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Apolipoprotein E4 mediates the association between midlife dyslipidemia and cerebral amyloid in aging women

journal contribution
posted on 2023-05-20, 05:10 authored by Szoeke, C, Goodwill, AM, Gorelik, A, Dennerstein, L, Caeyenberghs, K, Steve Simpson JRSteve Simpson JR, Eddy RoccatiEddy Roccati, Campbell, S
Cerebral amyloid-β (Aβ) plaques are the hallmark biomarker of Alzheimer's disease (AD) and are detectable decades before clinical symptoms. Modifying risk factors associated with Aβ accrual offers an opportunity for AD prevention. While midlife vascular health is linked to AD; there is minimal longitudinal evidence regarding the effect of midlife lipids on Aβ. We examined the association between midlife lipids and Aβ 20 years later. One hundred and twenty-two women had serum lipid profiles in midlife (1992, 45-57 years), and cerebral imaging, genotyping, and cognition measured 20 years later (2012/13, 66-77 years). Imaging was performed in 2012/13 via F-18 Florbetaben positron emission tomography (PET) and standard uptake value ratios (SUVR) were calculated. Lipid profiles and other predictors of high PET-SUVR levels (>1.2) were evaluated using multivariable logistic regression. Increases in low-density lipoprotein (LDL) cholesterol in midlife were associated with Aβ, adjusting for age, education, cholesterol medication, and cognition (AdjOR1.81, 95% CI 1.08-3.01, p = 0.024), but attenuated on adjustment for apolipoprotein E4 (APOE ɛ4). Aβ risk increased in women with APOE ɛ4 and midlife cholesterol >6.2 mmol/L (AdjOR9.59, 95% CI 2.94-31.31, p < 0.001), APOE ɛ4 and LDL >3.3 mmol/L (AdjOR9.00, 95% CI 2.89-28.03, p < 0.001), and APOE ɛ4 and cholesterol to high-density lipoprotein ratio ≥3.25 (AdjOR8.32, 95% CI 2.32-29.89, p < 0.001). Presence of APOE ɛ4 and midlife dyslipidemia compounded the risk for Aβ deposition, although no independent effect of midlife lipids was found. Lipid-modifying treatment in midlife could mitigate the risk of Aβ in women with a genetic predisposition for AD. To better inform prevention, future consideration should be given toward managing dyslipidemia in women carrying the APOE ɛ4 allele.

History

Publication title

Journal of Alzheimer's Disease

Volume

68

Pagination

105-114

ISSN

1387-2877

Department/School

Menzies Institute for Medical Research

Publisher

IOS Press

Place of publication

Netherlands

Rights statement

© 2019 – IOS Press and the authors. All rights reserved

Repository Status

  • Restricted

Socio-economic Objectives

Clinical health not elsewhere classified

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