Alzheimer's & Dementia最新文献

{"title":"Return of research results across the Alzheimer's Disease Research Centers network","authors":"Annalise Rahman-Filipiak,&nbsp;Nathaniel A. Chin,&nbsp;Haley Kohl,&nbsp;Jonathan M. Reader,&nbsp;Claire M. Erickson,&nbsp;Bradford C. Dickerson,&nbsp;Neelum T. Aggarwal,&nbsp;Sterling C. Johnson,&nbsp;Elizabeth C. Mormino,&nbsp;Lindsay R. Clark","doi":"10.1002/alz.70418","DOIUrl":"https://doi.org/10.1002/alz.70418","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>The Consortium for Clarity in Alzheimer's Disease and Related Dementias Through Imaging (CLARiTI) Return of Results Core aims to develop tools and a framework for disclosing individual results at Alzheimer's Disease Research Centers (ADRCs). An understanding of current disclosure practices is necessary to generate this protocol.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>All 37 ADRCs received a survey between January and April 2024; 36 provided valid responses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Most ADRCs disclose diagnosis and cognitive results to participants with impairment, and disclosure of biomarker data (e.g., amyloid and tau positron emission tomography) has accelerated since 2019. Though less common, disclosure to unimpaired participants has increased since 2019. Motivators for disclosure include to thank participants, for recruitment/retention, and to help inform health-care decisions. Barriers include limited expertise and infrastructure, concerns about clinical actionability, and risks to participants.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>The ADRC network is invested in sharing research results. While some concerns remain, CLARiTI will critically evaluate a standardized approach to sharing these results.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Individual research results disclosure has increased significantly since 2019.</li>\u0000 \u0000 <li>Results are shared more frequently with cognitively unimpaired participants.</li>\u0000 \u0000 <li>Disclosure requires interdisciplinary teams including physicians and psychologists.</li>\u0000 \u0000 <li>Disclosure motivations include enhancing retention and supporting clinical care.</li>\u0000 \u0000 <li>Barriers include limited resources/expertise and potential participant risks.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 6","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70418","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339251","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":"The association between poor sleep health and Alzheimer's disease structural neuroimaging biomarkers","authors":"Emma Nolan,&nbsp;Yunyi Sun,&nbsp;Hui Shi,&nbsp;Derek Archer,&nbsp;Arden Perry,&nbsp;Kimberly Pechman,&nbsp;Niranjana Shashikumar,&nbsp;Bennett Landman,&nbsp;Marissa Gogniat,&nbsp;Dandan Liu,&nbsp;Panpan Zhang,&nbsp;Timothy J. Hohman,&nbsp;Angela L. Jefferson,&nbsp;Kelsie M. Full","doi":"10.1002/alz.70364","DOIUrl":"https://doi.org/10.1002/alz.70364","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Poor sleep may be a risk factor for neurodegeneration and Alzheimer's disease (AD). Few studies have examined objectively measured sleep with structural neuroimaging measures.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Vanderbilt Memory and Aging Project participants (<i>N</i> = 407; median age: 70 years) wore ActiGraph accelerometers for 10 days to estimate sleep regularity, timing, efficiency, duration, wake-after-sleep onset, and awakening length. Volume in brain regions of interest (ROIs) and AD signatures were quantified using 3T brain magnetic resonance imaging (MRI). Cross-sectional linear regression models were adjusted for sociodemographic and lifestyle factors, depression, cognitive status, and cardiovascular risk. ROI and McEvoy models were adjusted for total intracranial volume.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Greater sleep irregularity (<i>β</i>_Hippocampus= −0.12, <i>p</i> = 0.005; <i>β</i>_McEvoy= −0.07, <i>p</i> = 0.024) and longer awakening length (<i>β</i>_Hippocampus= −0.11, <i>p</i> = 0.009; <i>β</i>_Parietal= −0.08, <i>p</i> = 0.012) were associated with smaller volumes in ROIs related to AD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>More irregular and fragmented sleep was associated with smaller volume in ROIs vulnerable to AD, indicating a potential link between poor sleep and neurodegeneration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Associations between sleep and brain health are poorly understood.