Alzheimer's & Dementia最新文献

{"title":"Metabolic dysregulation in Alzheimer's disease: A brain metabolomics approach","authors":"Anke Hüls,&nbsp;Youran Tan,&nbsp;Emma Casey,&nbsp;Zhenjiang Li,&nbsp;Marla Gearing,&nbsp;Allan I. Levey,&nbsp;James J. Lah,&nbsp;Aliza P. Wingo,&nbsp;Dean P. Jones,&nbsp;Douglas I. Walker,&nbsp;Thomas S. Wingo,&nbsp;Donghai Liang","doi":"10.1002/alz.70528","DOIUrl":"10.1002/alz.70528","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>This study aimed to identify specific biological pathways and molecules involved in Alzheimer's disease (AD) neuropathology.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We conducted cutting-edge high-resolution metabolomics profiling of 162 human frontal cortex samples from the Emory Alzheimer's Disease Research Center (ADRC) brain bank with comprehensive neuropathological evaluations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>We identified 155 unique metabolic features and 36 pathways associated with three well-established AD neuropathology markers. Of these, 18 novel metabolites were confirmed with level 1 evidence, implicating their involvement in amino acid metabolism, lipid metabolism, carbohydrate metabolism, nucleotide metabolism, and metabolism of cofactors and vitamins in AD neuropathology. Genetic variability influenced these associations, with non-carriers of the apolipoprotein E (<i>APOE</i>) ε4 allele showing stronger perturbations in metabolites including glucose and adenosine 5′-diphosphoribose.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>This study demonstrates the potential of high-resolution metabolomic profiling in brain tissues to elucidate molecular mechanisms underlying AD pathology. Our findings provide critical insights into metabolic dysregulation in AD and its interplay with genetic factors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>This is one of the largest untargeted metabolomics studies of human brain tissue.</li>\u0000 \u0000 <li>155 metabolic features, and 36 metabolic pathways were linked to Alzheimer's disease (AD) neuropathology.</li>\u0000 \u0000 <li>Of these, 18 unique metabolites were confirmed with level 1 evidence.</li>\u0000 \u0000 <li>Glucose and adenosine 5′-diphosphoribose identified as key metabolic alterations in AD.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70528","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investment in Alzheimer's disease research for the next generation of adults with Down syndrome will yield health benefits for future generations","authors":"Margaret M. Weden,&nbsp;Lori Frank,&nbsp;Andrew W. Dick,&nbsp;Zetianyu Wang,&nbsp;Susan Peschin,&nbsp;Diane E. Bovenkamp,&nbsp;Sharyn L. Rossi,&nbsp;Dana Sciullo,&nbsp;Hampus Hillerstrom,&nbsp;Richard A. Fisher","doi":"10.1002/alz.70348","DOIUrl":"10.1002/alz.70348","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Recent innovations in Alzheimer's disease (AD) treatment highlight critical gaps in knowledge about how to support healthy aging of adults with Down syndrome (DS). RAND researchers updated demographic and epidemiological evidence about the DS population to assess the impact of increased investment in treatment innovations for DS-associated Alzheimer's disease (DS-AD). They estimated life expectancy at birth in 2020 to be 55 years, with ≈ 5 years of DS-AD. They found that the results of investment were dramatic. Between 2020 and 2070, adult years of life are expected to increase by 5 years without any increase in unhealthy years of life with DS-AD. Caregiving hours for individuals with DS-AD are expected to be reduced by 40%, which will generate large annual savings. The new evidence underscores the magnitude of the impact that investment in DS-AD treatments could have for individuals with DS, their families, and caregivers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Evidence is sparse about treatment for Down syndrome (DS)-associated Alzheimer's disease (DS-AD) and healthy aging of DS adults.</li>\u0000 \u0000 <li>This population simulation model estimates DS-AD caregiving costs at ≈ $1 billion per year.</li>\u0000 \u0000 <li>DS-AD innovations could increase life expectancy by 5 years and reduce caregiving by 40% by 2070.</li>\u0000 \u0000 <li>This better forecasting can improve policy and service planning.</li>\u0000 \u0000 <li>DS-AD research investment could yield dramatic gains for individuals and families.