Alzheimer's & Dementia最新文献

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Combining plasma p-tau231 and glial fibrillary acidic protein produces higher discriminative accuracy for amyloid positivity than other blood-based biomarker combinations 结合血浆p-tau231和胶质纤维酸性蛋白对淀粉样蛋白阳性的鉴别准确性高于其他基于血液的生物标志物组合
IF 11.1 1区 医学
Alzheimer's & Dementia Pub Date : 2025-10-09 DOI: 10.1002/alz.70796
Corey J. Bolton, Omair A. Khan, Dandan Liu, Kimberly R. Pechman, Katherine A. Gifford, Timothy J. Hohman, Kaj Blennow, Henrik Zetterberg, Angela L. Jefferson
{"title":"Combining plasma p-tau231 and glial fibrillary acidic protein produces higher discriminative accuracy for amyloid positivity than other blood-based biomarker combinations","authors":"Corey J. Bolton,&nbsp;Omair A. Khan,&nbsp;Dandan Liu,&nbsp;Kimberly R. Pechman,&nbsp;Katherine A. Gifford,&nbsp;Timothy J. Hohman,&nbsp;Kaj Blennow,&nbsp;Henrik Zetterberg,&nbsp;Angela L. Jefferson","doi":"10.1002/alz.70796","DOIUrl":"10.1002/alz.70796","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Plasma phosphorylated tau<sub>231</sub> (p-tau<sub>231</sub>) has shown great promise for early identification of amyloid pathology. We tested various plasma biomarker combinations with p-tau231 in relation to cerebrospinal fluid (CSF) amyloid positivity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>One hundred and fifty-five dementia-free older adults were included. Plasma p-tau231, glial fibrillary acidic protein (GFAP), β-amyloid42/40, and neurofilament light chain (NfL) were related to amyloid positivity via logistic regression. Subsequent models assessing various combinations of biomarkers were compared to a base model containing only p-tau<sub>231</sub>.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>In single predictor models, p-tau231 (AUC = 0.87, <i>p</i> = 0.005) and GFAP (AUC = 0.87, <i>p</i> = 0.01) were associated with amyloid positivity, and p-tau231 remained significant in all multi-predictor models (<i>p</i>-values &lt; 0.02). In comparison to the base model with p-tau231 only, models adding GFAP improved the prediction of amyloid positivity (<i>p</i> &lt; 0.03).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Plasma p-tau231 and GFAP were associated with amyloid positivity. Models including both p-tau231 and GFAP performed best, while including β-amyloid42/40 and NfL did not produce a better fitting model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Plasma p-tau231 and glial fibrillary acidic protein (GFAP) are accurate predictors of amyloid positivity.</li>\u0000 \u0000 <li>Combining plasma p-tau231 and GFAP improves accuracy.</li>\u0000 \u0000 <li>Adding other biomarkers beyond p-tau231 and GFAP does not improve models.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 10","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70796","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145247358","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}
引用次数: 0
Alzheimer's disease–associated PLCG2 variants alter microglial state and function in human induced pluripotent stem cell–derived microglia-like cells 阿尔茨海默病相关PLCG2变异改变人诱导多能干细胞衍生的小胶质样细胞的小胶质状态和功能。
IF 11.1 1区 医学
Alzheimer's & Dementia Pub Date : 2025-10-09 DOI: 10.1002/alz.70772
Logan M. Bedford, Kaylee D. Tutrow, Karly Hooper, Evan J. Messenger, Melody Hernandez, Bruce T. Lamb, Jason S. Meyer, Timothy I. Richardson, Stephanie J. Bissel
{"title":"Alzheimer's disease–associated PLCG2 variants alter microglial state and function in human induced pluripotent stem cell–derived microglia-like cells","authors":"Logan M. Bedford,&nbsp;Kaylee D. Tutrow,&nbsp;Karly Hooper,&nbsp;Evan J. Messenger,&nbsp;Melody Hernandez,&nbsp;Bruce T. Lamb,&nbsp;Jason S. Meyer,&nbsp;Timothy I. Richardson,&nbsp;Stephanie J. Bissel","doi":"10.1002/alz.70772","DOIUrl":"10.1002/alz.70772","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;Variants of phospholipase C gamma 2 (PLCG2), a key microglial immune signaling protein, are genetically linked to Alzheimer's disease (AD) risk. Understanding how PLCG2 variants alter microglial function is critical for identifying mechanisms that drive neurodegeneration or resiliency in AD.&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;Induced pluripotent stem cell (iPSC) –derived microglia carrying the protective PLCG2&lt;sup&gt;P522R&lt;/sup&gt; or risk-conferring PLCG2&lt;sup&gt;M28L&lt;/sup&gt; variants, or loss of PLCG2, were generated to ascertain the impact on microglial transcriptome and function.