Alzheimer's & Dementia最新文献

{"title":"Transcriptomic and epigenomic profiling reveals altered responses to diesel emissions in Alzheimer's disease both in vitro and in population-based data","authors":"Liudmila Saveleva, Tereza Cervena, Claudia Mengoni, Michal Sima, Zdenek Krejcik, Kristyna Vrbova, Jitka Sikorova, Laura Mussalo, Tosca O. E. de Crom, Zuzana Šímová, Mariia Ivanova, Muhammad Ali Shahbaz, Elina Penttilä, Heikki Löppönen, Anne M. Koivisto, M. Arfan Ikram, Pasi I Jalava, Tarja Malm, Sweelin Chew, Michal Vojtisek-Lom, Jan Topinka, Rosalba Giugno, Pavel Rössner, Katja M. Kanninen","doi":"10.1002/alz.14347","DOIUrl":"https://doi.org/10.1002/alz.14347","url":null,"abstract":"Studies have correlated living close to major roads with Alzheimer's disease (AD) risk. However, the mechanisms responsible for this link remain unclear.","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"20 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142690897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"APOE ε4-associated heterogeneity of neuroimaging biomarkers across the Alzheimer's disease continuum.","authors":"Jason Mares, Gautam Kumar, Anurag Sharma, Sheina Emrani, Laura Beth McIntire, Jia Guo, Vilas Menon, Tal Nuriel","doi":"10.1002/alz.14392","DOIUrl":"https://doi.org/10.1002/alz.14392","url":null,"abstract":"<p><strong>Introduction: </strong>While the role of apolipoprotein E (APOE) ε4 in Alzheimer's disease (AD) susceptibility has been studied extensively, much less is known about the differences in disease presentation in APOE ε4 carriers versus non-carriers.</p><p><strong>Methods: </strong>To help elucidate these differences, we performed a broad analysis comparing the regional levels of six different neuroimaging biomarkers in the brains of APOE ε4 carriers versus non-carriers who participated in the Alzheimer's Disease Neuroimaging Initiative (ADNI).</p><p><strong>Results: </strong>We observed significant APOE ε4-associated heterogeneity in regional amyloid beta deposition, tau accumulation, glucose uptake, brain volume, cerebral blood flow, and white matter hyperintensities within each AD diagnostic group. We also observed important APOE ε4-associated differences in cognitively unimpaired individuals who converted to mild cognitive impairment/AD versus those who did not convert.</p><p><strong>Discussion: </strong>This observed heterogeneity in neuroimaging biomarkers between APOE ε4 carriers versus non-carriers may have important implications regarding the prevention, diagnosis, and treatment of AD in different subpopulations.</p><p><strong>Highlights: </strong>An extensive study was performed on the apolipoprotein E (APOE) ε4-associated heterogeneity in neuroimaging biomarkers from the Alzheimer's Disease Neuroimaging Initiative. Robust APOE ε4-associated increases in amyloid beta (Aβ) deposition throughout the brain, in every diagnostic group, were observed. APOE ε4-associated increases in tau pathology, decreases in glucose uptake, and increases in brain atrophy, which expand in regional scope and magnitude with disease progression, were observed. Significant sex- and age-related differences in APOE ε4-associated neuroimaging biomarker heterogeneity, with overall increases in pathological presentation in female APOE ε4 carriers, were observed. Regional differences in Aβ deposition, tau accumulation, glucose uptake, ventricle size, and white matter hyperintensities were observed in cognitively normal participants who converted to mild cognitive impairment/Alzheimer's disease, which may hold potential predictive value.</p>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142685804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Midlife and late-life environmental exposures on dementia risk in the Wisconsin Longitudinal Study: The modifying effects of ApoE","authors":"Victoria J. Williams, Ralph Trane, Kamil Sicinski, Pamela Herd, Michal Engelman, Sanjay Asthana","doi":"10.1002/alz.14216","DOIUrl":"https://doi.org/10.1002/alz.14216","url":null,"abstract":"Late-life air pollution exposure is associated with an increased risk for dementia, with this effect exacerbated among apolipoprotein E-4 (ApoE-4) carriers. However, whether midlife