</li>\u0000 \u0000 <li>Gray matter atrophy by irregular sleep may imply Alzheimer's disease (AD) decline.</li>\u0000 \u0000 <li>Increased sleep irregularity is associated with smaller brain region volume.</li>\u0000 \u0000 <li>Sleep disruption, estimated by awakening length, is linked to AD-related brain volume.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 6","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70364","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339376","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":"Evaluation of cognitive, functional, and behavioral effects observed in EMERGE, a phase 3 trial of aducanumab in people with early Alzheimer's disease","authors":"Jeffrey Cummings,&nbsp;Sharon Cohen,&nbsp;Jennifer Murphy,&nbsp;Holly M. Brothers,&nbsp;Mina Nejati,&nbsp;Fiona Forrestal,&nbsp;Carl de Moor,&nbsp;John O'Gorman,&nbsp;John Harrison,&nbsp;Judith Jaeger,&nbsp;Catherine Jane Mummery,&nbsp;Anton P. Porsteinsson,&nbsp;Michele Potashman,&nbsp;Ying Tian,&nbsp;Lili Yang,&nbsp;Ping He,&nbsp;Samantha Budd Haeberlein","doi":"10.1002/alz.70224","DOIUrl":"https://doi.org/10.1002/alz.70224","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>In EMERGE (NCT02484547), participants receiving aducanumab had significantly less progression versus placebo on all prespecified clinical endpoints at week 78. Here, we explicate the clinical meaningfulness of these treatment effects by analyzing item-level data and the persistence of treatment benefit.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Participants with early Alzheimer's disease (AD) were stratified by apolipoprotein E (<i>APOE</i>) ε4 status and randomized (1:1:1) to receive low- or high-dose aducanumab, or placebo. Prespecified principal component analyses (PCAs) per the Statistical Analysis Plan were followed by post hoc examination of individual domains/items across all five clinical endpoints. Progression analysis assessed reduction in clinical decline.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>High-dose aducanumab demonstrated clinically meaningful slowing of progression across clinical endpoints measuring cognition, daily function, and behavioral symptoms. Delay of progression over 18 months was consistent across measures; treatment effects increased over time.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Across multiple analyses aducanumab slowed cognitive decline, prolonged functional independence, and attenuated behavioral symptoms in participants with early AD. These outcomes comprise the elements of a clinically meaningful response to treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Endpoints in EMERGE assessed different aspects of cognition, daily function, and behavioral symptoms.</li>\u0000 \u0000 <li>Treatment benefits were observed across subdomains on all five clinical endpoints.</li>\u0000 \u0000 <li>Aducanumab meaningfully slowed disease progression in participants with early AD.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 6","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70224","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339380","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":"Multimorbidity patterns and blood biomarkers of Alzheimer's disease in community-dwelling cognitively unimpaired older adults","authors":"Alessandra Marengoni,&nbsp;Giulia Grande,&nbsp;Martina Valletta,&nbsp;Caterina Gregorio,&nbsp;Amaia Calderón-Larrañaga,&nbsp;Matilda Dale,&nbsp;Claudia Fredolini,&nbsp;Bengt Winblad,&nbsp;Davide Liborio Vetrano","doi":"10.1002/alz.70411","DOIUrl":"https://doi.org/10.1002/alz.70411","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; INTRODUCTION&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Alzheimer's disease (AD) blood biomarkers hold clinical potential but their concentration may vary with somatic conditions.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; METHODS&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;We investigated the concentration of six AD blood biomarkers in relation to multimorbidity as disease count and four multimorbidity patterns in 2290 cognitively unimpaired older adults.