both hippocampal atrophy and cognition function. In the SNAP MDD group, lower Aβ deposition was associated with lower glucose metabolism. While more lifetime depressive episodes were related to smaller HVa, depression severity showed a positive correlation with HVa. Additional subgroup analyses stratified by age and Aβ/ND status were also conducted.

CONCLUSIONS: These findings suggest distinct biological patterns in SNAP and non-SNAP MDD. Age- and biomarker (Aβ/ND)-stratified analyses yielded consistent Aβ-metabolism-atrophy profiles; however, the biomarker-stratified results should be interpreted with caution due to limited sample sizes. Notably, the non-SNAP group comprises biologically heterogeneous subgroups, which may obscure important distinctions and limit the interpretability of pooled findings. These results underscore the need for subgroup-specific approaches to better elucidate the pathophysiology of MDD.},
}

Humans
Male
*Depressive Disorder, Major/metabolism/diagnostic imaging/pathology/physiopathology
*Hippocampus/pathology/diagnostic imaging/metabolism
Female
*Amyloid beta-Peptides/metabolism
Middle Aged
*Glucose/metabolism
Cross-Sectional Studies
Positron-Emission Tomography
Magnetic Resonance Imaging
Aged
Alzheimer Disease

@article {pmid41029146,
year = {2025},
author = {Zhu, X and Chen, W and Zhuo, G and Yang, C and Fu, Y and Huang, Y and Zhang, Y and Liao, H and Wu, L},
title = {Mapping cerebrospinal fluid biomarkers to dementia risk through Mendelian randomization.},
journal = {Medicine},
volume = {104},
number = {39},
pages = {e44658},
doi = {10.1097/MD.0000000000044658},
pmid = {41029146},
issn = {1536-5964},
mesh = {Humans ; *Mendelian Randomization Analysis ; *Biomarkers/cerebrospinal fluid ; *Dementia/cerebrospinal fluid/genetics ; Alzheimer Disease/cerebrospinal fluid/genetics ; Genetic Predisposition to Disease ; Frontotemporal Dementia/cerebrospinal fluid/genetics ; Dementia, Vascular/cerebrospinal fluid/genetics ; },
abstract = {Cerebrospinal fluid (CSF) biomarkers can directly reflect physiological and pathological changes within the central nervous system, serving as a critical element in the preliminary diagnosis and disease monitoring of central nervous system disorders. Specific CSF biomarker patterns may be associated with different types of dementia. The goal of this analysis is to scrutinize the causal correlation between 338 CSF biomarkers and the danger of 4 dementia categories, namely Alzheimer disease, vascular dementia, frontotemporal dementia, and dementia with Lewy bodies, using Mendelian randomization (MR) analysis. Forward and reverse MR were employed to examine this causal relationship. Inverse variance weighting was used as the primary statistical method, with weighted median, MR-Egger, simple mode, and weighted mode methods as supplementary approaches. Concurrently, scrutiny of horizontal pleiotropy, heterogeneity, and sensitivity was undertaken to substantiate the inferences made from the MR study. We identified 9 positive and 12 negative causal relationships between genetic predisposition to CSF biomarkers and dementia. Notably, a bidirectional causal relationship was found between 3-methoxytyrosine levels and Alzheimer disease. The findings of this MR study support a causal association between CSF biomarkers and the risk of 4 distinct types of dementia.},
}

Humans
*Mendelian Randomization Analysis
*Biomarkers/cerebrospinal fluid
*Dementia/cerebrospinal fluid/genetics
Alzheimer Disease/cerebrospinal fluid/genetics
Genetic Predisposition to Disease
Frontotemporal Dementia/cerebrospinal fluid/genetics
Dementia, Vascular/cerebrospinal fluid/genetics

@article {pmid41029036,
year = {2025},
author = {Zhang, B and Bao, D and Ma, Y and Zhang, M and Cao, Y},
title = {Effects of different levels of alcohol consumption on cognitive function in older adults: A cross-sectional study using 2011 to 2014 NHANES data.},
journal = {Medicine},
volume = {104},
number = {39},
pages = {e44853},
doi = {10.1097/MD.0000000000044853},
pmid = {41029036},
issn = {1536-5964},
mesh = {Humans ; Female ; Male ; Aged ; Cross-Sectional Studies ; *Alcohol Drinking/epidemiology/adverse effects/psychology ; Middle Aged ; Nutrition Surveys ; United States/epidemiology ; *Cognition/drug effects ; *Cognitive Dysfunction/epidemiology/etiology ; Aged, 80 and over ; Risk Factors ; Neuropsychological Tests ; },
abstract = {Older adults (≥60 years) are at high risk for cognitive impairment, yet the impact of varying levels of alcohol consumption on cognitive function in this population remains unclear. This study aims to evaluate the effect of alcohol consumption on cognitive function among older adults in the United States. Researchers obtained data from 3632 participants aged 60 years and older from the 2011 to 2014 National Health and Nutrition Examination Survey. Alcohol consumption was assessed using a questionnaire, while cognitive function was evaluated using the Word Learning and Recall module from the Consortium to Establish a Registry for Alzheimer Disease, the Animal Fluency Test, and the Digit Symbol Substitution Test. The relationship between alcohol consumption and cognitive function was analyzed using weighted multivariable linear regression and stratified analysis based on key covariates. Fully adjusted Model 3 indicated that, compared to nondrinkers, light drinkers had an increase in cognitive function scores by 0.44 (β = 0.44, 95% confidence intervals [CI]: 0.20-0.67; P < .001), while moderate and heavy drinkers experienced a decline in cognitive function scores by 0.62 (β = -0.62, 95% CI: -0.89 to -0.34; P < .001) and 0.97 (β = -0.97, 95% CI: -1.23 to -0.62; P < .001), respectively. Stratified analysis revealed that heavy drinking had a more detrimental effect on cognition among individuals aged 70 and older, women, those with less than a high school education, and those with diabetes, hypertension, or a history of stroke. In older adults (≥60 years) in the United States, heavy alcohol consumption is associated with a decline in cognitive scores, particularly among those aged 70 and older, women, individuals with less than a high school education, and those with diabetes, hypertension, or a history of stroke.},
}

Humans
Female
Male
Aged
Cross-Sectional Studies
*Alcohol Drinking/epidemiology/adverse effects/psychology
Middle Aged
Nutrition Surveys
United States/epidemiology
*Cognition/drug effects
*Cognitive Dysfunction/epidemiology/etiology
Aged, 80 and over
Risk Factors
Neuropsychological Tests

@article {pmid41029023,
year = {2025},
author = {Yeerkenbieke, D and Guan, Y and Cui, J and Zhang, Q and Wang, G and Zhou, Y and Li, Z and Wang, C and Wang, D},
title = {Ginsenoside Rg2 Ameliorates Alzheimer's Disease by Alleviating Neuroinflammation in APP/PS1 Mice.},
journal = {Current neuropharmacology},
volume = {},
number = {},
pages = {},
doi = {10.2174/011570159X395496250911104139},
pmid = {41029023},
issn = {1875-6190},
abstract = {INTRODUCTION: Ginsenoside Rg2 (GRg2), a naturally occurring triterpenoid derived from ginseng rhizomes, exhibits neuroprotective properties. Neuroinflammation is recognized as one of the key pathogenic mechanisms underlying Alzheimer's disease (AD). This research aims to investigate the beneficial effects of GRg2 on AD and explore its potential mechanisms.

METHODS: In APP/PS1 mice, cognitive and behavioral assessments were first performed. Subsequently, brain tissue analyses were performed using immunohistochemical analysis and Western blot. A combined analysis of the gut microbiome and metabolomics was conducted to explore potential mechanisms. Finally, key findings were further validated through immunofluorescence and enzymelinked immunosorbent assay.

RESULTS: GRg2 enhanced learning, memory, and cognitive functions. And inhibits the deposition of β- amyloid and phosphorylated tau. GRg2 effectively inhibits the production of Bacteroides and Helicobacter. In addition, it reduced the levels of pyruvaldehyde and trimethylamine N-oxide, metabolites closely related to neuroinflammation. GRg2 effectively inhibited the activation of astrocytes and microglia in the brains of APP/PS1 mice, and also reduced the expression of neuroinflammatory mediators IL-6, IL-1β, and TNF-α.

DISCUSSIONS: The findings of this study substantiate the neuroprotective efficacy of GRg2, providing a novel therapeutic strategy and theoretical foundation for natural product-based interventions against AD.

CONCLUSION: GRg2 improves cognitive function and mitigates AD pathology, which is at least partially attributed to its regulation of gut microbiota and metabolites, as well as its anti-neuroinflammatory effects.},
}

@article {pmid41028758,
year = {2025},
author = {Thew, HY and Lim, WM and Ong, YS and Ong, LK and Parat, MO and Goh, BH and Khaw, KY},
title = {Garcinone D mitigates amyloid β42-Induced neurotoxicity: unravelling mechanisms of neuroprotection.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {33757},
pmid = {41028758},
issn = {2045-2322},
mesh = {*Amyloid beta-Peptides/toxicity/metabolism ; *Neuroprotective Agents/pharmacology ; *Peptide Fragments/toxicity ; *Xanthones/pharmacology ; Apoptosis/drug effects ; Reactive Oxygen Species/metabolism ; Mitochondria/drug effects/metabolism ; Humans ; Oxidative Stress/drug effects ; *Neurons/drug effects/metabolism ; Cell Survival/drug effects ; Alzheimer Disease/drug therapy/metabolism/pathology ; NF-E2-Related Factor 2/metabolism ; Animals ; *Neuroprotection/drug effects ; },
abstract = {Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the accumulation of Aβ42 peptides, which contribute to oxidative stress, apoptosis, and mitochondrial dysfunction in neurons. Garcinone D (GD), a bioactive xanthone derived from mangosteen, has shown promise as a neuroprotective agent; however, its mechanisms of action against Aβ42-induced neurotoxicity remain insufficiently defined. This study examined the protective effects of GD in Aβ42-treated neuronal cells, focusing on key molecular pathways. Our results demonstrate that GD significantly enhances cell viability and stabilizes mitochondrial function while reducing reactive oxygen species and apoptotic markers in Aβ42-treated cells. Additionally, GD activates key antioxidant pathways involving Nrf2 and HO-1, and inhibits caspase activity, thereby demonstrating a multifaceted approach to neuroprotection. These findings suggest that GD could serve as a valuable therapeutic candidate for AD by addressing multiple aspects of cellular damage that contribute to neurodegeneration. By promoting mitochondrial health while modulating oxidative and apoptotic pathways, GD shows potential for advancing therapeutic strategies in neurodegenerative disorders.},
}

*Amyloid beta-Peptides/toxicity/metabolism
*Neuroprotective Agents/pharmacology
*Peptide Fragments/toxicity
*Xanthones/pharmacology
Apoptosis/drug effects
Reactive Oxygen Species/metabolism
Mitochondria/drug effects/metabolism
Humans
Oxidative Stress/drug effects
*Neurons/drug effects/metabolism
Cell Survival/drug effects
Alzheimer Disease/drug therapy/metabolism/pathology
NF-E2-Related Factor 2/metabolism
Animals
*Neuroprotection/drug effects

@article {pmid41028649,
year = {2025},
author = {Gupta, P and Dutta, S and Dutta, K and Bhattacharjee, P and Hazra, A and Jash, R},
title = {Interconnection between gut microbial metabolites and mitochondrial ROS production: implications for cellular health.},
journal = {Molecular and cellular biochemistry},
volume = {},
number = {},
pages = {},
pmid = {41028649},
issn = {1573-4919},
abstract = {Trillions of microbes inhabit the human gut and engage in diverse biological processes by secreting different metabolites. These metabolites influence mitochondrial function and produce ROS. This gut-mitochondrial communication plays a pivotal role in regulating cellular homeostasis, energy production, and oxidative stress management, all required for optimal health. Short-chain fatty acids, secondary bile acids, amines, and gaseous metabolites are major gut metabolites that aid in governing mitochondrial processes to facilitate effective energy production and avoid oxidative damage. In the case of damaged mitochondrial function, it can alter gut flora (dysbiosis), resulting in inflammation and assisting a number of diseases such as multiple sclerosis, Alzheimer's disease, IgA nephropathy, inflammatory bowel disease, and colorectal cancer. The gut-mitochondria axis is a multifaceted interaction that regulates a cell's energy homeostasis and provides novel therapeutic opportunities. Probiotics, prebiotics, dietary modifications, and metabolite therapies have the potential to restore gut-microbe balance, enhance mitochondrial function, and reduce oxidative stress. These measures have the potential for new treatments for many diseases by modulating the gut-mitochondria axis. This review surveys interactions among gut microbiota, mitochondrial ROS, and the gut-mitochondria axis, describing how such relationships affect health and disease.},
}

@article {pmid41028329,
year = {2025},
author = {, and Boquet-Pujadas, A and Anagnostakis, F and Duggan, MR and Joynes, CM and Toga, AW and Yang, Z and Walker, KA and Davatzikos, C and Wen, J},
title = {Brain-heart-eye axis revealed by multi-organ imaging genetics and proteomics.},
journal = {Nature biomedical engineering},
volume = {},
number = {},
pages = {},
pmid = {41028329},
issn = {2157-846X},
support = {RF1AG092412//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; },
abstract = {Multi-organ research investigates interconnections among multiple human organ systems, enhancing our understanding of human aging and disease mechanisms. Here we use multi-organ imaging, individual- and summary-level genetics, and proteomics data consolidated via the MULTI Consortium to delineate a brain-heart-eye axis using brain patterns of structural covariance (PSCs), heart imaging-derived phenotypes (IDPs) and eye IDPs. We find that proteome-wide associations of the PSCs and IDPs show within-organ specificity and cross-organ interconnections. Pleiotropic effects of common single-nucleotide polymorphisms are observed across multiple organs, and key genetic parameters are estimated for single-nucleotide polymorphism-based heritability, polygenicity and selection signatures across the three organs. A gene-drug-disease network shows the potential of drug repurposing for cross-organ diseases. Co-localization and causal analyses reveal cross-organ causal relationships between PSC/IDP and chronic diseases, such as Alzheimer's disease, heart failure and glaucoma. Finally, integrating multi-organ/omics features improves prediction for systemic disease categories and cognition compared with single-organ/omics features, providing future avenues for modelling human aging and disease.},
}