&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;Protective PLCG2&lt;sup&gt;P522R&lt;/sup&gt; microglia showed significant transcriptomic similarity to isogenic controls. In contrast, risk-conferring PLCG2&lt;sup&gt;M28L&lt;/sup&gt; microglia shared similarities with PLCG2&lt;sup&gt;KO&lt;/sup&gt; microglia, with functionally reduced TREM2 expression, blunted inflammatory responses, and increased proliferation and cell death. Uniquely, PLCG2&lt;sup&gt;P522R&lt;/sup&gt; microglia showed elevated cytokine secretion after lipopolysaccharide (LPS) stimulation and were protected from apoptosis.&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;These findings demonstrate that PLCG2 variants drive distinct microglia transcriptomes that influence microglial functional responses that could contribute to AD risk and protection. Targeting PLCG2-mediated signaling may represent a powerful therapeutic strategy to modulate neuroinflammation.&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;The impact of Alzheimer's disease protective- and risk-associated variants of phospholipase C gamma 2 (PLCG2) on the transcriptome and function of induced pluripotent stem cell (iPSC) –derived microglia was investigated.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;PLCG2 risk variant microglia exhibited a basal transcriptional profile similar to PLCG2-deficient microglia but significantly different from isotype control and the transcriptionally similar PLCG2 protective variant microglia.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;PLCG2 risk variant and PLCG2-deficient microglia show decreased levels of triggering receptor expressed on myeloid cells 2 (TREM2).&lt;/li&gt;\u0000 \u0000 &lt;li&gt;The differential transcriptional pathways of protective and risk-associated PLCG2 variant microglia functionally","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 10","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70772","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145247122","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}
引用次数: 0
Intestinal inflammation induces glymphatic remodeling, priming early neurodegenerative signals in male mice 肠道炎症诱导淋巴重塑,引发雄性小鼠早期神经退行性信号
IF 11.1 1区 医学
Alzheimer's & Dementia Pub Date : 2025-10-09 DOI: 10.1002/alz.70640
Clara Ciampi, Francesca Fagiani, Valentina Murtaj, Federica Comella, Veronica Torre, Marta Filibian, Annapaola Andolfo, Clarissa Braccia, Nicola Opallo, Maria Grazia Bottone, Edoardo Pedrini, Elena Lucarini, Maria Bove, Stefano Govoni, Carla Ghelardini, Rosaria Meli, Luigia Trabace, Anna Pittaluga, Giuseppina Mattace Raso, Lorenzo Di Cesare Mannelli, Cristina Lanni
{"title":"Intestinal inflammation induces glymphatic remodeling, priming early neurodegenerative signals in male mice","authors":"Clara Ciampi,&nbsp;Francesca Fagiani,&nbsp;Valentina Murtaj,&nbsp;Federica Comella,&nbsp;Veronica Torre,&nbsp;Marta Filibian,&nbsp;Annapaola Andolfo,&nbsp;Clarissa Braccia,&nbsp;Nicola Opallo,&nbsp;Maria Grazia Bottone,&nbsp;Edoardo Pedrini,&nbsp;Elena Lucarini,&nbsp;Maria Bove,&nbsp;Stefano Govoni,&nbsp;Carla Ghelardini,&nbsp;Rosaria Meli,&nbsp;Luigia Trabace,&nbsp;Anna Pittaluga,&nbsp;Giuseppina Mattace Raso,&nbsp;Lorenzo Di Cesare Mannelli,&nbsp;Cristina Lanni","doi":"10.1002/alz.70640","DOIUrl":"10.1002/alz.70640","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Inflammatory bowel disease triggers extraintestinal manifestations, including in the central nervous system (CNS). However, the direct impact of peripheral inflammation on the CNS is largely unknown.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Using a mouse model of colitis with pain and anxiety-like behavior, we investigated the intricate pathogenic link between colonic inflammation, disruptions in circadian rhythmicity and impaired glymphatic circulation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>By in vivo magnetic resonance imaging, we observed a derangement of brain fluid dynamics, with a significant enlargement of the cerebral lateral ventricles and waste deposition within the brain parenchyma. Proteomics revealed changes in cerebrospinal fluid (CSF) composition, enriched in proteins related to inflammation, immune response, complement, neuronal, and lipid metabolic pathways. Alterations in brain metabolite concentrations and in inhibitory control mechanisms and excitatory transmission were detected.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Colonic inflammation induces remodeling in CSF volume distribution, clearance, and metabolism, with derangement of the crosstalk between neurons and astrocytes, priming synaptopathy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> HIGHLIGHTS</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>An acute peripheral inflammatory trigger affects the central level by remodeling central nervous system (CNS) fluid distribution and priming early signals of synaptopathy.</li>\u0000 \u0000 <li>A single dextran sulfate sodium (DSS) challenge disrupts the circadian clock machinery and alters CNS fluid distribution, a so far neglected system, thereby impairing glymphatic clearance of waste products and indirectly altering neurotransmitter release dynamics.</li>\u0000 \u0000 <li>These combined effects ultimately impact brain function, extending to the regulation of behavior.</li>\u0000 \u0000 <li>Understanding how an intestinal inflammatory insult may derange the daily rhythm of the mechanisms controlling brain waste disposal may help identify specific groups of subjects at high risk of developing neurological disorders.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 10","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70640","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145247098","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}
引用次数: 0
Role of PCPs in diagnosing dementia in traditional Medicare and Medicare Advantage pcp在传统医疗保险和医疗优惠中诊断痴呆的作用
IF 11.1 1区 医学
Alzheimer's & Dementia Pub Date : 2025-10-09 DOI: 10.1002/alz.14559
Sidra Haye, Mireille Jacobson, Julie Zissimopoulos
{"title":"Role of PCPs in diagnosing dementia in traditional Medicare and Medicare Advantage","authors":"Sidra Haye,&nbsp;Mireille Jacobson,&nbsp;Julie Zissimopoulos","doi":"10.1002/alz.14559","DOIUrl":"10.1002/alz.14559","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>This paper quantifies how incident dementia diagnosis rates vary for similar beneficiaries in traditional Medicare (TM) and Medicare Advantage (MA) seen by the same primary care provider (PCP).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>This cohort analysis used 2016 to 2018 data for Medicare beneficiaries. Using a propensity score-matched sample of beneficiaries with similar likelihood of MA enrollment, we estimated linear probability models with PCP fixed effects of incident dementia diagnosis in 2017 for beneficiaries in MA relative to beneficiaries in TM.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Among a matched sample of 15,410,030 beneficiaries, accounting for both provider and patient characteristics, the incident dementia diagnosis rate was 0.11 percentage points lower for MA beneficiaries compared to TM beneficiaries attributed to the same PCP. MA patients were less likely to be seen by dementia specialists.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Differences in system-level factors such as access to dementia specialists is a contributing factor to differences in diagnosis rates in MA and TM.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>In this study, we quantify how incident dementia diagnosis rates vary for similar beneficiaries in TM and MA seen by the same PCP.</li>\u0000 \u0000 <li>To investigate the role of insurance design on dementia diagnosis, we examined differences in diagnosis rates for TM and MA beneficiaries seen by the same PCP.</li>\u0000 \u0000 <li>Among a matched sample of TM and MA beneficiaries with assigned PCPs in 2017, incident dementia diagnosis rates were 0.11 percentage points lower for MA beneficiaries compared to TM beneficiaries seen by the same PCP.</li>\u0000 \u0000 <li>MA patients were less likely to be seen by dementia specialists compared to TM beneficiaries seen by the same PCP.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 10","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.14559","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145247418","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}
引用次数: 0
Sex differences in vulnerability to tau pathology: Impact on cognitive decline tau病理易感性的性别差异:对认知能力下降的影响
