Cerebral and extracerebral cholesterol metabolism and CSF markers of Alzheimer's disease.
Level 4 - case-series / case-control
Case-control observational biomarker correlation study
PubMed 23291240 · doi:10.1016/j.bcp.2012.12.007
What was done
Researchers analyzed plasma and cerebrospinal fluid concentrations of cholesterol, cholesterol precursors (lanosterol, lathosterol, desmosterol), and elimination metabolites (24S-hydroxycholesterol, 27-hydroxycholesterol) in 107 patients with Alzheimer's disease and 86 cognitively normal controls. They evaluated correlations between these lipid markers and cerebrospinal fluid Alzheimer's biomarkers (Aβ1-42 and p-tau181), adjusting for age, gender, albumin ratio, APOE ε4 allele count, and diagnosis in multivariate regression.
What was found
The abstract reports directional associations but provides no numerical effect sizes, correlation coefficients, or p-values. In the Alzheimer's disease group, cerebrospinal fluid desmosterol, cholesterol, and 24S-hydroxycholesterol correlated with p-tau181 levels. In the control group, only cerebrospinal fluid 24S-hydroxycholesterol correlated with p-tau181. In multivariate regression, p-tau181 independently predicted cerebrospinal fluid desmosterol, cholesterol, and 24S-hydroxycholesterol concentrations. Within the Alzheimer's disease group alone, associations remained significant for cerebrospinal fluid cholesterol and 24S-hydroxycholesterol. Neither cerebrospinal fluid nor plasma concentrations of any tested compound correlated with cerebrospinal fluid Aβ1-42 levels.
Why it matters
The findings link central nervous system cholesterol synthesis and turnover specifically to tau-related neurodegeneration rather than amyloid pathology in human Alzheimer's disease.
Limits
The study is cross-sectional and observational, preventing causal inference regarding whether cholesterol dysregulation drives tau pathology or results from neurodegeneration. The abstract reports no numerical values, effect sizes, or confidence intervals. Total sample size is 193 participants.
Cited by
- context In the central nervous system, cholesterol synthesis occurs exclusively through the desmosterol pathway, making circulating desmosterol a proxy for brain cholesterol synthesis, whereas lathosterol reflects peripheral cholesterol synthesis.