@article {pmid41028277,
year = {2025},
author = {Noke Durden, W and Stolen, MK and Garamszegi, SP and Banack, SA and Brzostowicki, DJ and Vontell, RT and Brand, LE and Cox, PA and Davis, DA},
title = {Alzheimer's disease signatures in the brain transcriptome of Estuarine Dolphins.},
journal = {Communications biology},
volume = {8},
number = {1},
pages = {1400},
pmid = {41028277},
issn = {2399-3642},
mesh = {Animals ; *Transcriptome ; *Alzheimer Disease/genetics/metabolism ; *Brain/metabolism/pathology ; Harmful Algal Bloom ; Florida ; *Dolphins/genetics ; Seasons ; },
abstract = {Climate warming is one factor increasing the severity of harmful algal blooms (HABs). Innovative exposure models are needed to understand how HABs affect brain health. Here, we examined HAB exposure on the brain transcriptome of dolphins found stranded in Florida's Indian River Lagoon. We report the neurotoxin 2,4-diaminobutyric acid (2,4-DAB) is 2900 times more concentrated in dolphin brains during bloom seasons compared to non-bloom seasons. The same dolphins show 536 differentially expressed genes whose enrichment reveal impairment in GABAergic synapses, basement membrane alteration, and Alzheimer's disease (AD) risk factors that increase with each subsequent season. Dolphins also display concurrent AD-like neuropathological changes and elevated AD gene expression with 2,4-DAB exposure. Our study demonstrates disproportionate seasonal exposure to 2,4-DAB increases AD signatures in the brain transcriptome. As our climate warms, HABs will continue to intensify. Understanding the impact of HAB exposures will help to identify populations at risk for neurological illnesses.},
}

Animals
*Transcriptome
*Alzheimer Disease/genetics/metabolism
*Brain/metabolism/pathology
Harmful Algal Bloom
Florida
*Dolphins/genetics
Seasons

@article {pmid41028094,
year = {2025},
author = {Raj, AS and Gunasundari, C and Senthilkumar, S and Sivamani, S},
title = {An optimized hybrid deep learning model to detect Alzheimer disease.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {34081},
pmid = {41028094},
issn = {2045-2322},
mesh = {*Alzheimer Disease/diagnosis ; *Deep Learning ; Humans ; Algorithms ; Cognitive Dysfunction/diagnosis ; },
abstract = {Alzheimer's is a serious neurodegenerative disease that requires early detection for effective intervention. Traditional methods often struggle with accurately identifying the early stages, such as mild cognitive impairment (MCI), due to limitations in feature extraction and classification. To address these challenges, we present an optimized hybrid deep learning model for Alzheimer's disease detection. Our model employs the Inception v3 algorithm for initial feature extraction and the ResNet 50 algorithm for classification. Additionally, we optimize the network parameters using the Adaptive Rider Optimization (ARO) algorithm to enhance detection performance. Experimental analysis using a benchmark dementia dataset demonstrates that our model achieves superior accuracy of 96.6%, precision of 98%, recall of 97%, and F1-score of 98%, outperforming state-of-the-art techniques.},
}

*Alzheimer Disease/diagnosis
*Deep Learning
Humans
Algorithms
Cognitive Dysfunction/diagnosis

@article {pmid41028047,
year = {2025},
author = {Khan, MI and Jeong, ES and Tasreen, G and Khan, MZ and Shin, JH and Kim, JD},
title = {The therapeutic potential of beta-carotene against neuroinflammation and amyloid beta in SH-SY5Y cells.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {33803},
pmid = {41028047},
issn = {2045-2322},
support = {NRF-2018R1D1A1B07047021//National Research Foundation of Korea/ ; },
mesh = {Humans ; *beta Carotene/pharmacology ; *Amyloid beta-Peptides/metabolism ; Cell Line, Tumor ; Apoptosis/drug effects ; *Neuroprotective Agents/pharmacology ; Antioxidants/pharmacology ; *Neuroinflammatory Diseases/drug therapy/metabolism/pathology ; Alzheimer Disease/drug therapy/metabolism ; Amyloid Precursor Protein Secretases/metabolism ; },
abstract = {Neurodegenerative diseases, particularly Alzheimer's disease (AD), represent a significant public health challenge due to their increasing prevalence and the lack of effective treatments. In this study, we explored the neuroprotective effects of beta-carotene, a naturally occurring carotenoid, by investigating its ability to inhibit or reduce apoptosis and inflammation while enhancing antioxidant potential in SH-SY5Y neuroblastoma cells. Beta-carotene was extracted from Chlorella vulgaris using high-performance liquid chromatography (HPLC). We utilized SH-SY5Y cells, a widely employed in vitro model for studying neurodegenerative processes, to evaluate these therapeutic effects. A combination of colorimetric assays, enzyme-linked immunosorbent assays (ELISA), and quantitative real-time PCR (qRT-PCR) was used to assess the impact of beta-carotene on enzyme activity, cytokine production, and gene expression. The caspase assay results demonstrated that beta-carotene effectively reduced the activity of pro-apoptotic caspases and downregulated the expression of pro-apoptotic genes such as Bax, Bak and caspases, thereby inhibiting apoptosis in SH-SY5Y cells. Additionally, beta-carotene exhibited potent antioxidant properties by upregulating NRF2 and superoxide dismutase (SOD), along with enhancing ABTS and DPPH radical scavenging activities.showed antiinflamatory effects reduce the concentrations of proinflamatory cytokines TNFα, IL-1 β and IFN-γ, and supress the inflamtion patway by supressing the expression of Akt, PIK3, STAT1 and NF-kB, Akt etc. Importantly, beta-carotene treatment led to the suppression of β-secretase (BACE1), γ-secretase and acetylcholinesterase (AChE) activities, and the downregulation of genes involved in amyloid-beta production, including BACE1, and PECN1 eventualy resulted in dcerase concentration o Aβ peptides. These findings suggest that β-carotene could be a promising therapeutic candidate for the prevention and treatment of neurodegenerative diseases, particularly Alzheimer's disease, however further investigations are recomended in animal models and clinical trials before incorporating beta-cerotene into pharmaceutical formulations for AD treatment.},
}

Humans
*beta Carotene/pharmacology
*Amyloid beta-Peptides/metabolism
Cell Line, Tumor
Apoptosis/drug effects
*Neuroprotective Agents/pharmacology
Antioxidants/pharmacology
*Neuroinflammatory Diseases/drug therapy/metabolism/pathology
Alzheimer Disease/drug therapy/metabolism
Amyloid Precursor Protein Secretases/metabolism

@article {pmid41027951,
year = {2025},
author = {Sriram, S and Nivethitha, V and Arun Kaarthic, TP and Archita, S and Murugan, T},
title = {Advanced MRI based Alzheimer's diagnosis through ensemble learning techniques.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {33840},
pmid = {41027951},
issn = {2045-2322},
mesh = {*Alzheimer Disease/diagnostic imaging/diagnosis ; Humans ; *Magnetic Resonance Imaging/methods ; Deep Learning ; Neural Networks, Computer ; *Brain/diagnostic imaging ; *Machine Learning ; Aged ; Male ; Female ; Ensemble Learning ; },
abstract = {Alzheimer's Disease is a condition that affects the brain and causes changes in behavior and memory loss while making it hard to carry out tasks properly. It's vital to spot the illness early, for effective treatment. MRI technology has advanced in detecting Alzheimer's by using machine learning and deep learning models. These models use neural networks to analyze brain MRI results automatically and identify key indicators of Alzheimer's disease. In this study, we used MRI data to train a CNN for diagnosing and categorizing the four stages of Alzheimer's disease with deep learning techniques, offering significant advantages in identifying patterns in medical imaging for this neurodegenerative condition compared to using a CNN exclusively trained for this purpose. They evaluated ResNet50, InceptionResNetv2 as well as a CNN specifically trained for their study and found that combining the models led to highly accurate results. The accuracy rates for the trained CNN model stood at 90.76%, InceptionResNetv2 at 86.84%, and ResNet50 at 90.27%. In this trial run of the experiment conducted by combining all three models collaboratively resulted in an accuracy rate of 94.27% compared to the accuracy rates of each model working individually.},
}

*Alzheimer Disease/diagnostic imaging/diagnosis
Humans
*Magnetic Resonance Imaging/methods
Deep Learning
Neural Networks, Computer
*Brain/diagnostic imaging
*Machine Learning
Aged
Male
Female
Ensemble Learning

@article {pmid41027849,
year = {2025},
author = {Abughofah, Y and Risacher, SL and Unverzagt, FW and Farlow, MR and Apostolova, LG and Brosch, JR and Clark, DG and Mathew, S and Gao, S and Wang, S and Wang, S and Saykin, AJ},
title = {The Cognitive Change Index in the Alzheimer's Disease Research Center setting: Self- and informant-ratings for perceived cognitive decline.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21},
number = {10},
pages = {e70754},
doi = {10.1002/alz.70754},
pmid = {41027849},
issn = {1552-5279},
support = {P30 AG072976/AG/NIA NIH HHS/United States ; P30 AG10133/AG/NIA NIH HHS/United States ; R01 AG19771/AG/NIA NIH HHS/United States ; K01 AG049050/AG/NIA NIH HHS/United States ; R01 AG061788/AG/NIA NIH HHS/United States ; R01 AG057739/AG/NIA NIH HHS/United States ; U19 AG024904/AG/NIA NIH HHS/United States ; R01 LM013463/AG/NIA NIH HHS/United States ; R01 AG068193/AG/NIA NIH HHS/United States ; R01 AG092591/AG/NIA NIH HHS/United States ; T32 AG071444/AG/NIA NIH HHS/United States ; U01 AG068057/AG/NIA NIH HHS/United States ; U01 AG072177/AG/NIA NIH HHS/United States ; U19 AG074879/AG/NIA NIH HHS/United States ; U24 AG074855/AG/NIA NIH HHS/United States ; K07AG076659/AG/NIA NIH HHS/United States ; //Donor's Cure Foundation/ ; },
mesh = {Humans ; Female ; Male ; *Cognitive Dysfunction/diagnosis/psychology ; *Alzheimer Disease/diagnosis/psychology ; Aged ; *Neuropsychological Tests ; Surveys and Questionnaires ; Aged, 80 and over ; Indiana ; ROC Curve ; },
abstract = {INTRODUCTION: The Cognitive Change Index (CCI) is a brief questionnaire that assesses self and informant perceptions regarding cognitive function. We examined the ability of the CCI to distinguish between cognitively unimpaired (CU) older adults and those with mild cognitive impairment (MCI) or Alzheimer's disease (AD) dementia.

METHODS: 485 individuals from the Indiana Alzheimer's Disease Research Center (IADRC) and their study partners completed 20-item self and informant versions of the CCI. Receiver operator characteristic (ROC) curves were analyzed to assess differentiation between CU and those with impairment.

RESULTS: High area under the ROC curve (AUC) values were obtained when using the self and informant CCI forms to distinguish CU individuals from those with impairment, with AUC values of 0.803 (95% confidence interval [CI] = 0.761-0.844) and 0.914 (95% CI = 0.886-0.942) for the self and informant forms, respectively.

DISCUSSION: The CCI can serve as a useful screening instrument in the context of a multimodal assessment strategy for MCI and dementia.

HIGHLIGHTS: Novel research that uses the Cognitive Change Index (CCI) for dementia screening. Our findings suggest that CCI can distinguish those with dementia compared to those without. These findings can be correlated to other screening instruments. Results could see the CCI play a role in early Alzheimer's disease (AD) screening and diagnosis.},
}

Humans
Female
Male
*Cognitive Dysfunction/diagnosis/psychology
*Alzheimer Disease/diagnosis/psychology
Aged
*Neuropsychological Tests
Surveys and Questionnaires
Aged, 80 and over
Indiana
ROC Curve

@article {pmid41027829,
year = {2025},
author = {Kumar, P and Mousavi, A and Frykman, H},
title = {The biological diagnosis of Alzheimer's disease using blood-based biomarkers: a Canadian prospective.},
journal = {Clinical biochemistry},
volume = {},
number = {},
pages = {111015},
doi = {10.1016/j.clinbiochem.2025.111015},
pmid = {41027829},
issn = {1873-2933},
abstract = {Dementia is the most common type of neurodegenerative disease, with Alzheimer's Disease (AD) constituting about two-thirds of these cases. In Canada, an estimated 674,000 individuals may have AD by 2031, nearly doubling from 2011. The total annual economic burden of dementia in Canada was about $40 billion in 2020, with an approximate average of $67,200 per person with dementia and if current trends continue, its annual burden could grow by 275 % over 30 years. AD is a double proteinopathy with its fundamental neuropathologic features defined by amyloid-beta (Aβ) plaques and neurofibrillary tangles with aggregated tau proteins. This supports the potential for mechanism-based proteomic biomarkers to be detected in biofluids. Pathophysiologic and topographical biomarkers have significantly improved the diagnosis of typical and atypical phenotypes of AD, helping clinicians recognize and differentiate AD phenotypes from other types of dementia and neurodegenerative diseases. The cerebrospinal fluid Aβ42/Aβ40 ratio measurement is a robust biomarker in detecting cerebral Aβ pathology and AD diagnosis. A number of very sensitive assays for measuring AD blood biomarkers including p-tau217, front-runner candidate for AD diagnosis, have been developed during last years. In this review we discuss the biological configuration and normal function of involved proteomics in AD including Aβ and tau protein, particularly tau phosphorylation and biochemistry of tau isoforms and their detection feasibility in plasma using novel technologies. Then, we critically review blood-based biomarkers' analytical and clinical validations, focusing more on plasma p-tau217 and their availability and prospects in Canada.},
}

