Serum noncholesterol sterols in Alzheimer's disease: the Helsinki Businessmen Study.
Level 4 - case-series / case-control
Case-control comparison within a prospective cohort
PubMed 30102918 · doi:10.1016/j.trsl.2018.07.002
What was done
Researchers measured serum noncholesterol sterol ratios (surrogate markers for whole-body cholesterol synthesis and absorption) in home-dwelling older men from the Helsinki Businessmen Study who were not taking lipid-lowering drugs. They compared 18 men with "pure" Alzheimer's disease (AD; free of atherosclerotic cardiovascular disease) to 114 controls without AD, adjusting comparisons for age and frailty.
What was found
Standard serum lipids did not differ between groups. AD patients were older (78 ± 1 vs 74 ± 0.3 years, P < 0.001), had lower age-adjusted plasma glucose (4.8 ± 0.3 vs 5.7 ± 0.1 mmol/L, P = 0.011), and carried higher rates of APOE ε4 and frailty. After adjusting for age and frailty, synthesis markers were lower in AD versus controls (lathosterol-to-cholesterol ratio: 114 ± 12 vs 137 ± 5 × 10² µmol/mmol cholesterol, P = 0.004; desmosterol ratio also lower). The absorption marker cholestanol-to-cholesterol ratio was higher in AD, and the lathosterol/sitosterol ratio was lower (0.95 ± 0.28 vs 1.52 ± 0.11 × 10² µmol/mmol cholesterol, P = 0.027). Plasma glucose correlated negatively with cholesterol synthesis in AD, but positively in controls.
Why it matters
These findings suggest that systemic, extracerebral cholesterol metabolism and its interaction with glucose homeostasis are altered in Alzheimer's disease, shifting toward reduced synthesis and increased absorption.
Limits
The AD sample size was very small (n = 18). The cohort was entirely male and homogeneous in background. The cross-sectional design cannot establish whether altered sterol metabolism is a cause, correlate, or consequence of AD pathology.
Cited by
- partial Research data indicate that when desmosterol levels are very low, the risk of Alzheimer's disease and all-cause dementia increases.