occupational exposures likewise influence dementia outcomes, and varies as a function of ApoE-4 status is unknown.","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"16 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142684538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The contribution of cerebral small vessel disease in idiopathic normal pressure hydrocephalus: Insights from a prospective cohort study","authors":"Hanlin Cai, Keru Huang, Feng Yang, Jiaojiang He, Na Hu, Hui Gao, Shiyu Feng, Linyuan Qin, Ruihan Wang, Xiyue Yang, Shan Wang, Qian Liao, Yi Liu, Dong Zhou, Liangxue Zhou, Zilong Hao, Qin Chen","doi":"10.1002/alz.14395","DOIUrl":"https://doi.org/10.1002/alz.14395","url":null,"abstract":"Idiopathic normal pressure hydrocephalus (iNPH) and cerebral small vessel disease (CVSD) are age-related diseases, but their prevalence and clinical relationship are unclear.","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"67 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142684593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma pTau217 ratio predicts continuous regional brain tau accumulation in amyloid-positive early Alzheimer's disease.","authors":"Viswanath Devanarayan, Arnaud Charil, Kanta Horie, Thomas Doherty, Daniel A Llano, Erica Andreozzi, Pallavi Sachdev, Yuanqing Ye, Leema Krishna Murali, Jin Zhou, Larisa Reyderman, Harald Hampel, Lynn D Kramer, Shobha Dhadda, Michael C Irizarry","doi":"10.1002/alz.14411","DOIUrl":"https://doi.org/10.1002/alz.14411","url":null,"abstract":"<p><strong>Background: </strong>This study examines whether phosphorylated plasma Tau217 ratio (pTau217R) can predict tau accumulation in different brain regions, as measured by positron emission tomography (PET) standardized uptake value ratio (SUVR), for staging Alzheimer's disease (AD).</p><p><strong>Methods: </strong>Plasma pTau217R was measured using immunoprecipitation-mass spectrometry. Models for predicting tau PET SUVR, developed with 144 early AD individuals using [¹⁸F]MK6240, were validated in two validation sets, VS1 (98 early AD) and VS2 (47 preclinical/early AD with a different tracer, flortaucipir (Tauvid)), all amyloid-beta positive (Aβ+).</p><p><strong>Results: </strong>The pTau217R-based model predicted tau levels up to an SUVR of 2 in multiple brain regions, effectively assessing tau status at different tau levels with receiver operating characteristic (ROC) curve areas of 0.84-0.95 in VS1 and 0.71-0.88 in VS2 (using a different tracer). It reduced PET scan needs by 65% while maintaining 95% sensitivity.</p><p><strong>Discussion: </strong>PTau217R reliably predicts regional tau accumulation in early AD, reducing reliance on tau PET scans and broadening its clinical application.</p><p><strong>Clinical trial registration number: </strong>NCT03887455 (ClarityAD) HIGHLIGHTS: Developed a model using plasma pTau217R to predict tau levels across brain regions. pTau217R model outperformed models based on clinical, MRI, and other blood biomarkers. The model reliably predicted tau levels exceeding tau positivity and higher thresholds. Screening with pTau217R could reduce tau PET scans by 65% at 95% sensitivity. pTau217R model aids in disease staging and monitoring in early AD.</p>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142685806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Benchmarking of a multi-biomarker low-volume panel for Alzheimer's disease and related dementia research","authors":"Laura Ibanez, Menghan Liu, Aleksandra Beric, Jigyasha Timsina, Pat Kohlfeld, Kristy Bergmann, Joey Lowery, Nick Sykora, Brenda Sanchez-Montejo, Will Brock, John P. Budde, Randall J. Bateman, Nicolas Barthelemy, Suzanne E. Schindler, David M. Holtzman, Tammie L. S. Benzinger, Chengjie Xiong, Rawan Tarawneh, Krista Moulder, John C. Morris, Yun Ju Sung, Carlos Cruchaga","doi":"10.1002/alz.14413","DOIUrl":"https://doi.org/10.1002/alz.14413","url":null,"abstract":"In the research setting, obtaining accurate established biomarker measurements and maximizing use of the precious samples is key. Accurate technologies are available for Alzheimer's disease (AD), but no platform can measure all the established and emerging biomarkers in one run. The NUcleic