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; RESULTS&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Levels of phosphorylated tau (p-tau)181, p-tau217, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) increased with increasing number of diseases. In multi-adjusted regressions, compared to individuals without multimorbidity, the anemia/sensory impairment pattern was associated with altered levels of all biomarkers except amyloid beta (Aβ)42/40, GFAP, and total tau (p-tau181: β = 0.18, 95% confidence interval [CI]: 0.08, 0.28; p-tau217: β = 0.11, 95% CI: 0.03, 0.18; NfL: β = 0.14, 95% CI: 0.06, 0.21) and the cardiometabolic/inflammatory pattern was associated with altered levels of all biomarkers except Aβ42/40 and GFAP (p-tau181: β = 0.24, 95% CI: 0.12, 0.36; p-tau217: β = 0.23, 95% CI: 0.14, 0.32; NfL: β = 0.32, 95% CI: 0.23, 0.40; total tau: β = 0.23, 95% CI: 0.07, 0.39). Results remained unchanged after excluding those who developed dementia in 15 years.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; DISCUSSION&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;More diseases and specific multimorbidity patterns altered the levels of several AD blood biomarkers, highlighting caution when using them in adults with complex health profiles.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Highlights&lt;/h3&gt;\u0000 \u0000 &lt;div&gt;\u0000 &lt;ul&gt;\u0000 \u0000 &lt;li&gt;In cognitively unimpaired older adults blood biomarkers of Alzheimer's disease varied depending on the number of chronic diseases and specific patterns of multimorbidity.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Phosphorylated tau (p-tau)181, p-tau217, neurofilament light chain (NfL), and glial fibrillary acidic protein levels increased along with increasing numbers of chronic diseases.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;P-tau181, p-tau217, and NfL levels were significantly higher in individuals in the anemia/sensory impairment and cardiometabolic/inflammatory multimorbidity patterns compared to those without multimorbidity.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Results remained unchanged after excluding participants who developed dementia during 15","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 6","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70411","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339381","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":"Making outcome measures matter: Why should “what matters to people living with dementia” matter to dementia researchers?","authors":"Siobhan T. Reilly,&nbsp;Andrew J. E. Harding","doi":"10.1002/alz.70359","DOIUrl":"https://doi.org/10.1002/alz.70359","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>This article provides an overview of evidence to support a call to action for dementia researchers to ensure that “what matters to people living with dementia” should be at the heart of any decision-making around the choices and design of outcome measures. There have been sufficient reviews observing how the outcome measures that have been used in previous research have not been those that have been valued by people living with dementia or their carers. If researchers continue to use existing measures that are not valued by people living with dementia, they will waste limited research resources by using measures that are not sufficiently sensitive to detect changes that might be attributed to interventions. It is time for researchers to collaborate internationally to ensure that resources are invested in designing and validating new approaches for measurement of psychosocial outcomes for those living with dementia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Outcome measures that have been used in previous research have not been those that have been valued by people living with dementia or their carers.</li>\u0000 \u0000 <li>Existing outcome measures have been shown not to be fit for purpose and tend to focus on symptom reduction or broad conceptualizations of quality of life.</li>\u0000 \u0000 <li>Dementia researchers will need to collaborate internationally to ensure that resources are invested in designing and validating new approaches for measurement of psychosocial outcomes for those living with dementia.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 6","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70359","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339382","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":"Integrating visual assessments and quantification methods for tau PET staging","authors":"Yuna Gu,&nbsp;Jihwan Yun,&nbsp;Alexis Moscoso,&nbsp;Michael Schöll,&nbsp;Daeun Shin,&nbsp;Eun Hye Lee,&nbsp;Heekyong Kang,&nbsp;Sohyun Yim,&nbsp;Hyunjin Jo,&nbsp;Jun Pyo Kim,&nbsp;Sung Hoon Kang,&nbsp;Hee Jin Kim,&nbsp;Duk L. Na,&nbsp;Henrik Zetterberg,&nbsp;Kaj Blennow,&nbsp;Fernando Gonzalez-Ortiz,&nbsp;Nicholas J Ashton,&nbsp;Hyemin Jang,&nbsp;Michael W. Weiner,&nbsp;Seung Hwan Moon,&nbsp;Hanna Cho,&nbsp;Jae Yong Choi,&nbsp;Kyung Rok Nam,&nbsp;Byung Hyun Byun,&nbsp;Su Yeon Park,&nbsp;Jeong Ho Ha,&nbsp;Soo Hyun Cho,&nbsp;Sang Won Seo,&nbsp;ADNI and K-ROAD study groups","doi":"10.1002/alz.70352","DOIUrl":"https://doi.org/10.1002/alz.70352","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>We compared visual assessments and quantification methods for tau positron emission tomography (PET) staging and evaluated plasma biomarkers and cognitive trajectories across amyloid and tau (AT) staging.