Snapshot · The Peter Attia Drive
People with genetic CETP loss-of-function variants have lower rates of Alzheimer's disease and cognitive impairment, providing the biological rationale for testing CETP inhibitors as a neuroprotective strategy.
Where this was said
At 1:31:56 · chapter starts 1:31:00
Peter closes the pharmacology discussion with the most forward-looking topic: obicetrapib, a CETP inhibitor that inhibits the transfer of cholesterol from HDL to ApoB particles, causing HDL to enlarge and ApoA-1 to rise. The biological rationale for neuroprotection comes from genetics: people with natural CETP loss-of-function variants have lower rates of Alzheimer's disease and cognitive impairment. Pharmacologically mimicking this state could theoretically confer the same benefit [1] — Tom Dayspring "Obicetrapib, a CETP inhibitor, raises ApoA-1 and generates tiny protein-rich HDL particles that can cross the blood-brain barrier. The BROA…" 1:31:50 . Tom explains the cascade: obicetrapib enlarges HDL particles, the liver interprets the reduced free ApoA-1 as a deficiency and ramps up ApoA-1 production, and circulating ApoA-1 rises. These free ApoA-1 molecules and the tiny protein-rich HDL particles they form can cross the blood-brain barrier, fuse with brain ApoE HDL particles, and potentially convert dysfunctional APOE4 brain HDL into functional units capable of properly delivering cholesterol to neurons. The BROADWAY trial, conducted primarily for cardiovascular endpoints, measured Alzheimer's biomarkers — phosphorylated tau, amyloid-40/42 ratios, and fibrillary markers — and found movement in the right direction. New Amsterdam Pharma is now planning further trials with cognitive endpoints and possibly PET imaging. Tom and Peter are cautiously optimistic, noting that getting the timing and patient selection right — catching APOE4 carriers before irreversible pathology accumulates — will be the key challenge, citing the PREDIMED trial's early-halt success as a model for well-targeted primary prevention.
Researcher Bill Harris has concluded that an omega-3 index of 8–9% in red blood cell membranes reflects adequate omega-3 content across the body's cell membranes, though no randomized trial has proven a specific brain benefit.
Obicetrapib, a CETP inhibitor, raises ApoA-1 and generates tiny protein-rich HDL particles that can cross the blood-brain barrier. The BROADWAY trial showed movement in the right direction on phosphorylated tau, amyloid-40/42 ratios, and other Alzheimer's biomarkers — suggesting it may rescue dysfunctional APOE4 brain HDL.
Mental health challenges are nearly universal — BetterHelp's own research found the majority of Americans experiencing symptoms right now.
When applying for Medicaid to cover nursing home costs, there is a 5-year look-back period that can disqualify applicants who gave away or spent down assets.
A broken pipe filled the Bad Friends studio with what the hosts identified as hydrogen sulfide — microscopic fecal aeroparticles — that the crew denied smelling.
Fei-Fei Li's father's liver surgery performed by a da Vinci robot resulted in 10 times less blood loss than a typical open liver surgery, thanks to laparoscopic precision.
Approximately 115 million adults in the US currently have prediabetes, most of whom are unaware, according to the Lingo sponsor segment.
Drug overdose deaths in the US fell from 110,000 to 80,000 in 2024, and then to roughly 70,000 — the largest single-year drop the CDC has ever recorded.
Men's overdose death rate fell 27% in a single year, outpacing the 23% drop for women.
The steepest decline in overdose deaths was among 15–24-year-olds, whose rate fell 37%.
Fei-Fei Li observed that on a given hospital shift, nurses walk miles just to fetch medicine and supplies, illustrating a clear use case for assistive robotics in healthcare.
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