IF 11.1 1区 医学
Alzheimer's & Dementia Pub Date : 2025-10-08 DOI: 10.1002/alz.70634
Yashar Zeighami, Cecilia Tremblay, Mahsa Dadar
{"title":"Sex differences in vulnerability to tau pathology: Impact on cognitive decline","authors":"Yashar Zeighami,&nbsp;Cecilia Tremblay,&nbsp;Mahsa Dadar","doi":"10.1002/alz.70634","DOIUrl":"10.1002/alz.70634","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Although the link between the presence of amyloid and tau pathologies, neurodegeneration, and cognitive decline in aging individuals is established, it is less clear whether there are sex differences in vulnerability to these pathologies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>A total of 1464 participants (7168 longitudinal assessments, 4.77 ± 3.78 years of follow-up) were included from the National Alzheimer's Coordinating Center (NACC) database. Longitudinal mixed effects and mediation models examined the sex differences across cognitive decline trajectories of amyloid (A), tau (T), and neurodegeneration (N) groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>A<sup>+</sup>T<sup>−</sup> males showed faster cognitive decline compared to A<sup>+</sup>T<sup>−</sup> females (<i>p</i> &lt; 0.005), whereas A<sup>+</sup>T<sup>+</sup> females showed steeper cognitive decline compared to A<sup>+</sup>T<sup>+</sup> males (<i>p</i> &lt; 0.0001). In addition, sex marginally moderated the mediating effect of tau on the relationship between amyloid and cognitive decline (<i>p</i> = 0.046).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Sex differences in vulnerability to tau pathology in the presence of amyloid can shape cognitive decline trajectories.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>A<sup>+</sup>T<sup>−</sup> males showed faster cognitive decline compared to A<sup>+</sup>T<sup>−</sup> females.</li>\u0000 \u0000 <li>A<sup>+</sup>T<sup>+</sup> females showed faster cognitive decline compared to A<sup>+</sup>T<sup>+</sup> males.</li>\u0000 \u0000 <li>Tau status significantly mediated the relationship between amyloid status and cognitive decline.</li>\u0000 \u0000 <li>Sex marginally moderated the mediating relationship between amyloid, tau, and cognitive decline.</li>\u0000 \u0000 <li>The findings point to sex differences in the impact of tau pathology on cognition.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 10","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70634","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145241369","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}
引用次数: 0
Novel differentially expressed genes and multiple biological pathways for Alzheimer's disease identified in brain tissue from African American donors 在非裔美国捐赠者的脑组织中发现了阿尔茨海默病的新差异表达基因和多种生物学途径
IF 11.1 1区 医学
Alzheimer's & Dementia Pub Date : 2025-10-08 DOI: 10.1002/alz.70629
Mark W. Logue, Adam Labadorf, Nicholas K. O'Neill, Dennis W. Dickson, Brittany N. Dugger, Margaret E. Flanagan, Matthew P. Frosch, Marla Gearing, Lee-Way Jin, Julia Kofler, Richard Mayeux, Ann McKee, Carol A. Miller, Melissa E. Murray, Peter T. Nelson, Richard J. Perrin, Julie A. Schneider, Thor D. Stein, Andrew F. Teich, Katarnut Tobunluepop, Juan C. Troncoso, Shih-Hsiu Wang, Zihan Wang, Benjamin Wolozin, Jesse Mez, Lindsay A. Farrer
{"title":"Novel differentially expressed genes and multiple biological pathways for Alzheimer's disease identified in brain tissue from African American donors","authors":"Mark W. Logue,&nbsp;Adam Labadorf,&nbsp;Nicholas K. O'Neill,&nbsp;Dennis W. Dickson,&nbsp;Brittany N. Dugger,&nbsp;Margaret E. Flanagan,&nbsp;Matthew P. Frosch,&nbsp;Marla Gearing,&nbsp;Lee-Way Jin,&nbsp;Julia Kofler,&nbsp;Richard Mayeux,&nbsp;Ann McKee,&nbsp;Carol A. Miller,&nbsp;Melissa E. Murray,&nbsp;Peter T. Nelson,&nbsp;Richard J. Perrin,&nbsp;Julie A. Schneider,&nbsp;Thor D. Stein,&nbsp;Andrew F. Teich,&nbsp;Katarnut Tobunluepop,&nbsp;Juan C. Troncoso,&nbsp;Shih-Hsiu Wang,&nbsp;Zihan Wang,&nbsp;Benjamin Wolozin,&nbsp;Jesse Mez,&nbsp;Lindsay A. Farrer","doi":"10.1002/alz.70629","DOIUrl":"10.1002/alz.70629","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Few African American (AA) donors have been included in <i>post mortem</i> Alzheimer's disease (AD) studies compared to European-ancestry (EA) individuals.