@article {pmid41027737,
year = {2025},
author = {Dimitrov, D and Raja, S and Noor, H and Takahashi, T},
title = {Common Mechanism Underlying Synaptic Dysfunction Caused by Preformed Fibril-Induced Accumulation of α-Synuclein or Tau in a Culture Propagation Model.},
journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1523/JNEUROSCI.0394-25.2025},
pmid = {41027737},
issn = {1529-2401},
abstract = {In sporadic neurodegenerative diseases, the endogenous proteins α-synuclein in Parkinson's disease and tau in Alzheimer's disease undergo pathogenic prion-like propagation over many years, accumulating in both soluble and insoluble forms in neurons including synapses, where they impair synaptic transmission and potentially cause various neuronal symptoms. To investigate the functional outcome of such synaptic accumulation, we induced accumulation of endogenous proteins in murine and human synapses by incubating mouse (of either sex) neuronal cultures with pathogenic preformed fibrils (pffs). Two weeks after treatment with human α-synuclein or tau pff, the respective endogenous proteins accumulated in neurons including presynaptic terminals, where we also observed tubulin accumulation, suggesting microtubule over-assembly. These were not associated with mRNA upregulation and were prevented by pharmacological stimulation of autophagy. Both pffs caused accumulation of p62 in cell bodies, suggesting compromised protein degradation. pHluorin imaging in synapses indicated a marked prolongation of vesicular endocytic time, which was rescued by pharmacological depolymerization of microtubules or by the over-expression of full-length dynamin 1. Since dynamin is a high-affinity binding partner of microtubules as well as an endocytic key molecule, over-assembled microtubules can sequester dynamin, thereby inhibiting endocytosis. We conclude that pff-induced accumulation of α-synuclein or tau in presynaptic terminals can disrupt vesicle endocytosis through a common mechanism. Since endocytosis-dependent vesicle recycling is critical for maintaining neurotransmitter release, its disruption can affect the neurocircuitry operations involved, thereby causing diverse symptoms associated with neurodegenerative diseases. Thus, our data suggest a common molecular mechanism underlying synaptic dysfunctions associated with Parkinson's and Alzheimer's diseases.Significance statement The accumulation of the pathogenic proteins α-synuclein and tau drives prion-like trans-neuronal propagation and underlies distinct neurodegenerative diseases, such as Parkinson's and Alzheimer's disease. Using a synaptic culture model of protein propagation, we identified a shared mechanism of synaptic dysfunction caused by these otherwise distinct proteins. In our models, propagated α-synuclein or tau disrupt protein degradation pathways, leading to their accumulation. These accumulated proteins promote excessive microtubule assembly and sequester the key endocytic protein dynamin, eventually impairing synaptic vesicle endocytosis. This cascade results in synaptic dysfunction that could compromise neurocircuit operations critical for brain functions. Our clarification of these mechanistic steps will improve our understanding of the synaptic pathophysiology underlying diverse symptoms of distinct neurodegenerative diseases.},
}

@article {pmid41027722,
year = {2025},
author = {Nogrady, B},
title = {Lecanamab: Controversial Alzheimer's drug approved by Australian drugs regulator after two rejections.},
journal = {BMJ (Clinical research ed.)},
volume = {390},
number = {},
pages = {r2056},
doi = {10.1136/bmj.r2056},
pmid = {41027722},
issn = {1756-1833},
}

@article {pmid41027650,
year = {2025},
author = {Zhou, F and Zhao, Z and Dai, J and Xu, J and Jiang, K and Tong, Z},
title = {Olfactory Testing With Focus on Odor Identification for Early Detection of Alzheimer's Disease in Mild Cognitive Impairment.},
journal = {American journal of Alzheimer's disease and other dementias},
volume = {40},
number = {},
pages = {15333175251385615},
doi = {10.1177/15333175251385615},
pmid = {41027650},
issn = {1938-2731},
mesh = {Humans ; *Cognitive Dysfunction/diagnosis/physiopathology/complications ; *Alzheimer Disease/diagnosis/complications/physiopathology ; Early Diagnosis ; *Olfaction Disorders/diagnosis/etiology ; *Odorants ; *Smell/physiology ; *Olfactory Perception/physiology ; },
abstract = {This review examines the application of olfactory testing in the early stages of mild cognitive impairment (MCI) associated with Alzheimer's disease (AD), highlighting its potential and challenges in early screening and intervention. Olfactory function is typically divided into three domains: odor identification, odor discrimination, and odor threshold. Among these, odor identification and discrimination are closely linked to higher cognitive processes and exhibit significant impairment in patients with AD and MCI. Moreover, the anatomical and functional characteristics of the olfactory system make it a promising target for the early detection of neurodegenerative disorders. This review also outlines various olfactory assessment tools and evaluates their clinical utility. Future research should aim to enhance the accuracy and cultural adaptability of olfactory tests and integrate them with multimodal diagnostic approaches to advance early detection and intervention strategies for AD.},
}

Humans
*Cognitive Dysfunction/diagnosis/physiopathology/complications
*Alzheimer Disease/diagnosis/complications/physiopathology
Early Diagnosis
*Olfaction Disorders/diagnosis/etiology
*Odorants
*Smell/physiology
*Olfactory Perception/physiology

@article {pmid41027547,
year = {2025},
author = {Yu, Y and Zhou, RZ and Nilsson, P and Winblad, B and Tjernberg, LO and Schedin-Weiss, S},
title = {Altered APP trafficking drives amyloidogenic processing in primary neurons from the App[NL-F] knock-in mouse model of Alzheimer's disease.},
journal = {Neurobiology of disease},
volume = {},
number = {},
pages = {107129},
doi = {10.1016/j.nbd.2025.107129},
pmid = {41027547},
issn = {1095-953X},
abstract = {Self-assembly of the 42-residue long amyloid β-peptide (Aβ42) into neurotoxic aggregates - eventually leading to formation of amyloid plaques - is a key event in Alzheimer's disease (AD) pathogenesis. Still, the intracellular mechanisms leading to Aβ42 formation and aggregation in neurons are poorly defined. Here, we used the App[NL-F] knock-in mouse model to analyze the effect of Aβ42-induced pathology on the subcellular location of the Aβ precursor protein (APP), its C-terminal fragments (CTFs) and Aβ42 in primary neurons. Stimulated emission depletion (STED) microscopy was used to obtain super-resolution and enable colocalization analysis. APP/CTF levels were to a high extent found in clathrin-coated vesicles in the perinuclear region in soma in both wild-type and App[NL-F] neurons and significantly increased in early endosomes in neurites. In distal axons, increased colocalization of APP/CTF with the synaptic vesicle protein synaptophysin was observed. Western blotting showed a three-fold decrease in mature/immature APP in App[NL-F] neurons, and ELISA showed a 2.7 and 7.2-fold increase in intra- and extracellular Aβ42 levels, respectively. Interestingly, LAMP1-positive vesicles were larger in App[NL-F] neurons than in wild-type neurons. Thus, processing of APP and axonal transport of APP/CTFs is increased in App[NL-F] neurons, resulting in enhanced levels of the immediate Aβ precursor (CTFβ) at the presynapse. Hence, an increase in CTFβ levels at sites with high γ-secretase activity leads to increased formation and secretion of Aβ42. This, in turn, results in enhanced re-uptake of Aβ42 and enlarged Aβ42-containing late endosomes/lysosomes in soma, causing toxic downstream effects.},
}

@article {pmid41027526,
year = {2025},
author = {Vlachos, I and Moschovos, C and Apostolakopoulou, L and Karasavvidou, K and Ntanasi, E and Mamalaki, E and Kugiumtzis, D and Kimiskidis, VK and Scarmeas, N and Kyrozis, A},
title = {Resting EEG partial coherence demonstrates increased γ range central functional connectivity in amnestic mild cognitive impairment.},
journal = {Brain research},
volume = {},
number = {},
pages = {149973},
doi = {10.1016/j.brainres.2025.149973},
pmid = {41027526},
issn = {1872-6240},
abstract = {OBJECTIVE: Relatively little is known about EEG high γ (gamma) range changes in Alzheimer's disease (AD). We investigated functional connectivity, focusing on the γ range, in amnestic Mild Cognitive Impairment (MCI) using ordinary Coherence (COH) and Partial Coherence (PCOH), a metric which enhances signal to noise ratio at high frequencies.

METHODS: MCI (N=21) and Cognitively normal (CN, N=62) ALBION study participants had resting EEG with eyes closed (EC) and eyes open (EO) in 10/20 montage (19 active electrodes). COH and PCOH in 0.5 to 100 Hz for each subject were calculated for all 171 electrode pairs.

RESULTS: In both γ1 (30-50 Hz) and γ2 (50-100 Hz) ranges, PCOH was significantly higher in MCI than in CN in several electrode pairs, especially centrally, in both eye conditions. Concerning local (average of each electrode) connectivity, MCI compared to CN showed significantly higher values in PCOH centrally.

CONCLUSIONS: Resting EEG γ range functional connectivity at central areas, as revealed by PCOH, is significantly higher in MCI than in CN.

SIGNIFICANCE: γ range local and regional EEG functional connectivity differences may help construct useful and easily available biomarkers in neurodegeneration. Metrics, such as PCOH, which factor out global connectivity components may help reveal such differences.},
}

@article {pmid41027525,
year = {2025},
author = {Wang, Y and Zhao, D and Kong, T and Ni, Y and Liu, Y and Kang, Y and Wang, F},
title = {Associations between reproductive milestones and Alzheimer's disease risk: a Mendelian randomization study.},
journal = {Brain research},
volume = {1867},
number = {},
pages = {149972},
doi = {10.1016/j.brainres.2025.149972},
pmid = {41027525},
issn = {1872-6240},
abstract = {BACKGROUND: Alzheimer's disease (AD) is a prevalent neurodegenerative disorder. Previous studies have suggested associations between female reproductive history and AD risk, but the causal nature of these relationships remains unclear. This study aimed to investigate the causal relationships between key female reproductive milestones (age at menarche, age at first birth, and menopause) and AD risk using Mendelian randomization (MR) and multivariate MR analysis.

METHODS: Two-sample MR and multivariate MR analyses were conducted using pooled data from large-scale genome-wide association studies. Genetic variants associated with female reproductive milestones served as instrumental variables. Replication phase data were provided by the Medical Research Council Integrative Epidemiology Unit consortium. Core single-nucleotide polymorphisms were selected to examine the effects of age at menarche, age at first birth, and menopause on AD risk. The inverse variance weighting method was the primary analytical approach, with causality assessed using MR-Egger regression and weighted median estimation. Sensitivity analyses and pleiotropy assessments were performed using Cochran's Q test and the MR-PRESSO global test. This study followed the STROBE-MR checklist for reporting MR studies.

RESULTS: MR analysis revealed that genetically predicted earlier age at menarche and age at first birth are potentially associated with increased risk of AD (OR = 0.92, 95 % CI: 0.85-0.99, p = 0.022; OR = 0.90, 95 % CI: 0.84-0.96, p = 0.002, respectively). Conversely, genetically predicted menopause was associated with increased AD risk (OR = 2.55, 95 % CI: 1.06-6.14, p = 0.036).

CONCLUSION: This MR study provides evidence suggesting that genetically predicted age at menarche, age at first birth, and menopause are significantly associated with AD risk, operating independently of each other. These findings highlight the potential role of female reproductive milestones in AD pathogenesis.},
}

@article {pmid41026859,
year = {2025},
author = {Santambrogio, A and Lövestam, S and Metrick, MA and Löhr, T and Xu, P and Gallagher, NCT and Ghetti, B and Caughey, B and Scheres, SHW and Vendruscolo, M},
title = {Serial amplification of tau filaments using Alzheimer's brain homogenates and C322A or C322S recombinant tau.},
journal = {FEBS letters},
volume = {},
number = {},
pages = {},
doi = {10.1002/1873-3468.70141},
pmid = {41026859},
issn = {1873-3468},
support = {10059436//UK Research and Innovation/ ; 10061100//UK Research and Innovation/ ; },
abstract = {The assembly of tau into amyloid filaments is a hallmark of Alzheimer's disease (AD) and other tauopathies. Cryo-EM revealed the existence of disease-specific tau folds, which are challenging to replicate in vitro. We studied three full-length recombinant 0N3R tau forms (the wild-type and the C322A and C322S variants) using an RT-QuIC assay with brain homogenate seeding. C322A tau formed filaments resembling AD paired helical filaments (PHFs) but with a more open C-shaped core. C322S tau yielded structurally distinct filaments with an ordered C-terminal region. Both mutants seeded further aggregation, whereas the wild-type showed poor reproducibility and mainly unfolded aggregates. These results highlight the importance of optimised conditions to produce disease-relevant tau filaments and aid the development of targeted therapies. Impact statement We investigated the seeded assembly of 0N3R tau and its two mutational variants C322A and C322S, using Alzheimer's disease brain homogenates in a real-time quaking-induced conversion (RT-QuIC) assay. The C322A variant formed filaments partially resembling the AD PHF structure, showing the importance of optimised conditions to produce disease-relevant tau filaments.},
}

@article {pmid41026820,
year = {2025},
author = {Vasavda, C and Kothari, R and Ammal Kaidery, N and Chakraborty, S and Jamuna Tripathi, S and Dhindsa, RS and Ricco, C and Shanmukha, S and Saberi, S and Lefler, JE and Kothari, P and Chaubey, K and Snowman, AM and Ostrowski, MC and Barone, E and Iyer, LM and Aravind, L and Sharma, SM and Pieper, AA and Thomas, B and Snyder, SH and Paul, BD},
title = {Biliverdin reductase A is a major determinant of protective NRF2 signaling.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {122},
number = {40},
pages = {e2513120122},
doi = {10.1073/pnas.2513120122},
pmid = {41026820},
issn = {1091-6490},
support = {1R01AG071512//HHS | NIH | National Institute on Aging (NIA)/ ; 1R21AG073684//HHS | NIH | National Institute on Aging (NIA)/ ; P50 DA044123/DA/NIDA NIH HHS/United States ; AG077396//HHS | NIH | National Institute on Aging (NIA)/ ; NS101967//HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; NS133688//HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; HT94252310443//DOD | Department of Defense/ ; I01BX005976//U.S. Department of Veterans Affairs (VA)/ ; RO1AGs066707//HHS | NIH | National Institute on Aging (NIA)/ ; AG073323//HHS | NIH | National Institute on Aging (NIA)/ ; 19PABH134580006//American Heart Association (AHA)/ ; 19PABH134580006//American Heart Association (AHA)/ ; Catalyst Award//Johns Hopkins University (JHU)/ ; },
mesh = {*NF-E2-Related Factor 2/metabolism/genetics ; *Oxidoreductases Acting on CH-CH Group Donors/metabolism/genetics ; *Signal Transduction ; Animals ; Humans ; Mice ; Oxidation-Reduction ; Antioxidants/metabolism ; Brain/metabolism ; HEK293 Cells ; },
abstract = {Biliverdin reductase A (BVRA), the terminal enzyme in heme catabolism, generates the neuroprotective and lipophilic antioxidant bilirubin. Here, we identify a nonenzymatic role for BVRA in redox regulation. Through phylogenetic, genetic, biochemical, and enzymatic assays, we found that BVRA exerts critical nonenzymatic antioxidant activity. Transcriptomic analyses further revealed that BVRA physically and genetically interacts with nuclear factor erythroid-derived factor-like 2 (NRF2), a major transcriptional regulator of cellular redox signaling. ChIP-seq and RNA-seq analyses reveal that BVRA and NRF2 coordinate the expression of antioxidant genes, many of which are typically dysregulated in neurodegenerative conditions such as Alzheimer's disease. Thus, this noncanonical BVRA-NRF2 axis controls an essential pathway of redox signaling in neuroprotection. Our findings position BVRA as a dual-function integrator of antioxidant defense across both lipophilic and hydrophilic compartments, bridging these two distinct modes of redox protection in the brain.},
}

