Key result
Higher serum HDL-C is associated with greater plasma Aβ oligomerization in older adults.
Why the study?
The relationship between serum HDL cholesterol and amyloid-β oligomerization, an early neurotoxic step in Alzheimer's disease, has not been directly examined in humans.
Is higher serum HDL-C associated with greater plasma amyloid-β oligomerization in older adults without dementia?
Cross-Sectional (n=170)
Is higher serum HDL-C associated with greater plasma amyloid-β oligomerization in older adults without dementia?
Answers are grounded in this paper and cite their sources.
In dementia-free older adults, higher serum HDL-C is independently associated with greater plasma Aβ oligomerization, challenging the conventional expectation of HDL-C as universally protective.
Higher high-density lipoprotein cholesterol (HDL-C) is conventionally expected to be protective, yet evidence in Alzheimer’s disease (AD) is inconsistent and may be non-linear; its relationship to amyloid-β (Aβ) oligomerization—an early, neurotoxic step in AD—has not been examined directly in humans. We investigated the association between serum HDL-C and plasma oligomerized Aβ (OAβ) in older adults without dementia. In this cross-sectional analysis of the General Lifestyle and Alzheimer’s Disease (GLAD) cohort, we studied 170 community-dwelling adults aged 65–90 years without dementia (cognitively normal or with mild cognitive impairment). Plasma OAβ was measured using the Multimer Detection System (MDS-OAβ) assay. Multiple linear regression modeled plasma OAβ on serum HDL-C, entered continuously and by category (National Cholesterol Education Program Adult Treatment Panel III scheme: < 50, 50–59, ≥ 60 mg/dL; high-HDL scheme: < 50, 50–79, ≥ 80 mg/dL), unadjusted and fully adjusted for demographic, genetic, vascular, metabolic, and nutritional covariates. Analyses were repeated within diagnostic groups, and effect modification by serum gamma-glutamyl transferase (GGT) was explored. Higher serum HDL-C was independently associated with higher plasma OAβ (adjusted B = 0.004 per mg/dL, 95% CI 0.002 to 0.007, p = 0.002). The association was graded across categories: relative to the < 50 mg/dL reference, plasma OAβ was significantly higher in the ≥ 60 mg/dL group (adjusted B = 0.141, 95% CI 0.049 to 0.234, p = 0.003) and, under the high-HDL scheme, in both the 50–79 mg/dL (B = 0.101, p = 0.014) and ≥ 80 mg/dL (B = 0.195, p = 0.014; n = 12) groups. Associations were similar in cognitively normal and mild cognitive impairment participants. The association was mainly confined to individuals with low GGT. In dementia-free older adults, higher serum HDL-C was independently associated with greater, not lesser, plasma Aβ oligomerization. Because the analysis was cross-sectional, the direction of this association is undetermined. Longitudinal studies incorporating established amyloid biomarkers and direct measures of HDL function are required.
No takes yet. Share an insight, caveat, or question.
Kim et al. (2026) conducted a cross-sectional in Without dementia (cognitively normal or with mild cognitive impairment) (n=170). Higher serum HDL-C vs. < 50 mg/dL reference was evaluated on Plasma oligomerized Aβ (OAβ) (adjusted B 0.004 per mg/dL, 95% CI 0.002 to 0.007, p=0.002). In dementia-free older adults, higher serum HDL-C was independently associated with greater plasma Aβ oligomerization (adjusted B = 0.004 per mg/dL; 95% CI 0.002 to 0.007; p = 0.002).
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: