Peter Attia MD395 – Brain lipidology: understanding APOE, cholesterol homeostasis, Alzheimer’s disease, & more
Episode Details
EPISODE INFO
- Released
- June 9, 2026
- Duration
- 1h 44m
- Channel
- Peter Attia MD
- Watch on YouTube
- ▶ Open ↗
EPISODE DESCRIPTION
Tom Dayspring is a world-renowned lipidologist and one of the most thoughtful teachers in the field of lipid metabolism. In this episode, Tom returns to The Drive for a deep dive into the relationship between lipids and brain health, beginning with the fundamentals of cholesterol transport before exploring why the brain’s cholesterol system operates almost entirely independently from the rest of the body. Tom examines the roles of apoB, apoA-I, and especially apoE in cholesterol homeostasis, discusses how APOE genotype influences Alzheimer’s disease risk, and unpacks the complex links between cholesterol metabolism, amyloid, and tau pathology. He also reviews what is currently known—and still uncertain—about the effects of statins, ezetimibe, omega-3 fatty acids, and emerging CETP inhibitors on brain health and neurodegenerative disease risk. View show notes here: https://peterattiamd.com/tomdayspring8/ Become a member to receive exclusive content: https://peterattiamd.com/subscribe/ Sign up to receive Peter's email newsletter: https://peterattiamd.com/newsletter/ 0:00:00-Intro 0:00:11-The fundamentals of cholesterol transport in the body, and how peripheral cholesterol metabolism differs from cholesterol handling in the brain 0:09:27-How cholesterol is transported through plasma and stored within cells, and why lowering LDL cholesterol does not deplete the body or brain of cholesterol 0:17:57-How apoB particles drive atherosclerosis, why lowering lipids matters, and the factors that influence individual cardiovascular risk 0:27:27-How the brain produces and transports its own cholesterol using apoE lipoproteins independently of circulating cholesterol and apoB-containing lipoproteins 0:37:44-How apoB structure influences LDL receptor binding and LDL clearance 0:40:37-How neurons acquire cholesterol from apoE-containing lipoproteins and why desmosterol serves as a unique marker of cholesterol synthesis in the brain 0:47:50-The difference between the APOE gene and the apoE protein, the major APOE genotypes found in humans, and how APOE4 influences Alzheimer’s disease risk 0:52:49-HDL function beyond cholesterol: immune function, protein cargo, and communication with the brain 0:57:44-How APOE4-associated defects in brain cholesterol transport may promote Alzheimer’s disease: amyloid production, neuronal cholesterol homeostasis, and cholesterol clearance 1:09:13-Statins and brain health: reviewing the evidence of the potential impact of statins on cognition and Alzheimer’s disease risk 1:17:35-Desmosterol and 24S-hydroxycholesterol as biomarkers of brain cholesterol metabolism and statin effects 1:19:49-Possible cognitive benefits of ezetimibe beyond lowering apoB 1:23:57-EPA, DHA, and the evidence for omega-3 fatty acids in brain health 1:32:11-Obicetrapib: an emerging CETP inhibitor with potential implications for both cardiovascular and brain health -------- About: The Peter Attia Drive is a deep-dive podcast focusing on maximizing longevity, and all that goes into that from physical to cognitive to emotional health. With over 90 million episodes downloaded, it features topics including exercise, nutritional biochemistry, cardiovascular disease, Alzheimer’s disease, cancer, mental health, and much more. Peter Attia is the founder of Early Medical, a medical practice that applies the principles of Medicine 3.0 to patients with the goal of lengthening their lifespan and simultaneously improving their healthspan. Learn more: https://peterattiamd.com Connect with Peter on: Facebook: http://bit.ly/PeterAttiaMDFB Twitter: http://bit.ly/PeterAttiaMDTW Instagram: http://bit.ly/PeterAttiaMDIG Subscribe to The Drive: Apple Podcast: http://bit.ly/TheDriveApplePodcasts Overcast: http://bit.ly/TheDriveOvercast Spotify: http://bit.ly/TheDriveSpotify Google Podcasts: http://bit.ly/TheDriveGoogle Disclaimer: This podcast is for general informational purposes only and does not constitute the practice of medicine, nursing, or other professional healthcare services, including the giving of medical advice. No doctor-patient relationship is formed. The use of this information and the materials linked to this podcast is at the user's own risk. The content on this podcast is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Users should not disregard or delay in obtaining medical advice for any medical condition they have, and they should seek the assistance of their healthcare professionals for any such conditions. I take conflicts of interest very seriously. For all of my disclosures and the companies I invest in or advise, please visit my website where I keep an up-to-date and active list of such companies. For a full list of our registered and unregistered trademarks, trade names, and service marks, please review our Terms of Use: https://peterattiamd.com/terms-of-use/
SPEAKERS
Peter Attia
hostPhysician and host of The Drive podcast, focused on longevity and preventive medicine.
Tom Dayspring
guestLipidology expert known for deep mechanistic and clinical discussions of cholesterol, apoB/apoE, and cardiometabolic therapeutics.
EPISODE SUMMARY
In this episode of Peter Attia MD, featuring Peter Attia and Tom Dayspring, 395 – Brain lipidology: understanding APOE, cholesterol homeostasis, Alzheimer’s disease, & more explores brain Cholesterol Works Separately From Blood Lipids, and APOE4 Disrupts It Dayspring explains that peripheral cholesterol travels in apoB and apoA lipoproteins, that most body cholesterol sits in cells rather than plasma, and that lowering plasma LDL does not meaningfully deplete body or brain cholesterol.
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