*NF-E2-Related Factor 2/metabolism/genetics
*Oxidoreductases Acting on CH-CH Group Donors/metabolism/genetics
*Signal Transduction
Animals
Humans
Mice
Oxidation-Reduction
Antioxidants/metabolism
Brain/metabolism
HEK293 Cells

@article {pmid41026750,
year = {2025},
author = {Kokorelias, KM and Stall, NM and Wasilewski, M and Gignac, MAM and Rittenberg, N and Singh, H and Dove, E and Harris, M and Beleno, R and Naglie, G and Cameron, JI},
title = {Navigating the dementia caregiving journey: A scoping review protocol of interventions and their responsiveness to caregivers' evolving needs across the illness trajectory.},
journal = {PloS one},
volume = {20},
number = {9},
pages = {e0333475},
doi = {10.1371/journal.pone.0333475},
pmid = {41026750},
issn = {1932-6203},
mesh = {Humans ; *Caregivers/psychology ; Scoping Review as Topic ; *Dementia/therapy/psychology ; *Alzheimer Disease ; Disease Progression ; },
abstract = {INTRODUCTION: Family caregivers of persons with dementia (PWD) provide critical and often sustained support across the dementia trajectory. Despite growing recognition of their evolving needs, many interventions remain episodic and not tailored to different caregiving phases. Frameworks like the Timing It Right (TIR) and the Caregiver-Identified Phases of Alzheimer's Disease (CIP-AD) offer structured approaches to understanding how caregiver needs change over time. However, little is known about whether current interventions align with these phase-specific needs.

OBJECTIVES: This scoping review aims to (1) explore the extent to which existing dementia caregiving interventions address different stages of the caregiving journey or dementia progression; (2) summarize and characterize these interventions using the Template for Intervention Description and Replication (TIDieR) checklist; and (3) identify characteristics of the populations targeted by these interventions.

METHODS: Following JBI methodology and the PRISMA-ScR checklist, we will conduct a scoping review of randomized controlled trials, non-randomized controlled trials, and quasi-experimental studies focused on interventions for unpaid family caregivers of community-dwelling PWD. Studies will be included if they address at least one phase of the dementia trajectory and are delivered in community-based settings. A comprehensive search of six databases from 1995 to 2025 will be developed and peer-reviewed using the PRESS framework. Data will be extracted using a standardized form and analyzed thematically.

SIGNIFICANCE: This review will map how dementia caregiving interventions address the evolving needs of caregivers over time and inform future development and implementation of phase-responsive support strategies. The findings will guide research, policy, and practice in creating caregiver-centered interventions that reflect the realities of caregiving across the dementia continuum.},
}

Humans
*Caregivers/psychology
Scoping Review as Topic
*Dementia/therapy/psychology
*Alzheimer Disease
Disease Progression

@article {pmid41026542,
year = {2025},
author = {Siddu, A and Natale, S and Wong, CH and Shaye, H and Südhof, TC},
title = {Aggregation shifts amyloid-β peptides from synaptogenic to synaptotoxic.},
journal = {The Journal of clinical investigation},
volume = {},
number = {},
pages = {},
doi = {10.1172/JCI193407},
pmid = {41026542},
issn = {1558-8238},
abstract = {Whether amyloid-β (Aβ) peptides are synaptogenic or synaptotoxic remains a pivotal open question in Alzheimer's disease research. Here, we chronically treated human neurons with precisely controlled concentrations of chemically defined synthetic Aβ40, Aβ42, and Aβ42arctic peptides that exhibit distinct aggregation propensities. Remarkably, chronic exposure of human neurons to free Aβ40 at higher concentrations or to free Aβ42 at lower concentrations potently promoted synapse formation. In contrast, aggregated Aβ42 or Aβ42arctic at higher concentrations were neurotoxic and synaptotoxic. The synaptotoxic effects of Aβ peptides manifested as an initial contraction of the synaptic vesicle cluster followed by synapse loss. Aβ40 and Aβ42 peptides with scrambled or inverted sequences were inactive. Thus, our experiments reveal that Aβ peptides exhibit an aggregation-dependent functional dichotomy that renders them either synaptogenic or synaptotoxic, thereby providing insight into how Aβ peptides straddle a thin line between physiological synapse organization and pathological synapse disruption. Among others, our data suggest that Alzheimer's disease therapies might aim to shift the balance of Aβ peptides from the aggregated to the free state instead of suppressing all Aβ peptides.},
}

@article {pmid41026247,
year = {2025},
author = {Wang, LF and Liu, X and Li, S and Li, R and Li, R and Yan, F and Jing, X},
title = {Comprehensive study of W06A7.4 and TMEM144 mediated pathways in aging: insights from Caenorhabditis elegans to human.},
journal = {Molecular genetics and genomics : MGG},
volume = {300},
number = {1},
pages = {95},
pmid = {41026247},
issn = {1617-4623},
support = {20231082//Gansu University of Chinese Medicine/ ; A2022047//Guangdong Medical Science Foundation project/ ; 82204655//National Natural Science Foundation of China/ ; 82200616//National Natural Science Foundation of China/ ; },
mesh = {*Caenorhabditis elegans/genetics/metabolism ; Humans ; Animals ; *Membrane Proteins/genetics/metabolism ; *Caenorhabditis elegans Proteins/genetics/metabolism ; *Aging/genetics/metabolism ; Signal Transduction ; Longevity/genetics ; Mitochondria/metabolism/genetics ; Oxidative Stress ; Alzheimer Disease/genetics/metabolism/pathology ; TOR Serine-Threonine Kinases/metabolism ; Membrane Potential, Mitochondrial ; },
abstract = {Aging is a major biological process underlying increased risk of chronic and neurodegenerative diseases, yet its molecular mechanisms remain incompletely defined. Our study systematically investigates the conserved functions and pathways of W06A7.4 in Caenorhabditis elegans and its human homolog TMEM144 in the regulation of aging, combining genetic manipulation in model organisms, analysis of human clinical samples, and functional assays in cell lines. The results demonstrate that W06A7.4 promotes longevity in C. elegans through synergistic effects with dietary restriction, reduction of oxidative damage, modulation of IIS and mTOR signaling, and maintenance of mitochondrial membrane potential. In human samples and cellular models, TMEM144 expression increases with age and in Alzheimer's disease. Our results suggest that TMEM144 may be involved in the regulation of glucose transport and mitochondrial respiration via the downstream protein TIMMDC1. These findings advance our understanding of evolutionarily conserved aging pathways and identify W06A7.4/TMEM144 as promising molecular targets for anti-aging and neurodegenerative disease interventions.},
}

*Caenorhabditis elegans/genetics/metabolism
Humans
Animals
*Membrane Proteins/genetics/metabolism
*Caenorhabditis elegans Proteins/genetics/metabolism
*Aging/genetics/metabolism
Signal Transduction
Longevity/genetics
Mitochondria/metabolism/genetics
Oxidative Stress
Alzheimer Disease/genetics/metabolism/pathology
TOR Serine-Threonine Kinases/metabolism
Membrane Potential, Mitochondrial

@article {pmid41026228,
year = {2025},
author = {Amemiya, S and Takao, H and Abe, O},
title = {Spatiotemporal patterns of amyloid deposition as prognostic markers of Alzheimer's disease.},
journal = {Neuroradiology},
volume = {},
number = {},
pages = {},
pmid = {41026228},
issn = {1432-1920},
abstract = {PURPOSE: The study aims to characterize the spatiotemporal distribution of amyloid deposition, differentiate between its subtypes, and explore their predictive value for patient cognitive outcomes.

METHODS: Amyloid PET data from a prospective consortium study, the Alzheimer's Disease Neuroimaging Initiative, were used. A spatial independent component analysis revealed regions of amyloid deposition covariation, which served as regions of interest. A subtype and stage inference analysis was then performed to infer spatiotemporal patterns from cross-sectional data. Multinomial logistic regression models evaluated the impacts of demographics and risk factors on subtype assignment and determined the prognostic value of the subtypes for cognitive decline. Longitudinal data were used for validation.

RESULTS: The study included 1,049 participants (466 cognitively normal, 447 mild cognitive impairment, and 136 Alzheimer's disease; 72 ± 8 years; 543 women), with follow-up data available for 643 (915 ± 431 days from baseline). Three distinct spatiotemporal patterns were identified, primarily affecting the parietal, frontotemporal, and occipital lobes, respectively, in the early stages. The amyloid deposition rates differed between the subtypes, even after age, diagnosis, apolipoprotein E ε4 carriership (APOE), baseline amyloid burden, and tracer types were controlled for (occipital vs. parietal: β = 32.6, P < .001; occipital vs. frontotemporal: β = 17.0, P = .017; parietal vs. frontotemporal: β = 15.6, P = .026). The rates of change in cognitive scores, adjusted for age, diagnosis, APOE, baseline amyloid burden, baseline cognitive score, and tracer types also differed between the subtypes (occipital vs. Stage 0: β = 0.162, P = .021; occipital vs. parietal: β = 0.134, P = .013).

CONCLUSION: Amyloid PET subtyping may serve as a valuable independent prognostic biomarker.},
}

@article {pmid41025909,
year = {2025},
author = {Sajimon, M and Wheeler, CJ and Foley, AR and Chan, K and Griffin, MN and Dinakarapandian, DM and Holberton, A and Joy, J and Paravastu, AK and Wood, LB and Raskatov, JA},
title = {Asparagine Deamidation Attenuates Toxicity, Aggregation, and Microglial Responses of Alzheimer's Amyloid-β.},
journal = {ACS chemical neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1021/acschemneuro.5c00544},
pmid = {41025909},
issn = {1948-7193},
abstract = {Alzheimer's disease (AD) is a growing global challenge that imposes a tremendous burden on society and economies. Though recently approved anti-amyloid β (Aβ) immunotherapies show effectiveness in clearing amyloid and slowing cognitive decline, the removal of cerebral Aβ can also cause serious adverse events (SAEs). Therefore, decreasing the detrimental effects of Aβ in the brain without promoting SAEs is an unmet need in AD treatment. Here, we show that deamidation of Asparagine 27(N27) in Aβ1-42 can significantly reduce Aβ's neurotoxicity and decrease selective microglial pro-inflammatory cytokine production. We also show that deamidation of N27 produces a pronounced decrease in Aβ's aggregation propensity and decreases soluble oligomer formation, suggesting a potential mechanism for its mitigation of Aβ's detrimental cellular effects. Modulation of these Aβ properties by N27 deamidation represents a proof of concept for a potential strategy to alter the detrimental effects of Aβ that may not require its removal from the brain. Our findings on reducing Aβ's toxic properties by N27 deamidation may provide a basis for future therapeutic interventions.},
}

@article {pmid41025716,
year = {2025},
author = {Ma, Y and Zhang, M and Jin, Y and Wang, Y and Ji, T and Wu, F and Li, Y and Wang, R and Guo, H and Ren, F and Fang, B},
title = {2'-Fucosyllactose Ameliorates Cognitive Impairment and Neuroinflammation in AD Mice.},
journal = {Journal of agricultural and food chemistry},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.jafc.5c06137},
pmid = {41025716},
issn = {1520-5118},
abstract = {2'-Fucosyllactose (2'-FL) supplementation is beneficial to brain function. Our previous study has already reported the prevention of AD by 2'-FL in mice; in this study, the effects of 2'-FL in AD were evaluated. Five month-old male 5 × FAD mice were gavaged with 2'-FL for 11 weeks, and 2 mg of 2'-FL significantly improved cognitive deficits, even restoring them to the normal level. The destroyed neurons, damaged synaptic plasticity characterized by decreased cholinergic neurons and glutaminergic neurons, and the activation of microglial cells were all significantly improved by 2'-FL. 2'-FL also significantly down-regulated mRNA expression of Il-6 and Il-1β and alleviated oxidative damages through the Keap1-Nrf2 pathway to up-regulate Nqo1 expression. AD-increased PC (18:4/20:5) and DG (18:4/22:6/0:0) in the feces and serum were both decreased by 2'-FL, which was significantly positively correlated with inflammation and negatively correlated with synaptic plasticity. This study lays a theoretical basis for the application of 2'-FL in neurodegenerative diseases.},
}

@article {pmid41025579,
year = {2025},
author = {He, F and He, H and Teng, C and Ren, C and Wang, L and Yang, Q and Li, H},
title = {Preliminary evidence for high-definition transcranial direct current stimulation effects on white matter microstructure and executive function in mild cognitive impairment.},
journal = {Neuroreport},
volume = {36},
number = {16},
pages = {967-975},
doi = {10.1097/WNR.0000000000002216},
pmid = {41025579},
issn = {1473-558X},
support = {2022KY02KJZ//This work was supported by Key Natural Science and Technology Project of Shaanxi Energy Institute/ ; },
mesh = {Humans ; *Cognitive Dysfunction/therapy/diagnostic imaging/physiopathology/pathology/psychology ; *Transcranial Direct Current Stimulation/methods ; Male ; Female ; *White Matter/diagnostic imaging/pathology ; Aged ; *Executive Function/physiology ; Diffusion Tensor Imaging ; Middle Aged ; Neuropsychological Tests ; Dorsolateral Prefrontal Cortex/diagnostic imaging ; Anisotropy ; Pyramidal Tracts/diagnostic imaging ; },
abstract = {BACKGROUND: Mild cognitive impairment (MCI) represents a critical window for intervention before Alzheimer's disease progression. This study investigated whether high-definition transcranial direct current stimulation (HD-tDCS) targeting the left dorsolateral prefrontal cortex (L-DLPFC) could modulate white matter microstructure and thereby influence cognitive function.