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We generated transcriptome-wide bulk pre-frontal cortex (PFC) gene expression data from 125 AA donors with neuropathologically determined AD and 82 AA controls.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Transcriptome-wide significant differential expression was observed with 482 genes. The most significant, <i>ADAMTS2</i>, showed 1.52 times higher expression in AD cases (<i>p</i> = 2.96x10<sup>−8</sup>). Comparison of findings with those from a recent gene expression study of EA brain donors revealed substantial concordance, including <i>ADAMTS2</i>. Other associations not observed in EA results may be especially relevant to AD risk in the AA population. Examination of AA AD GWAS-implicated variants identified several expression quantitative trait loci.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> CONCLUSION</h3>\u0000 \u0000 <p>This first large-scale AA brain AD gene expression study identified many differentially expressed genes, including <i>ADAMTS2</i>, and supports gene expression as a molecular pathway underlying the impact of several AA AD risk variants.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>We performed the largest African American brain tissue Alzheimer's disease (AD) gene expression study.</li>\u0000 \u0000 <li>Expression differences for 482 genes, notably <i>ADAMTS2</i>, were study-wide significant.</li>\u0000 \u0000 <li>Many significant differentially expressed genes are involved in energy metabolism.</li>\u0000 \u0000 <li>Several previously known AD-associated variants in African Americans are eQTLs.</li>\u0000 \u0000 <li>These results advance knowledge of the genetic basis of AD in the AA population.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 10","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70629","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145241367","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}
引用次数: 0
Correction to “Genome-wide pleiotropy analysis of longitudinal blood pressure and harmonized cognitive performance measures” 更正“纵向血压和协调认知表现测量的全基因组多效性分析”。
IF 11.1 1区 医学
Alzheimer's & Dementia Pub Date : 2025-10-08 DOI: 10.1002/alz.70806
{"title":"Correction to “Genome-wide pleiotropy analysis of longitudinal blood pressure and harmonized cognitive performance measures”","authors":"","doi":"10.1002/alz.70806","DOIUrl":"10.1002/alz.70806","url":null,"abstract":"<p>Kang M, Ang TFA, Devine SA, et al. Genome-wide pleiotropy analysis of longitudinal blood pressure and harmonized cognitive performance measures. <i>Alzheimer's Dement</i>. 2025; 21:e70681. doi:10.1002/alz.70681</p><p>In this paper, Moonil Kang's affiliation is listed incompletely. In addition to affiliation no. 1, “Department of Medicine (Biomedical Genetics), Boston University Chobanian &amp; Avedisian School of Medicine, Boston, Massachusetts, USA,” the author should have a current affiliation, “College of Pharmacy, Sookmyung Women's University, Seoul, Republic of Korea,” as a second affiliation.</p><p>We apologize for this error.</p>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 10","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70806","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145240990","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}
引用次数: 0
Variability of longitudinal sleep monitoring in amyloid-negative and amyloid-positive cognitively unimpaired and mildly impaired older adults 纵向睡眠监测在淀粉样蛋白阴性和淀粉样蛋白阳性认知未受损和轻度受损老年人中的变异性
IF 11.1 1区 医学
Alzheimer's & Dementia Pub Date : 2025-10-08 DOI: 10.1002/alz.70761
Taylor J. Pedersen, Ruijin Lu, Cristina Toedebusch, Ashley Hess, Rachel Richardson, Allyson Quigley, Carling G. Robinson, John C. Morris, David M. Holtzman, Chengjie Xiong, Brian A. Gordon, Brendan P. Lucey