acid Linked Immuno-Sandwich Assay (NULISA) is a technology that requires 15 µL of sample to measure more than 100 analytes.","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"7 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142684587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biological validation of peak-width of skeletonized mean diffusivity as a VCID biomarker: The MarkVCID Consortium","authors":"Alison M. Luckey, Saptaparni Ghosh, Chen-Pin Wang, Alexa Beiser, Rebecca Bernal, Zhiguang Li, Djass Mbangdadji, Elyas Fadaee, Haykel Snoussi, Angel Gabriel Velarde Dediós, Hector A. Trevino, Monica Goss, Laura J. Hillmer, Christopher E. Bauer, Adam M. Staffaroni, Lara Stables, Marilyn Albert, Jayandra J. Himali, Thomas H. Mosley, Lars Forsberg, Vilmundur Guðnason, Baljeet Singh, Herpreet Singh, Kristin Schwab, Joel H. Kramer, Gary A. Rosenberg, Karl G. Helmer, Steven M. Greenberg, Mohamad Habes, Danny J. J. Wang, Brian T. Gold, Hanzhang Lu, Arvind Caprihan, Myriam Fornage, Lenore J. Launer, Konstantinos Arfanakis, Sudha Seshadri, Charles DeCarli, Pauline Maillard, Claudia L. Satizabal","doi":"10.1002/alz.14345","DOIUrl":"https://doi.org/10.1002/alz.14345","url":null,"abstract":"Peak-width of skeletonized mean diffusivity (PSMD), a neuroimaging marker of cerebral small vessel disease (SVD), has shown excellent instrumental properties. Here, we extend our work to perform a biological validation of PSMD.","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"129 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142678608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Centiloid recommendations for clinical context-of-use from the AMYPAD consortium","authors":"Lyduine E. Collij, Ariane Bollack, Renaud La Joie, Mahnaz Shekari, Santiago Bullich, Núria Roé-Vellvé, Norman Koglin, Aleksandar Jovalekic, David Valléz Garciá, Alexander Drzezga, Valentina Garibotto, Andrew W. Stephens, Mark Battle, Christopher Buckley, Frederik Barkhof, Gill Farrar, Juan Domingo Gispert","doi":"10.1002/alz.14336","DOIUrl":"https://doi.org/10.1002/alz.14336","url":null,"abstract":"Amyloid-PET quantification through the tracer-independent Centiloid (CL) scale has emerged as an essential tool for the accurate measurement of amyloid-β (Aβ) pathology in Alzheimer's disease (AD) patients. The AMYPAD consortium set out to integrate existing literature and recent work from the consortium to provide clinical context-of-use recommendations for the CL scale. Compared to histopathology, visual reads, and cerebrospinal fluid, CL quantification accurately reflects the amount of AD pathology. With high certainty, a CL value below 10 excludes the presence of Aβ pathology, while a value above 30 corresponds well with pathological amounts. Values falling in between these two cutoffs (“intermediate range”) are related to an increased risk of disease progression. Together, CL quantification is a valuable adjunct to visual assessments of amyloid-PET images. An abnormal amyloid biomarker assessment is a key criterion to determine eligibility for anti-amyloid disease-modifying therapies, and amyloid-PET quantification can add further value by precisely monitoring amyloid clearance, and hence guiding patient management decisions.","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"12 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142672951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Counseling and disclosure practices in predictive Alzheimer's disease diagnostics: A scoping review.","authors":"Julia Perry, Katrin Radenbach, Katharina Geschke, Ayda Rostamzadeh","doi":"10.1002/alz.14365","DOIUrl":"10.1002/alz.14365","url":null,"abstract":"<p><p>New possibilities of biomarker-based predictive technologies for Alzheimer's disease (AD) have become more reliable as well as more accessible. Standardized clinical recommendations and guidance for counseling and disclosure in this context are not yet well developed. Our scoping review identified publications from database searches in PubMed, PsycINFO, LIVIVO, and Web of Science. Inclusion criteria were: (1) information or counseling, (2) biomarkers and a type of cognitive impairment or AD, and (3) published between 2005 and 2024. We