METHODS: Twenty-four patients with MCI received 10 sessions of active HD-tDCS over the L-DLPFC. White matter integrity was assessed using diffusion tensor imaging (DTI) to quantify fractional anisotropy in corticospinal tracts (CSTs) and anterior thalamic radiations (ATR). Cognitive function was evaluated with the trail making test B (TMT-B), mini-mental state examination (MMSE), and Montreal cognitive assessment (MoCA) at baseline and postintervention. Forty healthy controls provided baseline DTI data.

RESULTS: At baseline, patients with MCI showed significantly reduced fractional anisotropy in the bilateral CST and ATR compared with healthy controls. Following HD-tDCS, increases in fractional anisotropy were observed in these tracts. While MMSE and MoCA scores showed no significant change, TMT-B performance appeared to improve. Notably, increased fractional anisotropy in the left ATR showed an association with improved TMT-B performance (r = 0.467, P < 0.05).

CONCLUSION: The findings suggest that HD-tDCS targeting the L-DLPFC may promote microstructural remodeling in white matter tracts, evidenced by elevated fractional anisotropy within the corticospinal and anterior thalamic pathways. While global cognitive measures remained stable, a trend toward improved executive function (TMT-B) was observed, potentially associated with left ATR fractional anisotropy enhancement. This positions HD-tDCS as a candidate neuromodulatory intervention for MCI, warranting further investigation to confirm functional outcomes.},
}

Humans
*Cognitive Dysfunction/therapy/diagnostic imaging/physiopathology/pathology/psychology
*Transcranial Direct Current Stimulation/methods
Male
Female
*White Matter/diagnostic imaging/pathology
Aged
*Executive Function/physiology
Diffusion Tensor Imaging
Middle Aged
Neuropsychological Tests
Dorsolateral Prefrontal Cortex/diagnostic imaging
Anisotropy
Pyramidal Tracts/diagnostic imaging

@article {pmid41025578,
year = {2025},
author = {Zhang, C and Song, C and Li, X and Duan, Y and Liu, W and Lu, Z},
title = {Classification of mild cognitive impairment developmental trajectories using multispatial scale structural brain networks.},
journal = {Neuroreport},
volume = {36},
number = {16},
pages = {976-987},
doi = {10.1097/WNR.0000000000002218},
pmid = {41025578},
issn = {1473-558X},
mesh = {Humans ; *Cognitive Dysfunction/classification/diagnostic imaging/pathology ; Aged ; Male ; Female ; *Brain/pathology/diagnostic imaging ; Magnetic Resonance Imaging ; Alzheimer Disease/diagnostic imaging/pathology ; *Nerve Net/diagnostic imaging/pathology ; Aged, 80 and over ; },
abstract = {OBJECTIVE: In this study, we investigated the interactions between brain regions at different scales in patients with mild cognitive impairment (MCI) to classify patients with MCI who may develop Alzheimer's disease (MCI-Converter (MCI-c)) and those with stable cognitive states (MCI-Stable (MCI-s)) at multiple spatial scales.

METHODS: We divided the brain into 210, 40, and 12 regions, respectively, based on anatomical a priori, and then extracted six morphological features. Based on this, an intralayer structural brain network was constructed to detect connections between brain regions at different levels, and an interlayer network was constructed to explore connections between different spatial scales. Then these two networks were merged into a whole-brain network and trained the classifier after feature selection.

RESULTS: Our study successfully identified meaningful connectivity features for precise classification, achieving an accuracy of 92.41%. In addition, some frequently reported abnormal brain regions were localized to more precise regions.

CONCLUSION: The human brain is a complex system with multiple spatial and temporal scales and multiple levels, showing a large number of emergent phenomena. Understanding the hierarchical relationship between brain structure and function is crucial. The network we constructed is not only important for MCI classification, but also holds promise for investigating other neurological conditions and elucidating brain development processes. Limitations include that model training and evaluation used only the Alzheimer's Disease Neuroimaging Initiative cohort; independent cohort validation is required to confirm generalizability. Moreover, integration with other imaging modalities (e.g. functional MRI and PET) may further improve prediction and will be explored in future work.},
}

Humans
*Cognitive Dysfunction/classification/diagnostic imaging/pathology
Aged
Male
Female
*Brain/pathology/diagnostic imaging
Magnetic Resonance Imaging
Alzheimer Disease/diagnostic imaging/pathology
*Nerve Net/diagnostic imaging/pathology
Aged, 80 and over

@article {pmid41025536,
year = {2025},
author = {Lehrer, S and Rheinstein, PH},
title = {Structure-guided Docking of Benzene-1,3-Disulfonic Acid to the ApoE-HSPG Binding Site at Arginine 136 as a Christchurch-mimetic Therapeutic Strategy for Alzheimer Disease.},
journal = {Clinical neuropharmacology},
volume = {},
number = {},
pages = {},
doi = {10.1097/WNF.0000000000000649},
pmid = {41025536},
issn = {1537-162X},
abstract = {OBJECTIVES: The APOΕ3 Christchurch (APOΕ3Ch) variant, characterized by an R136S substitution, confers protection against Alzheimer disease (AD) by reducing apolipoprotein E (ApoE) binding to heparan sulfate proteoglycans (HSPGs), thereby limiting tau propagation. While antibody-based strategies mimicking this variant have shown promise, small-molecule approaches to disrupt the ApoE-HSPG interaction remain underexplored.

METHODS: We conducted a structure-guided molecular docking study targeting the ApoE HSPG-binding domain centered on Arg136, using AutoDock Vina within the SAMSON platform. The ligand benzene-1,3-disulfonic acid tiron, a small, anionic molecule with structural similarity to sulfated glycosaminoglycans, was docked to the cationic surface of ApoΕ3. Binding affinity, interaction pose, and root-mean-square deviation (RMSD) were assessed. Pharmacokinetic and toxicity predictions were performed using the pkCSM web server.

RESULTS: Benzene-1,3-disulfonic acid exhibited strong binding to the Arg136-containing pocket with a top docking score of -5.93 kcal/mol and an estimated inhibition constant (Ki) of 44.6 µmol. The top-ranked pose revealed stabilizing electrostatic interactions and hydrogen bonds with Arg136 and neighboring basic residues. pkCSM profiling predicted poor oral absorption and limited blood-brain barrier permeability, but a favorable safety profile, including no predicted hepatotoxicity, hERG inhibition (cardiac toxicity), or mutagenicity.

CONCLUSIONS: These findings establish the feasibility of targeting the ApoE-HSPG interface with small molecules and identify benzene-1,3-disulfonic acid as a candidate Christchurch mimetic. While pharmacokinetic limitations preclude systemic use, intranasal delivery or ligand optimization may overcome brain access barriers. This study provides a foundation for developing novel small-molecule therapeutics to disrupt ApoE-mediated tau pathology in AD.},
}

@article {pmid41025403,
year = {2025},
author = {Holloway, BM and Harding, CD and DeYoung, P and Kwan, CG and Avetisyan, L and Lui, KK and Ancoli-Israel, S and Banks, SJ and Djonlagic, I and Malhotra, A},
title = {Comorbid insomnia and sleep apnea (COMISA) is associated with worse verbal episodic memory in older women.},
journal = {Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine},
volume = {},
number = {},
pages = {},
doi = {10.5664/jcsm.11902},
pmid = {41025403},
issn = {1550-9397},
abstract = {STUDY OBJECTIVES: To investigate whether comorbid insomnia and sleep apnea (COMISA) is associated with poor verbal memory in older adults, and whether this relationship is moderated by sex.

METHODS: 110 older adults aged (65-83), all diagnosed with OSA, completed overnight polysomnography and cognitive testing. COMISA was defined as OSA plus an Insomnia Severity Index score ≥ 11. Verbal memory was assessed via the delayed recall component of the ADCS-PACC. Moderation analysis examined the interaction between COMISA and sex on verbal memory performance, adjusting for age, body mass index, APOE4 status, and education. Post hoc sleep architecture differences between men and women with COMISA and women with COMISA compared to OSA only were analyzed using MANCOVA.

RESULTS: COMISA was associated with significantly worse verbal memory performance, with this effect driven by women (b=-2.82, SE=0.94, t=-3.01, p=0.003) and absent in men (b=0.62, SE=0.97, t=0.63, p=0.528). Post hoc analyses revealed that women with COMISA showed reduced REM sleep and increased SWS compared to men with COMISA.

CONCLUSIONS: COMISA is linked to sex-specific cognitive vulnerability, with older women showing worse verbal memory than men. Post hoc analyses revealed differences in sleep architecture by sex within COMISA, warranting further investigation into stage-specific sleep contributions to cognitive risk. These findings highlight the importance of sex-informed approaches to assessing and managing cognitive risk in aging populations.

CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Is Obstructive Sleep Apnea Important in the Development of Alzheimer's Disease?; Identifier: NCT05094271; URL: https://clinicaltrials.gov/study/NCT05094271.},
}

@article {pmid41025379,
year = {2025},
author = {Eratne, D and Kang, M and Malpas, CB and Dang, C and Lewis, C and Bhalala, OG and Li, QX and Collins, S and Masters, CL and Loi, SM and Santillo, AF and Blennow, K and Zetterberg, H and Velakoulis, D and , },
title = {Plasma p-tau217, NfL, GFAP diagnostic performance and biomarker profiles in Alzheimer's disease, frontotemporal dementia, and psychiatric disorders, in a prospective unselected neuropsychiatry memory clinic.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21},
number = {10},
pages = {e70717},
doi = {10.1002/alz.70717},
pmid = {41025379},
issn = {1552-5279},
support = {2017-00915//Swedish Research/ ; 2022-00732//Swedish Research/ ; AF-930351//Swedish Alzheimer Foundation/ ; AF-939721//Swedish Alzheimer Foundation/ ; AF-968270//Swedish Alzheimer Foundation/ ; AF-994551//Swedish Alzheimer Foundation/ ; ALZ2022-0006//Hjärnfonden, Sweden/ ; FO2024-0048-TK-130//Hjärnfonden, Sweden/ ; FO2024-0048-HK-24//Hjärnfonden, Sweden/ ; ALFGBG-965240//ALF agreement/ ; ALFGBG-1006418//ALF agreement/ ; JPND2019-466-236//European Union Joint Programme for Neurodegenerative Disorders/ ; ZEN-21-848495//Alzheimer's Association 2021 Zenith Award/ ; SG-23-1038904 QC//Alzheimer's Association 2022-2025/ ; 2023-00356//the Swedish Research Council/ ; 2022-01018//the Swedish Research Council/ ; 2019-02397//the Swedish Research Council/ ; 101053962//European Union's Horizon Europe/ ; ALFGBG-71320//Swedish State Support for Clinical Research/ ; 201809-2016862//Alzheimer Drug Discovery Foundation (ADDF)/ ; ADSF-21-831376-C//AD Strategic Fund and the Alzheimer's Association/ ; ADSF-21-831381-C//AD Strategic Fund and the Alzheimer's Association/ ; ADSF-21-831377-C//AD Strategic Fund and the Alzheimer's Association/ ; ADSF-24-1284328-C//AD Strategic Fund and the Alzheimer's Association/ ; //European Union's Horizon Europe Research and Innovation Programme/ ; 22HLT07//NEuroBioStand/ ; FO2022-0270//Erling-Persson Family Foundation/ ; 860197//European Union's Horizon 2020/ ; JPND2021-00694//European Union Joint Programme-Neurodegenerative Disease Research/ ; UKDRI-1003//UK Dementia Research Institute/ ; ALF 2022 YF 0017//AFS/ ; },
mesh = {Humans ; *Alzheimer Disease/blood/diagnosis ; *tau Proteins/blood ; Female ; Male ; Biomarkers/blood ; *Frontotemporal Dementia/blood/diagnosis ; *Glial Fibrillary Acidic Protein/blood ; *Neurofilament Proteins/blood ; Aged ; Prospective Studies ; Middle Aged ; *Mental Disorders/blood/diagnosis ; Aged, 80 and over ; },
abstract = {INTRODUCTION: Plasma biomarkers offer promise for improving the diagnosis of Alzheimer's disease (AD) and differentiating AD and other neurodegenerative disorders (NDs) like frontotemporal dementia (FTD) from primary psychiatric disorders (PPDs), particularly in younger patients.

METHODS: In this prospective study, we investigated plasma phosphorylated tau 217 (p-tau217), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) in 341 unselected participants from a neuropsychiatry memory clinic, including AD (n = 40), behavioral variant FTD (bvFTD) (n = 15), PPD (n = 69), other NDs, and controls.

RESULTS: Plasma p-tau217 showed strong diagnostic performance for distinguishing AD from bvFTD (96% accuracy) and PPD (93% accuracy). NfL best distinguished all NDs from PPD, while GFAP did not bring additional value. Biomarker profiles using predefined cut-offs and age-adjusted z-scores further clarified group differences.

DISCUSSION: Plasma p-tau217 and NfL have strong diagnostic utility in real-world, diagnostically complex cohorts. These findings support implementation of scalable blood-based biomarkers to improve early and accurate diagnosis in memory clinical settings.

HIGHLIGHTS: Plasma p-tau217 was significantly elevated in AD compared to other disorders. P-tau217 distinguished AD from bvFTD with high accuracy. P-tau217 distinguished AD from PPDs with high accuracy. NfL/p-tau217 ratio and GFAP added limited diagnostic value compared to p-tau217 and NfL. Findings support blood biomarkers in younger, real-world clinical cohorts.},
}

Humans
*Alzheimer Disease/blood/diagnosis
*tau Proteins/blood
Female
Male
Biomarkers/blood
*Frontotemporal Dementia/blood/diagnosis
*Glial Fibrillary Acidic Protein/blood
*Neurofilament Proteins/blood
Aged
Prospective Studies
Middle Aged
*Mental Disorders/blood/diagnosis
Aged, 80 and over

@article {pmid41025328,
year = {2025},
author = {Barber, D and Hasselmo, ME and Rice, HC},
title = {Modeling presynaptic inhibition by the amyloid precursor protein demonstrates one potential mechanism for preventing runaway synaptic modification in Alzheimer's disease.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21},
number = {10},
pages = {e70748},
doi = {10.1002/alz.70748},
pmid = {41025328},
issn = {1552-5279},
mesh = {*Alzheimer Disease/metabolism/physiopathology ; Humans ; *Amyloid beta-Protein Precursor/metabolism ; *Synapses/physiology ; Computer Simulation ; *Models, Neurological ; Receptors, GABA-B/metabolism ; *Presynaptic Terminals ; Long-Term Potentiation/physiology ; },
abstract = {INTRODUCTION: Previous simulations of Hebbian associative memory models inspired the malignant synaptic growth hypothesis of Alzheimer's disease (AD), which suggests that cognitive impairments arise due to runaway synaptic modification resulting from poor separation between encoding and retrieval.

