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Apolipoprotein E4 mediates the association between midlife dyslipidemia and cerebral amyloid in aging women
journal contribution
posted on 2019-01-01, 00:00 authored by C Szoeke, A M Goodwill, A Gorelik, L Dennerstein, Karen CaeyenberghsKaren Caeyenberghs, S Simpson, E Hill, S CampbellCerebral 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 ϵ4). Aβ risk increased in women with APOE ϵ4 and midlife cholesterol >6.2 mmol/L (AdjOR9.59, 95% CI 2.94-31.31, p < 0.001), APOE ϵ4 and LDL >3.3 mmol/L (AdjOR9.00, 95% CI 2.89-28.03, p < 0.001), and APOE ϵ4 and cholesterol to high-density lipoprotein ratio ≥3.25 (AdjOR8.32, 95% CI 2.32-29.89, p < 0.001). Presence of APOE ϵ4 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 ϵ4 allele.
History
Journal
Journal of Alzheimer's diseaseVolume
68Issue
1Pagination
105 - 114Publisher
IOS PressLocation
Amsterdam, NetherlandsPublisher DOI
ISSN
1387-2877eISSN
1875-8908Language
engPublication classification
C1 Refereed article in a scholarly journalUsage metrics
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No categories selectedKeywords
Amyloid burdenapolipoproteincerebral amyloiddementiadyslipidemiapositron emission tomographypreventionserum lipid profilevascular healthScience & TechnologyLife Sciences & BiomedicineNeurosciencesNeurosciences & NeurologyDENSITY-LIPOPROTEIN CHOLESTEROLVASCULAR RISK-FACTORSSERUM-CHOLESTEROLALZHEIMERS-DISEASECOGNITIVE DECLINEE GENOTYPEBETABRAINAPOE
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