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Tau PET scans from 289 Korea-Registries to Overcome Dementia and Accelerate Dementia Research (K-ROAD) participants were analyzed visually and quantitatively, with validation in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort (<i>n</i> = 870). Plasma biomarkers and cognitive measures were evaluated across AT stages.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>FreeSurfer without partial volume correction (PVC) achieved the highest area under the curve (AUC) for tau positivity (0.918), based on visual interpretation. The temporal meta-region excelled in moderate tau staging (AUC = 0.856), while the temporoparietal region performed best for advanced staging (AUC = 0.828). Quantification methods detected phosphorylated tau217 changes during intermediate transitions (e.g., A+/T− to A+/Tmod+) more effectively. Plasma biomarkers and cognitive measures progressively changed across AT stages, with consistent results in K-ROAD and ADNI cohorts.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>The complementary strengths of visual and quantification methods enhance tau PET staging by effectively capturing biomarker changes and cognitive trajectories.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Quantification partially outperformed visual assessments in detecting early tau burdens.</li>\u0000 \u0000 <li>Meta-temporal and temporoparietal regions of interest excelled in early and late tau staging.</li>\u0000 \u0000 <li>Quantification methods correlated with plasma phosphorylated tau217 and cognitive decline.</li>\u0000 \u0000 <li>Findings were validated across two independent cohorts (Korea-Registries to Overcome Dementia and Accelerate Dementia Research and Alzheimer's Disease Neuroimaging Initiative).</li>\u0000 \u0000 <li>The study highlights the complementary roles of visual and quantification methods.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 6","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70352","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339375","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":"NIAGADS: A data repository for Alzheimer's disease and related dementia genomics","authors":"Amanda Kuzma,&nbsp;Otto Valladares,&nbsp;Emily Greenfest-Allen,&nbsp;Heather Nicaretta,&nbsp;Maureen Kirsch,&nbsp;Youli Ren,&nbsp;Zivadin Katanic,&nbsp;Heather White,&nbsp;Andrew Wilk,&nbsp;Lauren Bass,&nbsp;Jascha Brettschneider,&nbsp;Luke Carter,&nbsp;Jeffrey Cifello,&nbsp;Wei-Hsuan Chuang,&nbsp;Kaylyn Clark,&nbsp;Prabhakaran Gangadharan,&nbsp;Jacob Haut,&nbsp;Pei-Chuan Ho,&nbsp;Wenhwai Horng,&nbsp;Taha Iqbal,&nbsp;Yumi Jin,&nbsp;Peter Keskinen,&nbsp;Alexis Lerro Rose,&nbsp;Michelle K. Moon,&nbsp;Joseph Manuel,&nbsp;Liming Qu,&nbsp;Flawless Robbins,&nbsp;Naveensri Saravanan,&nbsp;Jin Sha,&nbsp;Sam Tate,&nbsp;Yi Zhao,&nbsp;Alzheimer's Disease Sequencing Project,&nbsp;Laura Cantwell,&nbsp;Jake Gardner,&nbsp;Shin-Yi Chou,&nbsp;Jung-Ying Tzeng,&nbsp;William Bush,&nbsp;Adam Naj,&nbsp;Pavel Kuksa,&nbsp;Wan-Ping Lee,&nbsp;Yuk Yee Leung,&nbsp;Gerard Schellenberg,&nbsp;Li-San Wang","doi":"10.1002/alz.70255","DOIUrl":"https://doi.org/10.1002/alz.70255","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>The National Institute on Aging Genetics of Alzheimer's Disease Data Storage Site (NIAGADS) is the National Institute on Aging–designated national data repository for human genetics research on Alzheimer's disease and related dementias (ADRD). NIAGADS maintains a high-quality data collection for ADRD genetic/genomic research and supports genetics data production and analysis, including whole genome and exome sequence data from the Alzheimer's Disease Sequencing Project and other genotype/phenotype data, encompassing 211,000 samples. NIAGADS shares these data with hundreds of research groups around the world via the Data Sharing Service, a Federal Information Security Modernization Act moderate compliant cloud-based platform that fully supports the National Institutes of Health Genomic Data Sharing Policy. NIAGADS Open Access consists of multiple knowledge bases with genome-wide association summary statistics and rich annotations on the biological significance of genetic variants and genes across the human genome. As a one-stop access portal for Alzheimer's disease (AD) genetics, NIAGADS stands as a keystone in promoting collaborations to advance the understanding and treatment of AD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>The National Institute on Aging Genetics of Alzheimer's Disease Data Storage Site (NIAGADS) is a data repository for the storage of genetics and genomics data.