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70348","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145021936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Measuring alignment between the ADRC UDS data elements, FDA, and EHR data standards","authors":"Zhan Wang,&nbsp;Kayla Torres,&nbsp;Helen Foster,&nbsp;Gary Walker,&nbsp;Maryam Y. Garza,&nbsp;Amy Palmer,&nbsp;Elizabeth C. LeRoy,&nbsp;Rhonda Facile,&nbsp;Melissa Kirwin,&nbsp;Meredith N. Zozus","doi":"10.1002/alz.70628","DOIUrl":"10.1002/alz.70628","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>We compared and measured alignment between the Health Level Seven (HL7) Fast Healthcare Interoperability Resources (FHIR) standard used by electronic health records (EHRs), the Clinical Data Interchange Standards Consortium (CDISC) standards used by industry, and the Uniform Data Set (UDS) used by the Alzheimer's Disease Research Centers (ADRCs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>The ADRC UDS, consisting of 5959 data elements across eleven packets, was mapped to FHIR and CDISC standards by two independent mappers, with discrepancies adjudicated by experts.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Forty-five percent of the 5959 UDS data elements mapped to the FHIR standard, indicating possible electronic obtainment from EHRs. Ninety-four percent mapped to the CDISC standards, demonstrating high compatibility with industry standards.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>The study highlights the feasibility of harmonizing ADRC data with industry and clinical standards. CDISC demonstrated superior alignment with ADRC UDS data, whereas FHIR showed potential for improvement through resource maturation and enhanced standardization.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Forty-five percent of Alzheimer's Disease Research Center Uniform Data Set (ADRC UDS) data elements could be mapped to Fast Healthcare Interoperability Resources (FHIR), indicating potential electronic health records (EHRs) extraction.</li>\u0000 \u0000 <li>Ninety-four percent of ADRC UDS data elements could be mapped to Clinical Data Interchange Standards Consortium (CDISC) Study Data Tabulation Model (SDTM), showing high industry compatibility.</li>\u0000 \u0000 <li>Identified areas for improving data standards harmonization in Alzheimer's disease and related dementias (ADRD) research.</li>\u0000 \u0000 <li>Systematic mapping method aligns ADRC UDS with Health Level Seven (HL7) FHIR and CDISC SDTM standards.</li>\u0000 \u0000 <li>Results support feasibility of data sharing across ADRC research, EHRs, and industry.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70628","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145021966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retinal biomarkers in cognitive impairment and dementia: Structural, functional, and molecular insights","authors":"Yan Min,&nbsp;Hongyu Zhou,&nbsp;Zixiao Li,&nbsp;Yongjun Wang","doi":"10.1002/alz.70672","DOIUrl":"10.1002/alz.70672","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Cognitive impairment and dementia, including Alzheimer's disease (AD), pose a global health crisis, necessitating non-invasive biomarkers for early detection. This review highlights the retina, an accessible extension of the central nervous system (CNS), as a window to cerebral pathology through structural, functional, and molecular alterations. By synthesizing interdisciplinary evidence, we identify retinal biomarkers as promising tools for early diagnosis and risk stratification. Nevertheless, translating biomarkers into clinical practice faces significant translational hurdles, including methodological heterogeneity, confounding variables, lack of standardized protocols, and insufficient longitudinal validation in diverse populations. Overcoming these challenges through rigorous standardization and robust validation studies is essential to establish the clinical utility of retinal biomarkers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Stage-specific diagnostic potential: Retinal biomarkers (e.g., OCT/OCTA changes, eye movements, molecular deposits) show alterations correlating with cognitive impairment stages (preclinical AD to dementia), assisting stage differentiation.</li>\u0000 \u0000 <li>Reflecting cerebral pathology: Multimodal retinal alterations (structural, functional, molecular) correlate with key brain pathologies (amyloid/tau burden, atrophy, small vessel disease), indicating shared pathways.</li>\u0000 \u0000 <li>Translation gaps and future: Clinical adoption faces barriers (method heterogeneity, confounders, limited validation). Future requires rigorous screening of candidate retinal biomarkers, extensive multicenter validation, and artificial intelligence (AI)-facilitated clinical translation.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70672","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145022077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Familial Alzheimer's disease mutation identifies novel role of SORLA in release of neurotrophic exosomes","authors":"Kristian Juul-Madsen,&nbsp;Ina-Maria Rudolph,&nbsp;Jemila P. Gomes,&nbsp;Katrina Meyer,&nbsp;Peter L. Ovesen,&nbsp;Malgorzata Gorniak-Walas,&nbsp;Marianna Kokoli,&nbsp;Narasimha S. Telugu,&nbsp;Malthe von Tangen Sivertsen,&nbsp;Fabia Febbraro,&nbsp;Duncan S. Sutherland,&nbsp;Johan Palmfeldt,&nbsp;Sebastian Diecke,&nbsp;Olav M. Andersen,&nbsp;Matthias Selbach,&nbsp;Thomas E. Willnow","doi":"10.1002/alz.70591","DOIUrl":"10.1002/alz.70591","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Mutations in <i>SORL1</i>, encoding the sorting receptor Sortilin-related receptor with A-type repeats (SORLA), are found in individuals with Alzheimer's disease (AD). We studied SORLA^N1358S, carrying a mutation in its ligand binding domain, to learn more about receptor functions relevant for human brain health.