METHODS: We computationally model presynaptic inhibition by the recently identified interaction of soluble amyloid precursor protein alpha (sAPPα) with γ-aminobutyric acid type B receptor (GABABR) as one potential biological mechanism that can enhance separation between encoding and retrieval.

RESULTS: Simulations predict that the dual effect of sAPPα on long-term potentiation and presynaptic inhibition of glutamatergic synapses maintains effective associative memory function and prevents runaway synaptic modification. Moreover, computational modeling predicts that sAPPα, which interacts with the 1a isoform of GABABR, is more effective than the GABABR agonist baclofen at stabilizing associative memory.

DISCUSSION: Molecular mechanisms that enhance presynaptic inhibition, such as sAPPα-GABABR1a signaling, are potential therapeutic targets for preventing cognitive impairments in AD.

HIGHLIGHTS: Computational modeling of Hebbian associative memory provides a framework for understanding the functional basis of Alzheimer's disease. Soluble amyloid precursor protein (sAPPα) presynaptic activation of γ-aminobutyric acid B (GABAB) receptors prevents runaway synaptic modification in associative memory models. sAPPα is more effective than baclofen at stabilizing associative memory.},
}

*Alzheimer Disease/metabolism/physiopathology
Humans
*Amyloid beta-Protein Precursor/metabolism
*Synapses/physiology
Computer Simulation
*Models, Neurological
Receptors, GABA-B/metabolism
*Presynaptic Terminals
Long-Term Potentiation/physiology

@article {pmid41025225,
year = {2025},
author = {Verberk, IMW and Gouda, M and Antwi-Berko, D and van Leeuwenstijn, M and Bongers, B and Houtkamp, IM and van der Flier, WM and Janelidze, S and Hansson, O and Bastard, NL and Vandijck, M and Hunter, J and Honigberg, L and Kirmess, KM and Verghese, PB and Blennow, K and Zetterberg, H and Meyers, EA and Edelmayer, RM and Teunissen, C},
title = {Evidence-based standardized sample handling protocol for accurate blood-based Alzheimer's disease biomarker measurement: Results and consensus of the Global Biomarker Standardization Consortium.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21},
number = {10},
pages = {e70752},
doi = {10.1002/alz.70752},
pmid = {41025225},
issn = {1552-5279},
support = {//research grants of Health Holland and ZonMW/ ; //Pasman Stichting. Research of Alzheimer Center Amsterdam/ ; //Stichting Alzheimer Nederland and Stichting Steun Alzheimercentrum Amsterdam/ ; 2017-00915//Swedish Research Council/ ; 2022-00732//Swedish Research Council/ ; AF-930351//Swedish Alzheimer Foundation/ ; AF-939721//Swedish Alzheimer Foundation/ ; AF-968270//Swedish Alzheimer Foundation/ ; AF-994551//Swedish Alzheimer Foundation/ ; ALZ2022-0006//Hjärnfonden, Sweden/ ; FO2024-0048-TK-130//Hjärnfonden, Sweden/ ; FO2024-0048-HK-24//Hjärnfonden, Sweden/ ; //European Union Joint Program for Neurodegenerative Disorders/ ; //Alzheimer's Association 2021 Zenith Award/ ; //La Fondation Recherche Alzheimer (FRA)/ ; //Kirsten and Freddy Johansen Foundation/ ; //Swedish State Support for Clinical Research/ ; ADSF-21-831376-C//AD Strategic Fund and the Alzheimer's Association/ ; ADSF-21-831381-C//AD Strategic Fund and the Alzheimer's Association/ ; ADSF-21-831377-C//AD Strategic Fund and the Alzheimer's Association/ ; ADSF-24-1284328-C//AD Strategic Fund and the Alzheimer's Association/ ; //the European Partnership on Metrology/ ; //Cure Alzheimer's Fund/ ; //Olav Thon Foundation, the Erling-Persson Family Foundation/ ; //Familjen Rönströms Stiftelse/ ; //Familjen Beiglers Stiftelse/ ; //Stiftelsen för Gamla Tjänarinnor/ ; 860197//Marie Skłodowska-Curie/ ; JPND2021-00694//European Union Joint Programme - Neurodegenerative Disease Research/ ; //National Institute for Health and Care Research University College London Hospitals Biomedical Research Centre/ ; 860197 (MIRIADE//European Commission (Marie Curie International Training Network/ ; 101119596//European Commission (Marie Curie International Training Network/ ; //Innovative Medicines Initiatives 3TR/ ; //(bPRIDE, CCAD), European Partnership on Metrology/ ; 101053962//European Union's Horizon Europe Research and Innovation Programme/ ; 101053962//European Union's Horizon Europe Research and Innovation Programme/ ; 201809-2016862//the Alzheimer Drug Discovery Foundation/ ; //Michael J. Fox Foundation/ ; //Health Holland, the Dutch Research Council (ZonMW)/ ; //Alzheimer Drug Discovery Foundation/ ; //Selfridges Group Foundation/ ; //Alzheimer Netherlands/ ; //Health Holland/ ; LSHM20106//Topsector Life Sciences & Health/ ; //Dutch National Dementia Strategy/ ; },
mesh = {*Alzheimer Disease/blood/diagnosis ; Humans ; *Biomarkers/blood ; Amyloid beta-Peptides/blood ; tau Proteins/blood ; Glial Fibrillary Acidic Protein/blood ; *Specimen Handling/standards/methods ; Neurofilament Proteins/blood ; Peptide Fragments/blood ; *Blood Specimen Collection/standards/methods ; Consensus ; },
abstract = {INTRODUCTION: Blood-based biomarkers (BBMs) have revolutionized Alzheimer's disease diagnosis and monitoring. Their pre-analytical stability requires scrutiny. This study assessed pre-analytical effects to inform a standardized sample handling protocol.

METHODS: Assessed pre-analytical variations included collection tube type, hemolysis, centrifugation settings, centrifugation/storage delays, tube transfers, and freeze-thawing (n = 15/experiment). Phosphorylated tau (pTau) isoforms were measured with Simoa, Lumipulse, MesoScale Discovery, and immunoprecipitation-mass spectrometry. Amyloid-beta (Aβ42, Aβ40), glial fibrillary acidic protein (GFAP), and neurofilament light (NfL) protein were measured with Simoa.

RESULTS: All assessed BBM levels varied by over 10% by collection tube type. Aβ peptides were the most sensitive, and their levels declined >by more than 10% under storage and centrifugation delays, more steeply at room temperature (RT) compared with 2°C to 8°C. NfL and GFAP levels increased by more than 10% upon RT/-20°C storage. pTau isoforms demonstrated stability across most pre-analytical variations.

DISCUSSION: We established an evidence-based handling protocol to ensure reliable sample handling for neurological BBMs upon adoption in clinics, trials, and research.

HIGHLIGHTS: Sample handling protocols can mitigate pre-analytical effects on BBM results. We developed an evidence-based, expert-consensus plasma sample handling protocol. Primary collection tube and delays to centrifuging or freezing impact AD BBMs. Plasma pTau217 is highly resistant to pre-analytical sample handling variations. Plasma Aβ42 and Aβ40 were most sensitive to pre-analytical variations.},
}

*Alzheimer Disease/blood/diagnosis
Humans
*Biomarkers/blood
Amyloid beta-Peptides/blood
tau Proteins/blood
Glial Fibrillary Acidic Protein/blood
*Specimen Handling/standards/methods
Neurofilament Proteins/blood
Peptide Fragments/blood
*Blood Specimen Collection/standards/methods
Consensus

@article {pmid41025221,
year = {2025},
author = {Ouellette, A and O'Connell, K and Kaczorowski, C},
title = {Evaluation of hippocampal DLGAP2 overexpression on cognition, synaptic function, and dendritic spine structure in a translationally relevant AD mouse model.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21},
number = {10},
pages = {e70728},
doi = {10.1002/alz.70728},
pmid = {41025221},
issn = {1552-5279},
support = {F31AG077860-01A1/AG/NIA NIH HHS/United States ; RF1AG063755/AG/NIA NIH HHS/United States ; RF1AG059778/AG/NIA NIH HHS/United States ; T32 GM132006/GM/NIGMS NIH HHS/United States ; },
mesh = {Animals ; *Hippocampus/metabolism/pathology ; *Dendritic Spines/pathology/metabolism ; *Alzheimer Disease/pathology/genetics/metabolism ; Disease Models, Animal ; Mice, Transgenic ; Mice ; *Synapses/pathology ; *Cognition/physiology ; Neuronal Plasticity/physiology ; *GTPase-Activating Proteins/metabolism/genetics ; Male ; Humans ; },
abstract = {INTRODUCTION: Developing effective therapeutics for Alzheimer's disease (AD) requires a better understanding of the molecular drivers of the disease. Our previous work nominated DLGAP2 as a modifier of age-related cognitive decline and risk for AD. We tested the hypothesis that overexpression of DLGAP2 in the hippocampus would protect against cognitive and synaptic deficits in a susceptible F1 5XFAD model.

METHODS: DLGAP2 was overexpressed in the hippocampus of F1 hybrid 5XFAD and non-transgenic littermates using a viral approach. Cognitive function, electrophysiological properties, and dendritic spine morphology were assessed at 6 and 14 months of age.

RESULTS: DLGAP2 overexpression impaired synaptic plasticity and exacerbated AD-related memory deficits but had minimal effect on spine structure or intrinsic neuronal properties.

DISCUSSION: We highlight the complex role of DLGAP2 in AD pathology. Targeted interventions involving postsynaptic proteins must consider potential adverse effects on synaptic integrity and cognitive performance, particularly in the context of AD.

HIGHLIGHTS: DLGAP2 overexpression accelerates AD-related impairment of contextual fear acquisition and memory. DLGAP2 overexpression impairs synaptic plasticity prior to AD-related memory impairment, but not intrinsic excitability. Effect of DLGAP2 overexpression on thin spine density was blunted in AD mice from in vivo dendritic spine results that were replicated in cultured rodent neurons.},
}

Animals
*Hippocampus/metabolism/pathology
*Dendritic Spines/pathology/metabolism
*Alzheimer Disease/pathology/genetics/metabolism
Disease Models, Animal
Mice, Transgenic
Mice
*Synapses/pathology
*Cognition/physiology
Neuronal Plasticity/physiology
*GTPase-Activating Proteins/metabolism/genetics
Male
Humans

@article {pmid41025082,
year = {2025},
author = {Park, J and Montero-Hernandez, S and Huff, AJ and Lee, C and Pollonini, L and Park, L and Lin, L and Telkes, I and Galvin, JE and Hoang, J and Ahn, H},
title = {Advancing pain assessment in Alzheimer's disease and related dementias: Functional near-infrared spectroscopy for investigating brain activity.},
journal = {British journal of pain},
volume = {},
number = {},
pages = {20494637251384009},
pmid = {41025082},
issn = {2049-4637},
abstract = {BACKGROUND: Pain assessment in Alzheimer's disease and related dementias (ADRD) is challenging due to cognitive decline and communication barriers, limiting the reliability of self-report and observational tools. Functional near-infrared spectroscopy (fNIRS) offers a noninvasive measure of cerebral hemodynamic responses and may serve as an objective biomarker for pain. This pilot study evaluated the feasibility of fNIRS for pain assessment in ADRD, using transcranial direct current stimulation (tDCS) solely as a controlled cortical modulation paradigm to test fNIRS sensitivity, rather than as a therapeutic intervention.

METHODS: Forty older adults with mild to moderate ADRD were randomized to active (n = 20) or sham (n = 20) tDCS for 5 consecutive days to generate controlled cortical modulation. Pain was assessed using the Numerical Rating Scale (NRS), Mobilization-Observation-Behavior-Intensity-Dementia-2 (MOBID-2), and fNIRS responses to standardized pain stimuli. Hemodynamic changes in prefrontal and somatosensory cortices were analyzed to determine whether fNIRS detected pain-related brain activity.

RESULTS: NRS and MOBID-2 scores were significantly correlated at baseline (r = .605, p < .001) and post-intervention (r = .567, p < .001). In the active tDCS condition, pain stimulation elicited significant cortical hemodynamic changes that correlated with pain scores (p < .05), supporting fNIRS's sensitivity for detecting pain-related neural responses. In the sham group, only a few significant correlations were observed post-intervention (e.g., frontal cortex r = .44, p = .049; prefrontal cortex r = .52, p = .017), which were less consistent compared to the active condition.

CONCLUSION: fNIRS demonstrated feasibility as an objective pain assessment tool in ADRD. tDCS served only as a probe to induce cortical modulation for evaluating fNIRS performance. In this study, tDCS functioned as a probe to induce cortical modulation for evaluating fNIRS sensitivity, not as a therapeutic intervention. Larger trials are needed to confirm fNIRS validity for clinical application.},
}

@article {pmid41025042,
year = {2025},
author = {Huang, DH and Zhang, YL and Shi, SL and Liang, TJ and Chen, JJ and Li, GQ and Chen, ZD},
title = {Mendelian Randomization Analysis of the Relationship Between Immune-Related Diseases and Alzheimer's Disease.},
journal = {Journal of multidisciplinary healthcare},
volume = {18},
number = {},
pages = {6063-6077},
pmid = {41025042},
issn = {1178-2390},
abstract = {OBJECTIVE: Emerging evidence suggests a genetic link between immune-related diseases and Alzheimer's disease (AD), though the underlying mechanisms remain unclear. This Mendelian randomization (MR) study investigates the genetic relationship between six immune-related diseases-type 1 diabetes (T1DM), systemic lupus erythematosus (SLE), asthma, myasthenia gravis (MG), endometriosis, and idiopathic thrombocytopenic purpura (ITP)-and AD.

