The Peter Attia Drive

Snapshot · The Peter Attia Drive

#395 - Brain lipidology: understanding APOE, cholesterol homeostasis, Alzheimer's disease risk, and the effects of lipid-lowering therapies on brain health | Tom Dayspring, M.D.

Explore episode Jun 8, 2026

Where this was said

Desmosterol and 24S-hydroxycholesterol as brain biomarkers

At 1:18:20 · chapter starts 1:17:15

Tom synthesizes the desmosterol and 24S-hydroxycholesterol threads that have run through the episode. Plasma desmosterol is commercially measurable and correlates strongly with CSF desmosterol — a published study using mass spectrometry confirmed high correlation and found that low plasma desmosterol is associated with increased rates of cognitive impairment and Alzheimer's disease. If a patient is on a statin and their plasma desmosterol falls too low, that could indicate over-suppression of brain cholesterol synthesis, warranting a dose reduction or switch to a non-statin ApoB-lowering strategy. 24S-hydroxycholesterol, produced when neurons need to shed excess cholesterol, is elevated in early Alzheimer's disease and falls with statin use — another marker of improved neuronal cholesterol balance. Unfortunately, 24S-hydroxycholesterol is not yet available through commercial laboratories. Tom expresses the hope that it will become a routine clinical tool, since it would allow clinicians to simultaneously confirm adequate statin effect on brain cholesterol (falling 24S-hydroxycholesterol) and absence of over-suppression (stable desmosterol).

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