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We investigated consequences of SORLA^N1358S expression in induced pluripotent stem cell (iPSC)-derived human neurons and microglia, using unbiased proteome screens and functional cell assays.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>We identified alterations in the SORLA^N1358S interactome linked to biogenesis of exosomes. Consequently, the mutant receptor failed to promote release and neurotrophic qualities of exosomes, a defect attributed to altered exosomal content of microRNAs controlling neuronal maturation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>We identified a role for SORLA in controlling quantity and neurotrophic quality of exosomes secreted by cells, suggesting impaired cellular cross talk through exosomes as a pathological trait contributing to AD pathology in carriers of <i>SORL1</i> variants.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Familial Alzheimer's disease mutation in <i>SORL1</i> changes interactome of mutant Sortilin-related receptor with A-type repeats (SORLA).</li>\u0000 \u0000 <li>Mutant SORLA impairs release of exosomes from neurons and microglia.</li>\u0000 \u0000 <li>Mutant exosomes lack neurotrophic qualities.</li>\u0000 \u0000 <li>Defect linked to alterations in microRNA content.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70591","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145022074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Age-related amyloid beta dynamics modeled with the generalized additive model for location, scale, and shape (GAMLSS) across diverse populations: Cross-sectional trajectories and longitudinal validation","authors":"Sungjoo Lee,&nbsp;Min Young Chun,&nbsp;Hyemin Jang,&nbsp;Michael Weiner,&nbsp;Suzanne E. Schindler,&nbsp;Daeun Shin,&nbsp;Heekyung Kang,&nbsp;Sohyun Yim,&nbsp;Eun Hye Lee,&nbsp;Kyunga Kim,&nbsp;Hee Jin Kim,&nbsp;Duk L. Na,&nbsp;Jun Pyo Kim,&nbsp;Sang Won Seo,&nbsp;the ADNI, A4, and K-ROAD studies","doi":"10.1002/alz.70675","DOIUrl":"10.1002/alz.70675","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>We developed and validated age-related amyloid beta (Aβ) positron emission tomography (PET) trajectories using a statistical model in cognitively unimpaired (CU) individuals.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We analyzed 849 CU Korean and 521 CU non-Hispanic White (NHW) participants after propensity score matching. Aβ PET trajectories were modeled using the generalized additive model for location, scale, and shape (GAMLSS) based on baseline data and validated with longitudinal data. Subgroup analyses examined apolipoprotein E (<i>APOE</i>) ε4 and sex effects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Age-related centile curves of Aβ PET Centiloid values showed stable distributions in the lower percentiles, increasing with age in the upper percentiles. NHWs exhibited steeper Aβ accumulation trajectories, particularly among <i>APOE</i> ε4 carriers. Calibration with longitudinal data confirmed the reliability of this cross-sectional method.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>We developed a statistical model of age-related Aβ PET trajectories using baseline data, validated with longitudinal data. NHWs exhibited steeper trajectories than Koreans, suggesting population-specific differences in Aβ accumulation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>A generalized additive model for location, scale, and shape model was applied to examine age-related amyloid beta (Aβ) trajectories with baseline data.</li>\u0000 \u0000 <li>Trajectories were validated using longitudinal data, confirming model reliability.</li>\u0000 \u0000 <li>Non-Hispanic Whites exhibited steeper trajectories than Koreans, especially in apolipoprotein E ε4 carriers.</li>\u0000 \u0000 <li>Our approach enables scalable modeling of Aβ dynamics for Alzheimer's disease prevention strategies.</li>\u0000 \u0000 <li>Findings highlight the importance of multi-ethnic research in Aβ accumulation.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70675","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145022076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Understanding brain donation decisions: Predictors of indecision and change over time from the Cleveland Alzheimer's Disease Research Center","authors":"Lyndsi Powell,&nbsp;David Silva,&nbsp;Alexsandra Kovacevich,&nbsp;Jagan Pillai,&nbsp;Audrey Lynn,&nbsp;Sunah Song,&nbsp;Brian S. Appleby","doi":"10.1002/alz.70698","DOIUrl":"10.1002/alz.70698","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Little is known about factors influencing indecision or changes in brain donation program (BDP) enrollment status among Alzheimer's disease and related dementias research participants. This study examined demographic features associated with these decisions in participants from the Cleveland Alzheimer's Disease Research Center (CADRC).