APOE and amyloid-tau pathology in cognitively unimpaired older adults.

IF 4.4 Q1 CLINICAL NEUROLOGY

Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring Pub Date : 2026-09-27 eCollection Date: 2026-07-01 DOI:10.1002/dad2.70496

Carlos Albarrán Morillo, Lukai Zheng, Elham Ghanbarian, Babak Khorsand, Crystal M Glover, Joshua D Grill, S Ahmad Sajjadi, Ali Ezzati

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引用次数: 0

Abstract

Introduction: Apolipoprotein E (APOE) genotype shows well-established dose-dependent associations with higher amyloid in cognitively unimpaired (CU) adults. In contrast, associations with tau burden and cognition are less well characterized.

Methods: We performed a cross-sectional analysis of CU participants from the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4), Alzheimer's Disease Neuroimaging Initiative (ADNI), Wisconsin Registry for Alzheimer's Prevention (WRAP), and National Alzheimer's Coordinating Center (NACC) within the harmonized multi-cohort Alzheimer's Disease Sequencing Project Phenotype Harmonization Consortium (ADSP-PHC) data. A total of 4380 CU participants were included with APOE genotype, amyloid PET, and cognitive data (memory, language, executive, and visuospatial function), including a subset of 758 with tau PET imaging.

Results: Compared with ε33, ε24 (β = 18.340), ε34 (β = 23.850), and ε44 (β = 44.820) showed higher amyloid burden (all p < .001). Similarly, ε24 (OR = 4.180), ε34 (OR = 4.540), and ε44 (OR = 14.150) had higher odds of amyloid positivity (all p < .001). After adjustment for amyloid burden, ε4 carriers had higher tau burden in the entorhinal cortex (β = 0.026; false discovery rate [FDR] -adjusted p = 0.041) and amygdala (β = 0.040; FDR-adjusted p = 0.003). Higher tau burden was associated with lower memory (β = -0.439; FDR-adjusted p = 0.012) and language performance (β = -0.610; FDR-adjusted p = 0.020).

Discussion: APOE ε4 showed a strong dose-dependent association with amyloid, with the highest levels observed among ε4 homozygotes. Associations between APOE and global tau were more modest and appeared to be driven mainly by ε4 homozygotes, while regional analyses showed localized APOE ε4-related associations in medial temporal regions. Independently, higher tau was associated with lower memory and language performance.

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认知功能未受损老年人的APOE和淀粉样蛋白病理。

载脂蛋白E （APOE）基因型在认知功能未受损（CU）成人中显示出与较高淀粉样蛋白的剂量依赖关系。相比之下，与tau负担和认知之间的联系则不太清楚。方法：我们对来自无症状阿尔茨海默病抗淀粉样蛋白治疗（A4）、阿尔茨海默病神经影像学倡议（ADNI）、威斯康星州阿尔茨海默病预防登记处（WRAP）和国家阿尔茨海默病协调中心（NACC）的CU参与者进行了横断面分析，这些参与者来自统一的多队列阿尔茨海默病测序项目表型协调联盟（ADSP-PHC）数据。共有4380名CU参与者被纳入APOE基因型，淀粉样蛋白PET和认知数据（记忆，语言，执行和视觉空间功能），包括758名tau PET成像。结果：与ε33相比，ε24 （β = 18.340）、ε34 （β = 23.850）和ε44 （β = 44.820）的淀粉样蛋白负荷较高（p < 0.001）。同样，ε24 （OR = 4.180）、ε34 （OR = 4.540）和ε44 （OR = 14.150）的淀粉样蛋白阳性几率较高（p < 0.001）。经淀粉样蛋白负荷调整后，ε4携带者在内嗅皮层（β = 0.026，假发现率[FDR]调整p = 0.041）和杏仁核（β = 0.040， FDR调整p = 0.003）的tau负荷较高。较高的tau负担与较低的记忆力（β = -0.439；经fdr调整的p = 0.012）和语言表现（β = -0.610；经fdr调整的p = 0.020）相关。讨论：APOE ε4与淀粉样蛋白表现出强烈的剂量依赖性，在ε4纯合子中观察到最高水平。APOE与整体tau之间的关联较为温和，似乎主要由ε4纯合子驱动，而区域分析显示，APOE ε4与内侧颞区相关。独立地说，较高的tau蛋白与较低的记忆力和语言表现有关。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring Medicine-Psychiatry and Mental Health

CiteScore

7.80

自引率

7.50%

发文量

101

审稿时长

8 weeks

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.