METHODS: Summary-level data were obtained from publicly available genome-wide association studies (GWAS) for the six immune-related diseases and AD. MR-estimation was conducted utilizing the inverse variance weighted (IVW), MR-Egger, and WM methods. Additionally, sensitivity analyses were performed, encompassing Cochran's Q test, MR-Egger intercept, MR-Pleiotropy residual sum and outlier (MR-PRESSO) method, leave-one-out analysis, and funnel plots.

RESULTS: A statistically significant association was identified between asthma and a slightly lower risk of AD (odds ratio [OR] = 0.996, 95% CI: 0.994-0.997, P = 0.001); however, the effect size was negligible and likely lacks clinical significance. No significant genetic associations were found between T1DM, SLE, MG, endometriosis, or ITP and AD. Reverse MR analyses indicated no evidence of reverse causality from AD to these immune-related conditions.

CONCLUSION: Although a nominal association was observed, this MR analysis does not support a causal relationship between genetic liability to asthma and Alzheimer's disease. This relationship underscores the specificity of the association, as no causal connections were found between other studied immune-related diseases conditions-T1DM, SLE, MG, endometriosis, and ITP-and AD.},
}

@article {pmid41024939,
year = {2024},
author = {Saleh, AY and Valentina, R and Susanto, TD and Saputra, DAY},
title = {Beyond stroke therapy, neuroaid (a chinese herbal) has an effect on cognition and neurogenesis, a bibliometric study.},
journal = {F1000Research},
volume = {13},
number = {},
pages = {799},
doi = {10.12688/f1000research.152581.2},
pmid = {41024939},
issn = {2046-1402},
mesh = {Humans ; *Drugs, Chinese Herbal/therapeutic use/pharmacology ; *Cognition/drug effects ; *Stroke/drug therapy ; Bibliometrics ; *Neurogenesis/drug effects ; Animals ; },
abstract = {INTRODUCTION: NeuroAiD, also known as MLC601 or MLC901, is a Chinese herbal combination used worldwide for stroke treatment. It contains herbal components and five hewan components. MLC601 contains herbal components and hewan components, while MLC901 has a similar herbal composition. NeuroAiD is used to support neurologic recovery after stroke and to aid cognitive function in Alzheimer's disease. Studies show that NeuroAiD has potential in treating Alzheimer's disease and is beneficial in both local and global stroke models and in the Kortikal culture. However, there is limited bibliometric research on NeuroAiD, which is a method of collecting data from published articles to analyze developments and trends in the field of research. This research contributes significantly to the literature and helps develop more effective stroke treatment strategies.

METHODS: In this work, a literature review methodology is employed to gather data from the Scopus database using the keywords neuroaid. Data were analyzed using Biblioshiny and VOSviewer software to produce visualizations and bibliometric maps. We conducted quantitative and qualitative analysis.

RESULTS: The research trend found are documents by year, most relevant sources, factorial map of the most cited documents, factorial map of The documents with the highest contributes, documents by author, documents by country or territory, documents by subject area, documents by affiliation, network visualization, overlay visualization of scopus database using vosviewer, density visualization, thematic map, thematic evolution, topic dendogram, and world cloud.

CONCLUSIONS: The study investigates the potential of Neuroaid, a neuroprotective drug, for stroke prevention and cognitive function enhancement. It uses terms like "cognition" and "neurogenesis" to highlight its potential. While the study's focus may be limited, it provides valuable insights into research direction and potential areas of neuroaid for stroke treatment.},
}

Humans
*Drugs, Chinese Herbal/therapeutic use/pharmacology
*Cognition/drug effects
*Stroke/drug therapy
Bibliometrics
*Neurogenesis/drug effects
Animals

@article {pmid41024926,
year = {2025},
author = {Bitar, I and Alabdalrazzak, M and Zamzam, M and Desai, Y and Abushaban, K},
title = {Clinically Silent Amyloid-Related Imaging Abnormality With Edema Following Lecanemab Therapy: A Case Report.},
journal = {Cureus},
volume = {17},
number = {8},
pages = {e91230},
pmid = {41024926},
issn = {2168-8184},
abstract = {Amyloid-related imaging abnormalities with edema (ARIA-E) are a known complication of anti-amyloid monoclonal antibody therapies such as lecanemab. ARIA-E represents vasogenic cerebral edema resulting from treatment-related disruption of vascular amyloid and appears on MRI as cortical or gyriform T2 fluid-attenuated inversion recovery (FLAIR) hyperintensities. Clinically, ARIA-E ranges from asymptomatic radiologic findings to symptomatic events such as headache, confusion, or seizures, making routine surveillance important during therapy. We present the case of a 60-year-old woman with biomarker-confirmed AD who developed radiographically evident ARIA-E following six biweekly infusions of lecanemab. Surveillance MRI revealed new cortically based and gyriform T2 FLAIR hyperintensities in the posterior occipital and bilateral temporal lobes, consistent with parenchymal and sulcal edema. Notably, the patient remained neurologically asymptomatic throughout the episode. Lecanemab therapy was discontinued, and she was managed conservatively with close outpatient follow-up. This case highlights the importance of routine imaging during anti-amyloid therapy and demonstrates that conservative management may be appropriate in select asymptomatic cases of ARIA-E.},
}

@article {pmid41024900,
year = {2025},
author = {Yoshiwara, J and Yamamoto, N and Kasai, K and Ohta, R},
title = {Hidden Contribution of Severe Gastroesophageal Reflux Disease to Recurrent Pneumonia in an Octogenarian With Prior Gastrectomy.},
journal = {Cureus},
volume = {17},
number = {8},
pages = {e91250},
pmid = {41024900},
issn = {2168-8184},
abstract = {We report the case of an 88-year-old man with a history of distal gastrectomy who developed recurrent episodes of pneumonia within short intervals despite appropriate antibiotic therapy. He presented with fever and increased sputum production only two days after discharge from a prior pneumonia admission. His medical history included Alzheimer's disease, dilated cardiomyopathy, type 2 diabetes mellitus, and permanent atrial fibrillation. On admission, he was febrile and hypoxemic, with fine crackles on chest auscultation and new infiltrates on radiography and computed tomography. Despite the absence of overt swallowing dysfunction, the repeated recurrence prompted further evaluation. Upper gastrointestinal endoscopy revealed persistent Los Angeles grade C gastroesophageal reflux disease (GERD) despite proton pump inhibitor therapy. The patient also reported lying down immediately after meals, suggesting nocturnal and postprandial microaspiration as a key mechanism. Antibiotic therapy with ceftriaxone improved the pulmonary infiltrates, and he was discharged with reinforced reflux precautions and continued acid suppression therapy. Following discharge, he adhered to these lifestyle modifications and has not required readmission for pneumonia. This case highlights GERD as an underrecognized cause of recurrent pneumonia in elderly patients without obvious dysphagia. A comprehensive evaluation for GERD is crucial in managing unexplained recurrent pneumonia, particularly in patients with dementia, prior gastric surgery, or other aspiration risk factors.},
}

@article {pmid41024723,
year = {2025},
author = {Chen, J and Yu, S and Xie, G and Feng, R and Cui, W and Cai, R and Tang, K and Zhang, N and Wu, YX},
title = {Construction of an endogenously activated nanoamplifier for high-sensitivity detection and multimodal bioimaging of Alzheimer's disease.},
journal = {The Analyst},
volume = {},
number = {},
pages = {},
doi = {10.1039/d5an00544b},
pmid = {41024723},
issn = {1364-5528},
abstract = {Based on DNA hairpin structures, MnO2 nanoflowers, and Tf-AuNCs, an endogenously-activated Tf-AuNC-DNA@MnO2 multifunctional nanoamplifier was developed for the sensitive detection of microRNA-9 (miR-9) and efficient multimodal bioimaging in living HT-22 cells and brain tissues by two-photon near-infrared fluorescence imaging (TP-NIRFI), fluorescence lifetime imaging (FLIM), and magnetic resonance imaging (MRI). The Tf-AuNC-DNA@MnO2 multifunctional nanoamplifier exhibits superior two-photon near-infrared (TP-NIR) properties and extended fluorescence lifetimes. Using an enzyme-free amplification technique, i.e., the hybridization chain reaction (HCR), this approach can detect miR-9 with high selectivity and sensitivity and a low limit of detection (LOD) of 396 pM. In the brain tissue of AD mice, TP-NIRFI achieved a penetration depth of 290 μm and enabled a clear distinction between wild-type and APP/PS1 transgenic mice. Moreover, MRI could monitor H2O2 that induced the activation of the multifunctional nanoamplifier in real time. More importantly, the Tf-AuNC-DNA@MnO2 multifunctional nanoamplifier could monitor in real-time the dynamic changes of endogenous miR-9 induced by Aβ oligomers in HT-22 cells with multimodal imaging technology. Therefore, the Tf-AuNC-DNA@MnO2 multifunctional nanoamplifier can provide a comprehensive and in-depth understanding of the occurrence and development of AD, offering a new method and a powerful tool for early diagnosis of the disease.},
}

@article {pmid41024716,
year = {2025},
author = {Persson, K and Rhodius-Meester, HFM and Edwin, TH and Knapskog, AB and Bekkhus-Wetterberg, P and Selbæk, G and Engedal, K and Schellhorn, T},
title = {Automatic MRI Volumetry Assisted Visual Assessment of the Medial Temporal Lobe in Clinical Dementia Work-Up.},
journal = {Brain and behavior},
volume = {15},
number = {10},
pages = {e70948},
doi = {10.1002/brb3.70948},
pmid = {41024716},
issn = {2162-3279},
support = {//KLINBEFORSK/ ; //Alzheimer Nederland/ ; //Memorabel Dementia Fellowship 2021/ ; //Horizon 2022/ ; //Nasjonalforeningen for Folkehelsen/ ; //The Southern and Eastern Norway Regional Health Authority/ ; },
mesh = {Humans ; Female ; Male ; Aged ; *Temporal Lobe/pathology/diagnostic imaging ; *Magnetic Resonance Imaging/methods ; *Dementia/diagnostic imaging/pathology/diagnosis ; *Cognitive Dysfunction/diagnostic imaging/pathology/diagnosis ; Middle Aged ; Alzheimer Disease/diagnostic imaging/pathology ; Atrophy/pathology ; Aged, 80 and over ; Hippocampus/pathology/diagnostic imaging ; },
abstract = {INTRODUCTION: Efficient and cost-effective diagnostic tools for supporting dementia assessment are increasingly important. We aimed to evaluate whether providing neuroradiologists with volumetric data from an automatic MRI software, NeuroQuant, enhanced the diagnostic accuracy of their visual MRI assessment.

METHODS: Two neuroradiologists assessed brain MRIs from 366 patients (mean age 67.5 years, SD 9.2, and 52% females) with subjective cognitive decline (SCD, n 79), mild cognitive impairment (MCI, n 86), or dementia (n 201). The MCI and dementia patients were further diagnosed according to an etiology of Alzheimer's disease (AD, n 217) versus non-AD (n 70). In random order the neuroradiologists visually evaluated medial temporal lobe atrophy (MTA, scale 0-4) with and without having access to the NeuroQuant report of age and sex adjusted volumetric percentiles of the hippocampus. Receiver operating characteristics (ROCs) analyses were conducted to calculate the area under the curves (AUCs) for the visual MTA, the automated NeuroQuant percentile, and the combined NeuroQuant-assisted MTA in discriminating dementia from SCD and AD from non-AD.

RESULTS: The AUC of the visual MTA for dementia versus SCD discrimination increased slightly but not significantly when the neuroradiologists were provided with NeuroQuant results (AUC 0.76-0.79, p 0.28). Yet, the isolated NeuroQuant evaluation reached the highest accuracy (AUC 0.85, p < 0.001), significantly better than the MTA assessment (p 0.002) and the NeuroQuant-assisted MTA (p 0.04). Only the isolated NeuroQuant assessment discriminated AD from non-AD (AUC 0.60, p 0.006).

CONCLUSION: On the basis of our findings, we suggest an increased use of clinically approved automatic volumetry methods in radiological departments.},
}

Humans
Female
Male
Aged
*Temporal Lobe/pathology/diagnostic imaging
*Magnetic Resonance Imaging/methods
*Dementia/diagnostic imaging/pathology/diagnosis
*Cognitive Dysfunction/diagnostic imaging/pathology/diagnosis
Middle Aged
Alzheimer Disease/diagnostic imaging/pathology
Atrophy/pathology
Aged, 80 and over
Hippocampus/pathology/diagnostic imaging

@article {pmid41024673,
year = {2025},
author = {Masurkar, PP and Rikame, S},
title = {Gait assessment using wearable technologies in neurological disorders: a rapid umbrella.},
journal = {Neurodegenerative disease management},
volume = {},
number = {},
pages = {1-14},
doi = {10.1080/17582024.2025.2560775},
pmid = {41024673},
issn = {1758-2032},
abstract = {BACKGROUND: Gait analysis is essential tool for tracking neurological disorders-Parkinson's disease (PD), stroke, Alzheimer's disease (AD), and multiple sclerosis (MS). Wearable technologies enable continuous, noninvasive gait tracking beyond clinical settings but face challenges in accuracy and adoption. This review investigates wearable gait assessment, identifying patterns and future needs.

METHODS: This rapid umbrella review was conducted, synthesizing systematic reviews and meta-analyses of wearable technologies for gait assessment in PD, stroke, AD, and MS. Following PRISMA guidelines two reviewers screened, extracted data on gait outcomes, and assessed quality using AMSTAR-2.

RESULTS: Seventeen reviews (13systematic, 4meta-analyses) encompassing 308 primary studies were included. Most focused-on PD (n = 12), followed by stroke (n = 8), MS (n = 4), and AD (n = 2). Gait was primary outcome, alongside balance, fall risk, and mobility. Wearables (e.g. inertial sensors,) showed good diagnostic accuracy. Real-time biofeedback and exoskeletons improved function. Sensor placement differed greatly, usability was underreported.

