Yury Loika, Stephanie Webster, Elena Loiko, Alexander M Kulminski
{"title":"阿尔茨海默氏症患者对 tau 病理学的抵抗力和恢复力：年龄、性别和 APOE 等位基因的影响","authors":"Yury Loika, Stephanie Webster, Elena Loiko, Alexander M Kulminski","doi":"10.1002/dad2.70016","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Neurofibrillary tangles (NFTs), a hallmark of tau pathology in Alzheimer's disease (AD), accumulate in the aging brain. However, some individuals remain cognitively intact despite high Braak (III-VI) stages, which characterize NFTs' accumulation.</p><p><strong>Methods: </strong>We studied resistance and resilience to tau pathology by assessing Braak stages based on apolipoprotein E (<i>APOE</i>) alleles, sex, and age in a sample of 1932 cognitively intact individuals of European ancestry from the Alzheimer's Disease Sequencing Project (ADSP).</p><p><strong>Results: </strong>Resistance, characterized by low (0-II) Braak stages, was observed in men and women younger than 85 years of age. Resilience, indicated by high (III-VI) Braak stages, increased significantly with age in both men and women for each <i>APOE</i> allele. It became more pronounced, with the proportion of high Braak stages exceeding 50% at 85 years and older in women, irrespective of the <i>APOE</i> allele.</p><p><strong>Discussion: </strong>The identification of factors underlying resistance and resilience against AD-related pathologies is essential for promoting cognitively healthy aging.</p><p><strong>Highlights: </strong>We investigated cognitive resistance and resilience to tau pathology in Alzheimer's disease (AD).This study included individuals who were not diagnosed with AD.Braak stages 0-II and III-VI were considered as a measure of resistance and resilience, respectively.Resistance was stronger at ages younger than 85 years in non-carriers of the apolipoprotein E (<i>APOE</i>) ε4 allele.Resilience increased with age for each <i>APOE</i> allele independently of sex.At age 85 years and older, high resilience (>50%) was observed in women regardless of the <i>APOE</i> allele.</p>","PeriodicalId":53226,"journal":{"name":"Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring","volume":"16 4","pages":"e70016"},"PeriodicalIF":4.0000,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11470232/pdf/","citationCount":"0","resultStr":"{\"title\":\"Resistance and resilience to tau pathology in Alzheimer's disease: Effects of age, sex, and <i>APOE</i> alleles.\",\"authors\":\"Yury Loika, Stephanie Webster, Elena Loiko, Alexander M Kulminski\",\"doi\":\"10.1002/dad2.70016\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>Neurofibrillary tangles (NFTs), a hallmark of tau pathology in Alzheimer's disease (AD), accumulate in the aging brain. However, some individuals remain cognitively intact despite high Braak (III-VI) stages, which characterize NFTs' accumulation.</p><p><strong>Methods: </strong>We studied resistance and resilience to tau pathology by assessing Braak stages based on apolipoprotein E (<i>APOE</i>) alleles, sex, and age in a sample of 1932 cognitively intact individuals of European ancestry from the Alzheimer's Disease Sequencing Project (ADSP).</p><p><strong>Results: </strong>Resistance, characterized by low (0-II) Braak stages, was observed in men and women younger than 85 years of age. Resilience, indicated by high (III-VI) Braak stages, increased significantly with age in both men and women for each <i>APOE</i> allele. It became more pronounced, with the proportion of high Braak stages exceeding 50% at 85 years and older in women, irrespective of the <i>APOE</i> allele.</p><p><strong>Discussion: </strong>The identification of factors underlying resistance and resilience against AD-related pathologies is essential for promoting cognitively healthy aging.</p><p><strong>Highlights: </strong>We investigated cognitive resistance and resilience to tau pathology in Alzheimer's disease (AD).This study included individuals who were not diagnosed with AD.Braak stages 0-II and III-VI were considered as a measure of resistance and resilience, respectively.Resistance was stronger at ages younger than 85 years in non-carriers of the apolipoprotein E (<i>APOE</i>) ε4 allele.Resilience increased with age for each <i>APOE</i> allele independently of sex.At age 85 years and older, high resilience (>50%) was observed in women regardless of the <i>APOE</i> allele.</p>\",\"PeriodicalId\":53226,\"journal\":{\"name\":\"Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring\",\"volume\":\"16 4\",\"pages\":\"e70016\"},\"PeriodicalIF\":4.0000,\"publicationDate\":\"2024-10-12\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11470232/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1002/dad2.70016\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/10/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1002/dad2.70016","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/10/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
Resistance and resilience to tau pathology in Alzheimer's disease: Effects of age, sex, and APOE alleles.
Introduction: Neurofibrillary tangles (NFTs), a hallmark of tau pathology in Alzheimer's disease (AD), accumulate in the aging brain. However, some individuals remain cognitively intact despite high Braak (III-VI) stages, which characterize NFTs' accumulation.
Methods: We studied resistance and resilience to tau pathology by assessing Braak stages based on apolipoprotein E (APOE) alleles, sex, and age in a sample of 1932 cognitively intact individuals of European ancestry from the Alzheimer's Disease Sequencing Project (ADSP).
Results: Resistance, characterized by low (0-II) Braak stages, was observed in men and women younger than 85 years of age. Resilience, indicated by high (III-VI) Braak stages, increased significantly with age in both men and women for each APOE allele. It became more pronounced, with the proportion of high Braak stages exceeding 50% at 85 years and older in women, irrespective of the APOE allele.
Discussion: The identification of factors underlying resistance and resilience against AD-related pathologies is essential for promoting cognitively healthy aging.
Highlights: We investigated cognitive resistance and resilience to tau pathology in Alzheimer's disease (AD).This study included individuals who were not diagnosed with AD.Braak stages 0-II and III-VI were considered as a measure of resistance and resilience, respectively.Resistance was stronger at ages younger than 85 years in non-carriers of the apolipoprotein E (APOE) ε4 allele.Resilience increased with age for each APOE allele independently of sex.At age 85 years and older, high resilience (>50%) was observed in women regardless of the APOE allele.
期刊介绍：
Alzheimer''s & Dementia: Diagnosis, Assessment & Disease Monitoring (DADM) is an open access, peer-reviewed, journal from the Alzheimer''s Association® that will publish new research that reports the discovery, development and validation of instruments, technologies, algorithms, and innovative processes. Papers will cover a range of topics interested in the early and accurate detection of individuals with memory complaints and/or among asymptomatic individuals at elevated risk for various forms of memory disorders. The expectation for published papers will be to translate fundamental knowledge about the neurobiology of the disease into practical reports that describe both the conceptual and methodological aspects of the submitted scientific inquiry. Published topics will explore the development of biomarkers, surrogate markers, and conceptual/methodological challenges. Publication priority will be given to papers that 1) describe putative surrogate markers that accurately track disease progression, 2) biomarkers that fulfill international regulatory requirements, 3) reports from large, well-characterized population-based cohorts that comprise the heterogeneity and diversity of asymptomatic individuals and 4) algorithmic development that considers multi-marker arrays (e.g., integrated-omics, genetics, biofluids, imaging, etc.) and advanced computational analytics and technologies.
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