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

Michelle M Dunk; Stephen R Rapp; Kathleen M Hayden; Mark A Espeland; Ramon Casanova; JoAnn E Manson; Aladdin H Shadyab; Robert Wild; Ira Driscoll

doi:10.1002/alz.13811

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

Alzheimers Dement. 2024 Apr 4. doi: 10.1002/alz.13811. Online ahead of print.

Authors

Michelle M Dunk^{1

2}, Stephen R Rapp^{3

4}, Kathleen M Hayden³, Mark A Espeland^{3

5

6}, Ramon Casanova⁵, JoAnn E Manson^{7

8}, Aladdin H Shadyab^{9

10}, Robert Wild¹¹, Ira Driscoll^{1

12}

Affiliations

¹ Department of Psychology, University of Wisconsin - Milwaukee, Milwaukee, Wisconsin, USA.
² Aging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
³ Department of Social Sciences and Health Policy, Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
⁴ Department of Psychiatry and Behavioral Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
⁵ Department of Biostatistics and Data Science, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
⁶ Sticht Center for Healthy Aging and Alzheimer's Prevention, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
⁷ Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
⁸ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
⁹ Herbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, La Jolla, California, USA.
¹⁰ Division of Geriatrics, Gerontology, and Palliative Care, Department of Medicine, University of California San Diego, La Jolla, California, USA.
¹¹ Departments of Obstetrics and Gynecology, Biostatistics and Epidemiology, Oklahoma University Health Sciences Center, Oklahoma City, Oklahoma, USA.
¹² Wisconsin Alzheimer's Disease Research Center, University of Wisconsin-Madison, Madison, Wisconsin, USA.

PMID: 38574442
DOI: 10.1002/alz.13811

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.

Abstract

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