CONCLUSIONS: Lack of standardization, validation, and usability limits clinical adoption. Future efforts must prioritize real-world testing and user-centered design.},
}

@article {pmid41024644,
year = {2025},
author = {Brazhnikov, M and Kusainova, T and Kopeykina, AS and Tarasova, IA},
title = {TMTCrunch: A Proteomic Atlas of Alternative Splicing for Predicting Splicing-Induced Implications in Aging and Alzheimer's Disease.},
journal = {Journal of proteome research},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.jproteome.5c00426},
pmid = {41024644},
issn = {1535-3907},
abstract = {Alzheimer's disease (AD) is the most prevalent form of dementia with incompletely understood pathogenesis. A major gap arises from the lack of proteomics tools capable of characterizing alternative splicing (AS)-derived proteoforms and their contributions to neurodegeneration. We developed a novel bioinformatics pipeline, TMTCrunch, tailored for rigorous quantitative meta-analysis of big proteomics data at the splice-proteoform level. TMTCrunch characterizes each proteoform by unique peptides, assessing similarity to canonical peptides and unique peptide coverage, employing SMD-based quantitation, and predicting proteoform-specific alterations of protein-protein interactions (PPIs) and novel post-translational modifications (PTMs) on spliced peptides. Applying TMTCrunch to 420 brain samples, we constructed the first atlas of splicing translatomes in AD, reproducibly identifying 870 noncanonical proteoforms. Differential analysis suggests splicing affecting proteoforms implicated in cytoskeletal regulation (e.g., MAPT, CLU, DPYSL3, ACTN2, SORBS1, FHL1), glutamatergic transmission (GRIA3), pre-mRNA splicing regulation (ARL6IP4), potassium channel modulation (DPP6), and cAMP signaling (PDE4D). Our analysis predicts disruption of PPIs within the Rho GTPase and EGFR signaling pathways and PTMs (deamidation, oxidation, phosphorylation) within AS regions, regardless of disease state. This approach implicates specific proteoforms in neurodegeneration: DPP6 (P42658-2), GRIA3 (P42263-2), the three-repeat isoforms of tau (3R-MAPT), and ASPH (Q12797-7). This study provides new insights into linking splicing to neurodegeneration.},
}

@article {pmid41024641,
year = {2025},
author = {Wilkins, J and Neira, CM and Su, L and , },
title = {Baseline Impaired Insight Predicts Longitudinal Brain Atrophy in Alzheimer's Disease and Related Cognitive States: A 30-Month Cohort Study From the ADNI Dataset.},
journal = {Brain and behavior},
volume = {15},
number = {10},
pages = {e70893},
doi = {10.1002/brb3.70893},
pmid = {41024641},
issn = {2162-3279},
support = {(NIHR203321 to C.M.N. and L.S.)//the Sheffield NIHR Biomedical Research Centre/ ; (ARUK-SRF2017B-1 to L.S.)//Alzheimer's Research UK Senior Research Fellowship/ ; //the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904)/ ; //DOD ADNI (Department of Defense award number W81XWH-12-2-0012)/ ; },
mesh = {Humans ; *Alzheimer Disease/pathology/psychology ; Atrophy/pathology ; Male ; Aged ; Female ; *Cognitive Dysfunction/pathology/psychology ; *Brain/pathology ; Longitudinal Studies ; Disease Progression ; Aged, 80 and over ; Magnetic Resonance Imaging ; Cohort Studies ; Cognition/physiology ; Gray Matter/pathology ; Neuroimaging ; },
abstract = {BACKGROUND: Impaired insight can be understood clinically as a loss of ability to appropriately recognize one's own disease status. Investigating insight in Alzheimer's disease (AD) and its relation to longitudinal changes in brain structure is important to understand the disease progression.

OBJECTIVE: To examine how the character of insight changes with disease stage and assess whether baseline levels of impaired insight can predict rate of brain atrophy across a period of 30 months in a cohort of subjects consisting of subjective memory complaint (SMC), mild cognitive impairment (MCI), AD, and cognitively normal (CN) controls.

METHODS: Data from 794 eligible participants were extracted from the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset. Insight levels were estimated by the Measurement of Everyday Cognition (ECog). Impairment was further categorized into overestimation or underestimation of ability. Brain atrophy rates were estimated by measuring change in gray matter volume within 30 months.

RESULTS: Overestimating ability was significantly correlated with increased whole-brain atrophy rates (p < 0.001) independent of general cognitive decline. Overestimation of ability exhibited significant correlations with increased atrophy in specific regions of the brain including the medial temporal lobe, fusiform gyrus, and hippocampus.

DISCUSSION: The present results suggest a statistically significant correlation between overestimation of ability and increased rates of subsequent brain atrophy. This is particularly notable in regions of the brain such as the hippocampus. However, further study into the phenomenon of insight and its progression over the disease course is required before its potential clinical utility can be fully assessed.},
}

Humans
*Alzheimer Disease/pathology/psychology
Atrophy/pathology
Male
Aged
Female
*Cognitive Dysfunction/pathology/psychology
*Brain/pathology
Longitudinal Studies
Disease Progression
Aged, 80 and over
Magnetic Resonance Imaging
Cohort Studies
Cognition/physiology
Gray Matter/pathology
Neuroimaging

@article {pmid41024640,
year = {2025},
author = {Varma, T and Kamble, P and Garg, P},
title = {Rational Discovery of BACE1-Selective Inhibitors as Potential Therapeutics for Alzheimer's Disease.},
journal = {Drug development research},
volume = {86},
number = {7},
pages = {e70169},
doi = {10.1002/ddr.70169},
pmid = {41024640},
issn = {1098-2299},
support = {//The authors received no specific funding for this work./ ; },
mesh = {*Amyloid Precursor Protein Secretases/antagonists & inhibitors/metabolism ; *Alzheimer Disease/drug therapy ; *Aspartic Acid Endopeptidases/antagonists & inhibitors/metabolism ; Humans ; Molecular Docking Simulation ; Drug Discovery ; Molecular Dynamics Simulation ; Blood-Brain Barrier/metabolism ; *Enzyme Inhibitors/pharmacology/chemistry ; },
abstract = {Alzheimer's disease (AD) remains a major neurodegenerative disorder with limited therapeutic medication. Despite intensive efforts, the clinical development of β-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitors has been hindered by off-target effects, poor brain penetration, and toxicity, which is often due to a lack of selectivity over BACE2. In this study, we conducted a comprehensive analysis of over 9,000 reported BACE1 inhibitors to identify key physicochemical properties and interaction fingerprints associated with effective binding. These criteria were used to filter a library of 1.4 million commercially available compounds, prioritizing candidates with better safety and blood-brain barrier (BBB) permeability properties. The top-ranked molecules were evaluated through molecular docking and molecular dynamics (MD) simulations, followed by selectivity assessments against BACE2 and additional off-targets. Among these, two compounds, MCULE-5138978734 and MCULE-2333131051, exhibited strong and stable binding to BACE1 with markedly reduced affinity for BACE2, suggesting improved selectivity. This integrative in silico framework demonstrates a rational strategy for the discovery of selective BACE1 inhibitors and highlights promising lead candidates for further experimental validation in the development of AD therapeutics.},
}

*Amyloid Precursor Protein Secretases/antagonists & inhibitors/metabolism
*Alzheimer Disease/drug therapy
*Aspartic Acid Endopeptidases/antagonists & inhibitors/metabolism
Humans
Molecular Docking Simulation
Drug Discovery
Molecular Dynamics Simulation
Blood-Brain Barrier/metabolism
*Enzyme Inhibitors/pharmacology/chemistry

@article {pmid41024623,
year = {2025},
author = {Tok, F and Baltaş, N and Abas, Bİ and Kozan, B and Kaya, S and Tatar-Yılmaz, G and Çevik, Ö},
title = {Synthesis, Biological Evaluation and Molecular Docking Studies of New 4-(Cyanomethyl)-N'-Substituted Benzohydrazide Derivatives as Anti-Alzheimer Agents.},
journal = {Drug development research},
volume = {86},
number = {7},
pages = {e70166},
doi = {10.1002/ddr.70166},
pmid = {41024623},
issn = {1098-2299},
support = {//The authors received no specific funding for this work./ ; },
mesh = {Molecular Docking Simulation ; *Cholinesterase Inhibitors/pharmacology/chemical synthesis/chemistry ; Humans ; *Alzheimer Disease/drug therapy ; Acetylcholinesterase/metabolism ; Cell Line, Tumor ; *Antioxidants/pharmacology/chemical synthesis/chemistry ; Structure-Activity Relationship ; Butyrylcholinesterase/metabolism ; *Hydrazines/pharmacology/chemical synthesis/chemistry ; Cell Survival/drug effects ; },
abstract = {Although the incidence of Alzheimer's disease increases with age, the number of effective drugs in the fight against this disease remains insufficient. In this regard, a new series of hydrazide-hydrazone derivative compounds (3a-3n) was synthesized and their structures were elucidated using spectral techniques. Then, all compounds were tested for their in vitro antioxidant and anticholinesterase activities. Compound 3i was found to have the highest antioxidant activity in the series with 63.750 ± 0.033 µM and 44.210 ± 0.058 µM SC50 values in the DPPH and ABTS methods, respectively. Compound 3i exhibited significantly higher inhibitory properties than the reference standard donepezil with IC50 values of 1.850 ± 0.013 µM and 3.680 ± 0.034 µM against AChE and BChE enzymes, respectively. The cytotoxicity and AChE inhibition potential of the compounds on the SH-SY5Y cell line were also evaluated. Compounds 3i and 3l were found to have the highest AChE inhibition (81.03 ± 2.05% and 83.84 ± 2.46%) in SH-SY5Y cells, respectively. Compound 3l also maintained cell viability at 100 µM concentration. The most active compounds in the series were investigated as competitive or noncompetitive inhibitors against AChE and BChE by enzyme kinetic studies. Moreover, molecular docking and MD simulation studies were used to describe the enzyme-ligand interactions and their stability.},
}

Molecular Docking Simulation
*Cholinesterase Inhibitors/pharmacology/chemical synthesis/chemistry
Humans
*Alzheimer Disease/drug therapy
Acetylcholinesterase/metabolism
Cell Line, Tumor
*Antioxidants/pharmacology/chemical synthesis/chemistry
Structure-Activity Relationship
Butyrylcholinesterase/metabolism
*Hydrazines/pharmacology/chemical synthesis/chemistry
Cell Survival/drug effects

@article {pmid41024619,
year = {2025},
author = {Guo, Q and Chen, C and Guo, L and Wang, Y and Shang, S},
title = {Association Between Cognitive Dysfunction, TYG Index, and Depression in Older Adults: Based on the NHANES Database, 2011-2014.},
journal = {Brain and behavior},
volume = {15},
number = {10},
pages = {e70824},
doi = {10.1002/brb3.70824},
pmid = {41024619},
issn = {2162-3279},
mesh = {Humans ; Aged ; Male ; Female ; *Cognitive Dysfunction/blood/epidemiology ; Cross-Sectional Studies ; Nutrition Surveys ; *Depression/blood/epidemiology ; Middle Aged ; *Blood Glucose/metabolism ; *Triglycerides/blood ; Aged, 80 and over ; United States/epidemiology ; Neuropsychological Tests ; Executive Function/physiology ; },
abstract = {BACKGROUND: The relationship between cognitive impairment, triglyceride-glucose (TyG) index, and depression in the elderly remains unclear. This study aims to explore the associations among cognitive impairment, TyG index, and the risk of depression in older adults, providing a basis for targeted prevention strategies.

METHODS: This cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2014. Depression was assessed using the Patient Health Questionnaire-9 (PHQ-9). Cognitive impairment was defined as the lowest quartile of three cognitive tests: the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) test for learning and memory, the Animal Fluency test for executive function, and the Digit Symbol Substitution Test (DSST) for attention and processing speed. The TyG index was calculated as ln[triglycerides (mg/dL) × fasting glucose (mg/dL)/2], and participants were categorized into quartiles based on their TyG index. Multivariable logistic regression models were employed to investigate the relationships between cognitive impairment, TyG index, and depression in the elderly.

RESULTS: A total of 2042 elderly participants (aged ≥ 60 years) were included in the study, among whom 312 (15.3%) were diagnosed with depression. Both cognitive impairment and higher TyG index were significantly associated with increased depressive symptoms among older adults in the United States. The risk of depression was 2.64 times higher (95% confidence interval [CI]: 1.33-5.23) in those with cognitive impairment compared to those with normal cognitive function. Participants in the highest TyG quartile had a multivariable-adjusted odds ratio (OR) of 1.61 (95% CI: 1.10-2.35) for depression compared to those in the lowest quartile. Similar results were observed across different genders, age groups, and baseline comorbidities.

CONCLUSION: Our findings suggest that higher TyG index and cognitive impairment (including deficits in learning and memory, executive function, and attention/processing speed) are associated with a greater likelihood of depressive symptoms in older adults.},
}

Humans
Aged
Male
Female
*Cognitive Dysfunction/blood/epidemiology
Cross-Sectional Studies
Nutrition Surveys
*Depression/blood/epidemiology
Middle Aged
*Blood Glucose/metabolism
*Triglycerides/blood
Aged, 80 and over
United States/epidemiology
Neuropsychological Tests
Executive Function/physiology

@article {pmid41024525,
year = {2025},
author = {Wright, MM and Shippee, TP and Skarphol, T and Flatt, J and Alberth, A and Moone, RP and Rosser, BRS},
title = {Recruiting Sexual and Gender Minority Older Adults With and Without Dementia in Long-Term Care: Overcoming Barriers and Lessons Learned.},
journal = {Journal of applied gerontology : the official journal of the Southern Gerontological Society},
volume = {},
number = {},
pages = {7334648251378797},
doi = {10.1177/07334648251378797},
pmid = {41024525},
issn = {1552-4523},
abstract = {Sexual and gender minority (SGM) older adults, including those in long-term care and living with cognitive impairment, are underrepresented in research. This study explored barriers and facilitators to recruiting SGM older adults using long-term services and supports (LTSS) into research. As part of a broader project on SGM policies in LTSS, we conducted qualitative interviews with 20 assisted living and nursing home administrators identified through a related survey. Thematic analysis revealed three key themes: difficulty identifying SGM residents, the need to address discrimination by other residents, and special considerations when working with SGM residents who have Alzheimer's disease or related dementias (AD/ADRD). These findings highlight the importance of developing strategies to identify SGM participants, mitigate discrimination, and ensure appropriate consent processes for those with cognitive impairment. The results offer guidance for researchers aiming to ethically and effectively include SGM older adults with AD/ADRD in LTSS settings.},
}