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Demographics and BDP status were extracted from the CADRC database and analyzed based on initial and current BDP enrollment status.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>At baseline, BDP enrollees were more likely to be older, cognitively impaired, White, partnered, have more years of education, and have a relative or partner serving as a study partner. Participants who changed BDP status over time were more often cognitively unimpaired and had more CADRC visits. Fewer years of education predicted changing from “undecided” to “yes.” Enrollment rates varied significantly between study staff.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Several demographic features are associated with uncertainty or change in BDP enrollment. These factors should be further examined to optimize ADRC participants’ experience.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Twenty-one percent of participants changed their brain donation program (BDP) enrollment status during the study.</li>\u0000 \u0000 <li>BDP enrollment changers were more often cognitively normal and had more study visits.</li>\u0000 \u0000 <li>Fewer years of education predicted switching BDP status from undecided to yes.</li>\u0000 \u0000 <li>BDP enrollment and change rates varied between interactions with site staff members.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70698","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145022078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Boston University Alzheimer's Disease Research Center Clinical Core: Infrastructure to facilitate research on post-traumatic Alzheimer's disease and related dementias","authors":"Michael L. Alosco,&nbsp;Madeline Morrison,&nbsp;Rhoda Au,&nbsp;Eric G. Steinberg,&nbsp;Jane Mwicigi,&nbsp;Monica Ly,&nbsp;Caroline Altaras,&nbsp;Steve Lenio,&nbsp;Myriam Abdennadher,&nbsp;Maureen K. O'Connor,&nbsp;Yorghos Tripodis,&nbsp;Joseph Palmisano,&nbsp;Diane Dixon,&nbsp;Brett Martin,&nbsp;Greta Schneider,&nbsp;Jenna R. Groh,&nbsp;Andrew Ellison,&nbsp;Dean Sheppard,&nbsp;Chad W. Farris,&nbsp;Christopher Nowinski,&nbsp;Robert C. Cantu,&nbsp;Katherine W. Turk,&nbsp;Lindsay Farrer,&nbsp;Gyungah Jun,&nbsp;Lee E. Goldstein,&nbsp;Wei Qiao Qiu,&nbsp;Thor D. Stein,&nbsp;Andrew E. Budson,&nbsp;Ann C. McKee,&nbsp;Jesse Mez","doi":"10.1002/alz.70654","DOIUrl":"10.1002/alz.70654","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>We describe the rationale, methodology, and design of the Boston University Alzheimer's Disease Research Center (BU ADRC) Clinical Core (CC). The CC characterizes a longitudinal cohort of participants with/without brain trauma to characterize the clinical presentation, biomarker profiles, and risk factors of post-traumatic Alzheimer's disease (AD) and AD-related dementias (ADRD), including chronic traumatic encephalopathy (CTE). Participants complete assessments of traumatic brain injury (TBI) and repetitive head impacts (RHIs); annual Uniform Data Set (UDS) and supplementary evaluations; digital phenotyping; annual blood draw; magnetic resonance imaging (MRI) and lumbar puncture every 3 years; electroencephalogram (EEG); and amyloid and/or tau positron emission tomography (PET) on a subset. As of 3/2025, the CC consists of 467 participants (mean age: 65.6, 50.1% female), including 163 RHI and 302 TBI who completed a UDS 3.0 baseline visit. Common sources of RHI included football (<i>n</i> = 95), soccer (<i>n</i> = 26), ice hockey (<i>n</i> = 17), and military service (<i>n</i> = 46). Most TBIs were mild (97.7%). Eighty-nine percent agreed to brain donation. The BU ADRC CC will facilitate research, education, and training on post-traumatic AD/ADRD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>The Boston University Alzheimer's Disease Research Center (ADRC) Clinical Core facilitates unique research, education, and training on Alzheimer's disease and Alzheimer's disease-related dementias (AD/ADRD) with a focus on post-traumatic AD/ADRD, including chronic traumatic encephalopathy (CTE).</li>\u0000 \u0000 <li>We summarize the rationale, mission, study design, and recent updates for the Clinical Core.</li>\u0000 \u0000 <li>As of March 2025, the Clinical Core includes a longitudinal cohort of 467 participants enriched for repetitive head impacts (∼1/3) and traumatic brain injury (∼1/3) exposure who span the cognitive continuum, with most having available fluid and neuroimaging biomarker data and agreeing to brain donation (89%).