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. 2024 May;20(5):3696-3704.
doi: 10.1002/alz.13811. Epub 2024 Apr 4.

Plasma oxysterols are associated with serum lipids and dementia risk in older women

Michelle M Dunk  1   2 , Stephen R Rapp  3   4 , Kathleen M Hayden  3 , Mark A Espeland  3   5   6 , Ramon Casanova  5 , JoAnn E Manson  7   8 , Aladdin H Shadyab  9   10 , Robert Wild  11 , Ira Driscoll  1   12
Affiliations

Plasma oxysterols are associated with serum lipids and dementia risk in older women

Michelle M Dunk et al. Alzheimers Dement. 2024 May.

Abstract

Introduction: Apolipoprotein E4 (APOE4) carriers' tendency toward hypercholesterolemia may contribute to Alzheimer's disease (AD) risk through oxysterols, which traverse the blood-brain barrier.

Methods: Relationships between baseline plasma oxysterols, APOE status, serum lipids, and cognitive impairment risk were examined in 328 postmenopausal women from the Women's Health Initiative Memory Study. Women were followed for 25 years or until incident dementia or cognitive impairment.

Results: Levels of 24(S)-hydroxycholesterol (24-OHC), 27-hydroxycholesterol (27-OHC), and 24-OHC/27-OHC ratio did not differ by APOE status (p's > 0.05). Higher 24-OHC and 27-OHC were associated with higher total, low density lipoprotein (LDL), non-high density lipoprotein (HDL), remnant, LDL/HDL, and total/HDL cholesterol and triglycerides (p's < 0.05). Higher 24-OHC/27-OHC was associated with greater dementia risk (hazard ratio = 1.51, 95% confidence interval:1.02-2.22), which interaction analyses revealed as significant for APOE3 and APOE4+, but not APOE2+ carriers.

Discussion: Less favorable lipid profiles were associated with higher oxysterol levels. A higher ratio of 24-OHC/27-OHC may contribute to dementia risk in APOE3 and APOE4+ carriers.

Keywords: 24‐hydroxycholesterol; 27‐hydroxycholesterol; Alzheimer's disease; Apolipoprotein E; Women's Health Initiative Memory Study; cholesterol; dementia; mild cognitive impairment; oxysterols.

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Conflict of interest statement

The authors report no conflicts of interest. Author disclosures are available in the supporting information.

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