Dataset Information

The APOE ε4 exerts differential effects on familial and other subtypes of Alzheimer's disease.

ABSTRACT:

Introduction

The genetic risk effects of apolipoprotein E (APOE) on familial Alzheimer's disease (FAD) with or without gene mutations, sporadic AD (SAD), and normal controls (NC) remain unclear in the Chinese population.

Methods

In total, 15 119 subjects, including 311 FAD patients without PSEN1, PSEN2, APP, TREM2, and SORL1 pathogenic mutations (FAD [unknown]); 126 FAD patients with PSENs/APP mutations (FAD [PSENs/APP]); 7234 SAD patients; and 7448 NC were enrolled. The risk effects of APOE ε4 were analyzed across groups.

Results

The prevalence of the APOE ε4 genotype in FAD (unknown), FAD (PSENs/APP), SAD, and NC groups was 56.27%, 26.19%, 36.23%, and 19.54%, respectively. Further, the APOE ε4 positive genotype had predictive power for FAD (unknown) risk (odds ratio: 4.51, 95% confidence interval: 3.57-5.45, P < .001).

Discussion

APOE ε4 positive genotype may cause familial aggregation, and the investigation of multiple interventions targeting APOE pathological function to reduce the risk for this disease warrants attention.

SUBMITTER: Jia L

PROVIDER: S-EPMC7984370 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Publications

The APOE ε4 exerts differential effects on familial and other subtypes of Alzheimer's disease.

Jia Longfei L Xu Hui H Chen Shuoqi S Wang Xiu X Yang Jianwei J Gong Min M Wei Cuibai C Tang Yi Y Qu Qiumin Q Chu Lan L Shen Lu L Zhou Chunkui C Wang Qi Q Zhao Tan T Zhou Aihong A Li Ying Y Li Fangyu F Li Yan Y Jin Hongmei H Qin Qi Q Jiao Haishan H Li Yan Y Zhang Heng H Lyu Diyang D Shi Yuqing Y Song Yang Y Jia Jianping J

Alzheimer's & dementia : the journal of the Alzheimer's Association 20200903 12

<h4>Introduction</h4>The genetic risk effects of apolipoprotein E (APOE) on familial Alzheimer's disease (FAD) with or without gene mutations, sporadic AD (SAD), and normal controls (NC) remain unclear in the Chinese population.<h4>Methods</h4>In total, 15 119 subjects, including 311 FAD patients without PSEN1, PSEN2, APP, TREM2, and SORL1 pathogenic mutations (FAD [unknown]); 126 FAD patients with PSENs/APP mutations (FAD [PSENs/APP]); 7234 SAD patients; and 7448 NC were enrolled. The risk effe ...[more]

PMID: 32881347

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Project description:IntroductionWhile 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.MethodsTo 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).ResultsWe 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.DiscussionThis 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.HighlightsAn 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.

Dataset Information

The APOE ε4 exerts differential effects on familial and other subtypes of Alzheimer's disease.

Introduction

Methods

Results

Discussion

Publications

The APOE ε4 exerts differential effects on familial and other subtypes of Alzheimer's disease.

Similar Datasets

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