</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70654","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145012884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiometabolic disorders and mild cognitive impairment in White and Black Americans","authors":"Voyko Kavcic,&nbsp;Mohammad Turaani,&nbsp;Subhamoy Pal,&nbsp;Jonathan M. Reader,&nbsp;Bruno Giordani","doi":"10.1002/alz.70642","DOIUrl":"10.1002/alz.70642","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Mild cognitive impairment (MCI) represents a transitional stage between normal aging and dementia. We investigate associations among cardiovascular and metabolic disorders (hypertension, diabetes mellitus, and hyperlipidemia) and diagnosis (normal; amnestic [aMCI]; and non-amnestic [naMCI]).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Multinomial logistic regressions of participant data (<i>N</i> = 8737; age = 70.9 ± 7.5 years) from the National Alzheimer's Coordinating Center Uniform Dataset Version 3 protocol cohort were used.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Controlling for demographic/health variables, individuals with aMCI, though not naMCI, showed a higher likelihood of hypertension, diabetes, and hyperlipidemia compared to cognitively normal counterparts, though no differences between aMCI/naMCI. Black Americans, regardless of cognitive status, were more likely to fall into hypertension and diabetes groups compared to White Americans.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>These findings underscore the critical role of diagnosis and race in MCI diagnosis and care, emphasizing the need for tailored interventions to address inequities and reduce the risk of progression to dementia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>The study leverages a large, racially diverse cohort from the NACC database. </li>\u0000 \u0000 <li>Black Americans with non-amnestic mild cognitive impairment(naMCI) show highest comorbidity burden.</li>\u0000 \u0000 <li>No significant differences in comorbidity burden between amnestic MCI (aMCI) and naMCI subtypes. </li>\u0000 \u0000 <li>Education is protective, but less so for Black American individuals.</li>\u0000 \u0000 <li>Older age, male sex, body mass index (BMI), and low education associate with increased risk for comorbidities.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70642","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145022252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma lipidome dysregulation in frontotemporal dementia reveals shared, genotype-specific, and severity-linked alterations","authors":"Yohannes A. Ambaw,&nbsp;Peter A. Ljubenkov,&nbsp;Shubham Singh,&nbsp;Abdi Hamed,&nbsp;Sebastian Boland,&nbsp;Adam L. Boxer,&nbsp;Tobias C. Walther,&nbsp;Robert V. Farese Jr.","doi":"10.1002/alz.70631","DOIUrl":"10.1002/alz.70631","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Biomarkers are essential for monitoring the progression of frontotemporal dementia (FTD). Although dysregulated brain lipid metabolism, particularly sphingolipids enriched in the nervous system, is a key feature of neurodegeneration, plasma lipids remain underexplored as biomarkers compared to imaging and serum proteins.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We examined plasma lipidomes using liquid chromatography–tandem mass spectrometry (LC-MS/MS) from individuals carrying pathogenic variants linked to autosomal dominant FTD (<i>GRN</i>, <i>C9orf72</i>, <i>MAPT</i>) and non-carriers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>FTD subjects exhibited increased plasma levels of gangliosides (GM3(d18:1_16:0), GM3(d18:1_24:1)), ceramide Cer(d18:1_23:0), and select polyunsaturated triacylglycerols. In contrast, phosphatidylethanolamine (PE(18:0_24:0) and sphingomyelin (SM(38:0) were reduced. Subtype-specific changes included elevated glucosylsphingosine (GlcSph(d18:1) in <i>GRN</i> carriers, reduced SM(34:1) in <i>C9orf72</i>, and decreased TG(16:0_18:1_20:3) in <i>MAPT</i> carriers. GM3(d18:1_16:0) was consistently elevated across all subtypes. Furthermore, the levels of these lipids correlated with disease severity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Our findings suggest that specific plasma lipid changes, notably several sphingolipids, may be useful biomarkers for FTD disease or progression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Plasma lipidomics reveals both shared and mutation-specific lipid alterations in frontotemporal dementia (FTD).</li>\u0000 \u0000 <li>Glucosylsphingosine is specifically elevated in FTD caused by <i>GRN</i> mutations and correlates with disease severity.</li>\u0000 \u0000 <li>The ganglioside GM3(d18:1_16:0) is consistently elevated across <i>GRN, MAPT, and C9orf72</i> variants and correlates with disease severity.</li>\u0000 \u0000 <li>Plasma sphingolipids emerge as promising biomarkers for FTD diagnosis, subtype differentiation, and disease monitoring.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70631","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145012334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}