{"title":"Variability of longitudinal sleep monitoring in amyloid-negative and amyloid-positive cognitively unimpaired and mildly impaired older adults","authors":"Taylor J. Pedersen,&nbsp;Ruijin Lu,&nbsp;Cristina Toedebusch,&nbsp;Ashley Hess,&nbsp;Rachel Richardson,&nbsp;Allyson Quigley,&nbsp;Carling G. Robinson,&nbsp;John C. Morris,&nbsp;David M. Holtzman,&nbsp;Chengjie Xiong,&nbsp;Brian A. Gordon,&nbsp;Brendan P. Lucey","doi":"10.1002/alz.70761","DOIUrl":"10.1002/alz.70761","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Sleep disturbances are associated with Alzheimer's disease (AD) pathology and cognitive symptoms, but few studies have longitudinally assessed sleep, AD biomarkers, and cognition. Understanding how sleep changes over time in older adults with and without AD pathology is crucial for appropriately designing longitudinal studies of aging and AD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Sleep was measured over ≈3.5 years in older adults using self-reported questionnaires and an at-home single-channel electroencephalography (scEEG) device. Participants also underwent amyloid imaging and cognitive testing. Longitudinal change of multiple sleep parameters was determined and sample sizes estimated for future clinical trials using sleep as an outcome.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>In both amyloid groups, EEG spectral power measures demonstrated minimal longitudinal change, whereas self-reported and sleep parameters such as sleep efficiency demonstrated greater variability over time.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>This study characterized how sleep parameters change in older adults with and without AD pathology, offering important guidance for future longitudinal studies targeting sleep and neurodegeneration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Low variability in electroencephalography (EEG) spectral power metrics, including delta, theta, and alpha power.</li>\u0000 \u0000 <li>Greater variability in self-report sleep metrics, including self-reported time to fall asleep and EEG-derived metrics such as sleep duration and N2 sleep.</li>\u0000 \u0000 <li>Understanding the variability in sleep measures over time will offer important guidance for designing future longitudinal studies targeting sleep and neurodegeneration.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 10","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70761","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145241371","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}
引用次数: 0
Cholesterol-lowering drug targets reduce risk of dementia: Mendelian randomization and meta-analyses of 1 million individuals 降胆固醇药物靶点降低痴呆风险:100万人的孟德尔随机化和荟萃分析
IF 11.1 1区 医学
Alzheimer's & Dementia Pub Date : 2025-10-08 DOI: 10.1002/alz.70638
Liv Tybjærg Nordestgaard, Aimee Hanson, Eleanor Sanderson, Emma Anderson, Venexia Walker, Anne Tybjærg-Hansen, George Davey Smith, Børge G. Nordestgaard
{"title":"Cholesterol-lowering drug targets reduce risk of dementia: Mendelian randomization and meta-analyses of 1 million individuals","authors":"Liv Tybjærg Nordestgaard,&nbsp;Aimee Hanson,&nbsp;Eleanor Sanderson,&nbsp;Emma Anderson,&nbsp;Venexia Walker,&nbsp;Anne Tybjærg-Hansen,&nbsp;George Davey Smith,&nbsp;Børge G. Nordestgaard","doi":"10.1002/alz.70638","DOIUrl":"10.1002/alz.70638","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>We tested whether genetically proxied non-high-density lipoprotein cholesterol (non-HDL-C)–lowering drug targets reduce risk of all-cause dementia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We included 1,091,775 individuals from three prospective general population cohorts with individual-level data and two consortia with summary-level data. We selected genetic variants within <i>HMGCR, NPC1L1, PCSK9, ANGPTL4, LPL</i>, and <i>CETP</i> associated with non-HDL-C. These variants were used as exposures in Cox regression and one- and two-sample Mendelian randomization. Results were meta-analyzed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Meta-analysis of one-sample Mendelian randomization odds ratios per 1 mmol/L (39 mg/dL) lower non-HDL-C was 0.24 (0.18–0.31) for <i>HMGCR</i>, 0.18 (0.12–0.25) for <i>NPC1L1</i>, 0.97 (0.70–1.35) for <i>PCSK9</i>, 1.66 (0.52–5.36) for <i>ANGPTL4</i>, 1.41 (0.63–3.16) for <i>LPL</i>, and 0.30 (0.26–0.34) for <i>CETP</i>. Cox regression and two-sample Mendelian randomization results were mostly directionally consistent.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Genetic lowering of non-HDL cholesterol via <i>HMGCR, NPC1L1</i>, and <i>CETP</i> reduces the risk of dementia. This reflects the effect of lifelong differences in non-HDL cholesterol on risk of dementia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Variants in <i>HMGCR, NPC1L1</i>, and <i>CETP</i> reduce the risk of dementia via non-high-density lipoprotein cholesterol (non-HDL-C).</li>\u0000 \u0000 <li>An effect of <i>PCSK9, ANGPTL4</i>, and <i>LPL</i> variants on dementia risk cannot be excluded.</li>\u0000 \u0000 <li>This reflects the effect of lifelong lower non-HDL-C on risk of dementia.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 10","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70638","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145241375","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}