identified 63 articles and synthesized them along the categories of staged information provision: pre-test counseling, disclosure, and post-disclosure follow-up. Most publications referred to the context of disclosure (48), followed by pre-test counseling (33), and post-disclosure follow-up (31). Some publications referred to all stages of counseling (17). Our findings highlight the need to further develop and specify comprehensive and standardized guidelines for counseling, disclosure, and post-disclosure follow-up in the context of AD biomarker testing. HIGHLIGHTS: New possibilities of biomarker-based predictive technologies for Alzheimer's disease (AD) have become more reliable and also more accessible. However, clinical recommendations and guidance for counseling and disclosure in the context of AD biomarker testing are currently not well developed. We carried out a scoping review with the aim to generate an overview of the scientific literature and guidance available regarding counseling, biomarker test result and dementia risk disclosure, and clinical management prior to and in the course of a biomarker-based diagnosis in early stages of AD. We identified 63 relevant articles. Most publications referred to the context of disclosure (48), followed by pre-test counseling (33), and post-disclosure follow-up (31). Some publications referred to all stages of counseling (17). Our findings highlight the urgent need for national and international consensus guidelines for comprehensive and staged counseling and disclosure practices. While most publications identify relevant ethical challenges posed for counseling practices in the context of AD biomarker testing, they rarely present any practical recommendations for clinicians, on how and what to counsel on a concrete level.</p>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142666194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma p-tau181 and GFAP reflect 7T MR-derived changes in Alzheimer's disease: A longitudinal study of structural and functional MRI and MRS.","authors":"Laura Göschel, Andrea Dell'Orco, Ariane Fillmer, Semiha Aydin, Bernd Ittermann, Layla Riemann, Sylvain Lehmann, Stefan Cano, Jeanette Melin, Leslie Pendrill, Patty L Hoede, Charlotte E Teunissen, Claudia Schwarz, Ulrike Grittner, Péter Körtvélyessy, Agnes Flöel","doi":"10.1002/alz.14318","DOIUrl":"10.1002/alz.14318","url":null,"abstract":"<p><strong>Background: </strong>Associations between longitudinal changes of plasma biomarkers and cerebral magnetic resonance (MR)-derived measurements in Alzheimer's disease (AD) remain unclear.</p><p><strong>Methods: </strong>In a study population (n = 127) of healthy older adults and patients within the AD continuum, we examined associations between longitudinal plasma amyloid beta 42/40 ratio, tau phosphorylated at threonine 181 (p-tau181), glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), and 7T structural and functional MR imaging and spectroscopy using linear mixed models.</p><p><strong>Results: </strong>Increases in both p-tau181 and GFAP showed the strongest associations to 7T MR-derived measurements, particularly with decreasing parietal cortical thickness, decreasing connectivity of the salience network, and increasing neuroinflammation as determined by MR spectroscopy (MRS) myo-inositol.</p><p><strong>Discussion: </strong>Both plasma p-tau181 and GFAP appear to reflect disease progression, as indicated by 7T MR-derived brain changes which are not limited to areas known to be affected by tau pathology and neuroinflammation measured by MRS myo-inositol, respectively.</p><p><strong>Highlights: </strong>This study leverages high-resolution 7T magnetic resonance (MR) imaging and MR spectroscopy (MRS) for Alzheimer's disease (AD) plasma biomarker insights. Tau phosphorylated at threonine 181 (p-tau181) and glial fibrillary acidic protein (GFAP) showed the largest changes over time, particularly in the AD group. p-tau181 and GFAP are robust in reflecting 7T MR-based changes in AD. The strongest associations were for frontal/parietal MR changes and MRS neuroinflammation.</p>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142666296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}