Quote · 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.
Where this was said
Desmosterol and 24S-hydroxycholesterol as brain biomarkers
At 1:17:50 · 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 [1] — Tom Dayspring "24S-hydroxycholesterol as neuronal distress marker: Elevated plasma 24S-hydroxycholesterol signals that neurons are excreting excess choles…" 1:06:40 . 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).
Plasma desmosterol correlates highly with cerebrospinal fluid desmosterol and brain tissue cholesterol synthesis, making it a measurable blood biomarker of brain cholesterol production; low levels are associated with higher rates of cognitive impairment.