</li>\u0000 \u0000 <li>NIAGADS houses data for Alzheimer's disease, related dementias, and healthy aging.</li>\u0000 \u0000 <li>NIAGADS offers open and qualified access data and knowledgebases to explore open access data.</li>\u0000 \u0000 <li>The Alzheimer's Disease Sequencing Project dataset is the largest Alzheimer's disease and related dementias joint called whole genome sequencing dataset (≈ 58,000 whole genomes).</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 6","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70255","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339239","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":"Differences in the soluble and insoluble proteome between primary tauopathies","authors":"Tomas Kavanagh,&nbsp;Kaleah Balcomb,&nbsp;Stephanie Trgovcevic,&nbsp;Laura Nementzik,&nbsp;Evgeny Kanshin,&nbsp;Glenda Halliday,&nbsp;Beatrix Ueberheide,&nbsp;Eleanor Drummond","doi":"10.1002/alz.70401","DOIUrl":"https://doi.org/10.1002/alz.70401","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Primary tauopathies, including corticobasal degeneration (CBD), Pick's disease (PiD), and progressive supranuclear palsy (PSP), have aggregated tau pathology in the brain. Many other proteins are likely altered in disease; however, these have not been well characterized.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We performed sarkosyl fractionation of <i>post mortem</i> human brain tissue to enrich soluble and insoluble proteins from CBD, PiD, and PSP cases (<i>n</i> = 5/group). We assessed differences in the soluble fraction, insoluble fraction, and protein solubility changes between diseases, followed by enrichment and correlation analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>CBD and PiD showed the greatest proteomic similarity in both the soluble and insoluble fractions, while PSP was the most divergent in comparison to other diseases. We observed critical changes in the solubility of lysosomal regulators, postsynaptic proteins, the extracellular matrix (ECM), and mitochondrial proteins.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>We have contrasted the solubility patterns of proteins across three tauopathies for the first time. Protein solubility differences reveal divergence in disease processes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Tau isoforms are differentially soluble in primary tauopathies</li>\u0000 \u0000 <li>PSP proteomics profile was the most divergent of the tauopathies examined</li>\u0000 \u0000 <li>SORT1 is highly insoluble in CBD and aggregates to different extents in tauopathies</li>\u0000 \u0000 <li>There are shifts in solubility for key signalling pathways; ROCK1 and JAK2</li>\u0000 \u0000 <li>Unique lysosomal proteins are more insoluble in distinct tauopathies</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 6","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70401","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339250","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":"Longitudinal study of body mass index in relation to Alzheimer's disease pathology and symptomatology in Down syndrome","authors":"Victoria L. Fleming,&nbsp;Brian C. Helsel,&nbsp;Lauren T. Ptomey,&nbsp;Benjamin L. Handen,&nbsp;Sharon J. Krinsky-McHale,&nbsp;Christy L. Hom,&nbsp;Matthew Zammit,&nbsp;Davneet Minhas,&nbsp;Weiquan Luo,&nbsp;Charles Laymon,&nbsp;Joseph H. Lee,&nbsp;Ira Lott,&nbsp;Annie Cohen,&nbsp;Beau M. Ances,&nbsp;Adam M. Brickman,&nbsp;Margaret Pulsifer,&nbsp;Isabel C. H. Clare,&nbsp;H. Diana Rosa,&nbsp;Florencia Lai,&nbsp;Jordan Harp,&nbsp;Fredrick Schmitt,&nbsp;Julie Price,&nbsp;Shahid H. Zaman,&nbsp;Elizabeth Head,&nbsp;Mark Mapstone,&nbsp;Bradley T. Christian,&nbsp;Ozioma Okonkwo,&nbsp;Sigan L. Hartley,&nbsp;Alzheimer's Biomarkers Consortium–Down Syndrome","doi":"10.1002/alz.70387","DOIUrl":"https://doi.org/10.1002/alz.70387","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Weight loss has been linked to early Alzheimer's disease (AD) pathology, possibly through metabolic dysregulation. We examined changes in body mass index (BMI) in relation to AD biomarkers (amyloid beta [Aβ] and tau) and cognitive decline in adults with Down syndrome (DS). We hypothesized that BMI decline would track with early AD pathology and cognitive decline.