引用次数: 0
Diagnostic potential of near-infrared spectroscopy in mild cognitive impairment and neurodegenerative disorders: Implications for resource-limited settings 近红外光谱在轻度认知障碍和神经退行性疾病中的诊断潜力:对资源有限的环境的影响
IF 11.1 1区 医学
Alzheimer's & Dementia Pub Date : 2025-10-08 DOI: 10.1002/alz.70769
George Nkrumah Osei, Ansumana Bockarie, Albert Akpalu, Peter Osei-Wusu Adueming, Maxwell Hubert Antwi, Foster Appiah, Linus Kpelle, David Mawutor Donkor, David Larbi Simpong
{"title":"Diagnostic potential of near-infrared spectroscopy in mild cognitive impairment and neurodegenerative disorders: Implications for resource-limited settings","authors":"George Nkrumah Osei,&nbsp;Ansumana Bockarie,&nbsp;Albert Akpalu,&nbsp;Peter Osei-Wusu Adueming,&nbsp;Maxwell Hubert Antwi,&nbsp;Foster Appiah,&nbsp;Linus Kpelle,&nbsp;David Mawutor Donkor,&nbsp;David Larbi Simpong","doi":"10.1002/alz.70769","DOIUrl":"10.1002/alz.70769","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; BACKGROUND&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Near-infrared spectroscopy (NIRS) is emerging as a promising tool for early detection of mild cognitive impairment (MCI) and neurodegenerative diseases, especially where advanced imaging is limited.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; METHODOLOGY&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This systematic review investigates NIRS's diagnostic capabilities. Adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we conducted a comprehensive review of studies using NIRS for cognitive assessment in MCI and neurodegenerative conditions.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; RESULTS/DISCUSSION&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;NIRS effectively assesses cognitive function, identifying reduced prefrontal connectivity in MCI and subjective cognitive decline (SCD). Interestingly, while SCD patients maintain stronger brain network integrity, NIRS reveals decreased oxyhemoglobin levels in Alzheimer's disease (AD) patients’ dorsolateral prefrontal cortex. Combining NIRS with graph analysis, cognitive tasks, and machine learning significantly boosts diagnostic accuracy. Moreover, NIRS can differentiate between neurodegenerative disorders and, with concurrent electroencephalography, offers enhanced understanding of brain connectivity issues in AD. Our findings emphasize NIRS's considerable potential to improve cognitive assessment and neurodegeneration diagnosis.&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;Mild cognitive impairment (MCI) individuals show disruptions in neurovascular coupling and functional connectivity, particularly in the dorsolateral prefrontal cortex during near-infrared spectroscopy (NIRS) assessments.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Significant reductions in oxyhemoglobin (HbO&lt;sub&gt;2&lt;/sub&gt;) levels are observed in the dorsolateral prefrontal cortex of amnestic MCI (aMCI) individuals compared to healthy controls.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Individuals with subjective cognitive decline (SCD) show lower HbO&lt;sub&gt;2&lt;/sub&gt; levels than healthy individuals, while aMCI individuals show even more pronounced reductions.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;The dorsolateral prefrontal cortex is identified as a critical area for Alzheimer's disease (AD) assessment using NIRS, correlating with cognitive performance.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Differences in Broca's area activation during language tasks help distinguish behavioral variant frontotemporal dementia from AD, revealing unique cognitive p","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 10","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70769","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145241373","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}
引用次数: 0
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