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Adults with DS (<i>N</i> = 467; <i>M_age</i>= 43.67 ± 10.06) completed one to four data cycles (≈16 months apart). Linear mixed models examined BMI change over time by age, positron emission tomography (PET) Aβ and tau, and changes in memory and dementia symptoms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>BMI declined with age-by-time (<i>β</i> = −0.014, <i>p</i> = 0.002) and baseline PET Aβ-by-time (<i>β</i> = −0.005, <i>p</i> = 0.002). On average, BMI decline began in the early 40s and was related to decline in memory and overall cognitive functioning.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Weight loss is associated with the presence of Aβ and cognitive decline in adults with DS. Longitudinal studies need to clarify directionality and biological mechanisms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Adults with Down syndrome (DS) are at an elevated risk for Down Syndrome assocaited Alzheimer's disease (DSAD).</li>\u0000 \u0000 <li>On average, adults with DS experience body mass index (BMI) decline beginning in their early 40s.</li>\u0000 \u0000 <li>Positron emission tomography amyloid beta deposition is associated with greater decline in BMI in adults with DS.</li>\u0000 \u0000 <li>Across time, AD-related memory declines are associated with BMI decline.</li>\u0000 \u0000 <li>BMI decline should be part of DSAD screening tools, as it is an important part of DSAD clinical disease expression.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 6","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70387","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339270","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 participants’ attitudes toward research in the CARE registry","authors":"Thomas J. Hoffmann,&nbsp;Janice Y. Tsoh,&nbsp;Oanh L. Meyer,&nbsp;Marian Tzuang,&nbsp;Bora Nam,&nbsp;Gabriel Fara-On,&nbsp;Daren Huang,&nbsp;Alka M Kanaya,&nbsp;Dolores Gallagher-Thompson,&nbsp;Quyen Vuong,&nbsp;Hye-Won Shin,&nbsp;Va’atausili Tofaeono,&nbsp;Joshua D. Grill,&nbsp;Van Ta Park","doi":"10.1002/alz.70372","DOIUrl":"https://doi.org/10.1002/alz.70372","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Elucidating barriers and facilitators to research participation is especially important in Asian American, Native Hawaiian, and Pacific Islander (AANHPI) populations, who are significantly underrepresented in Alzheimer's disease and related dementias (ADRD) research.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We analyzed multilingual data from the 7-item Research Attitude Questionnaire (RAQ) among diverse AANHPI participants across a broad age range in the Collaborative Approach for AANHPI Research and Education (CARE) registry.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Upon enrollment, 10,063 CARE participants were invited to complete the RAQ; 72.3% (7281) did so. The RAQ survey showed that 75.0% had favorable attitudes toward research. In a stepwise model, characteristics associated with a more favorable attitude toward research included identifying as Vietnamese, older age, providing multiple contact methods, living in the Western U.S. region, and having better general health.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Attitudes toward research differ based on specific characteristics. Certain subpopulations may require more tailored and/or resource-intensive engagement to increase their research participation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Understanding research participation barriers is crucial in those underrepresented.</li>\u0000 \u0000 <li>Seventy-five percent of Collaborative Approach for Asian Americans, Native Hawaiians and Pacific Islanders Research and Education (CARE) registry members had favorable research attitudes.</li>\u0000 \u0000 <li>The study identified characteristics associated with research attitudes.</li>\u0000 \u0000 <li>Subpopulations may require more tailored and/or resource-intensive engagement.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 6","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70372","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339374","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}