Hussein N. Yassine
@yassinelab1.bsky.social
📤 138
📥 175
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Professor of Neurology. Humanist. Mentor. Alzheimer’s disease research.
Join USC CPBH SPARK and help support research on how lifestyle and health may influence brain aging and Alzheimer’s disease risk. There is no cost to join, and SPARK includes privacy protections. All participants receive a personalized lifestyle and health summary.
redcap.link/CPBH.SPARK
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SPARK (Supporting Progress in Alzheimer's Research and Knowledge) is a program that connects participants with research opportunities and helps advance discoveries in Alzheimer's disease and dementia. Your de-identified survey responses also contribute to research, ensuring your privacy while enabling researchers to better understand the factors that influence brain health.
https://redcap.link/CPBH.SPARK
about 14 hours ago
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The Amyloid Hypothesis of Alzheimer's Disease: What is Validated, What is Missed, and What Comes Next
open.substack.com/pub/hyassine...
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The Amyloid Hypothesis of Alzheimer's Disease: What is Validated, What is Missed, and What Comes Next
One of the most debated hypotheses in modern medicine
https://open.substack.com/pub/hyassine/p/the-amyloid-hypothesis-of-alzheimers?utm_campaign=post-expanded-share&utm_medium=web
7 days ago
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Hormone Replacement Therapy, Brain Health, and APOE4
open.substack.com/pub/hyassine...
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Hormone Replacement Therapy, Brain Health, and APOE4
Understanding the benefits, risks, and unanswered questions surrounding hormone therapy and cognitive aging.
https://open.substack.com/pub/hyassine/p/hormone-replacement-therapy-brain?utm_campaign=post-expanded-share&utm_medium=web
14 days ago
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To Statin or Not To Statin for Alzheimer's?
open.substack.com/pub/hyassine...
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To Statin or Not To Statin for Alzheimer's?
Why the best case for statins in APOE4 is vascular, not “Alzheimer’s treatment”
https://open.substack.com/pub/hyassine/p/to-statin-or-not-to-statin-for-alzheimers?utm_campaign=post-expanded-share&utm_medium=web
27 days ago
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cPLA2 and the Synapse
open.substack.com/pub/hyassine...
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cPLA2 and the Synapse
New human data on an inflammatory enzyme linked to cognitive impairment in Alzheimer's disease
https://open.substack.com/pub/hyassine/p/cpla2-and-the-synapse?utm_campaign=post-expanded-share&utm_medium=web
about 1 month ago
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Ketosis, weight loss, and the APOE ε4 brain
open.substack.com/pub/hyassine...
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Ketosis, weight loss, and the APOE ε4 brain
A 70-year-old man came for a second opinion on optimizing brain health.
https://open.substack.com/pub/hyassine/p/ketosis-weight-loss-and-the-apoe?utm_campaign=post-expanded-share&utm_medium=web
about 1 month ago
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Blood Pressure and Brain Health: Why When Matters as Much as How Much
open.substack.com/pub/hyassine...
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Blood Pressure and Brain Health: Why When Matters as Much as How Much
I recently saw an 85-year-old man in clinic because his memory has been declining.
https://open.substack.com/pub/hyassine/p/blood-pressure-and-brain-health-why?utm_campaign=post-expanded-share&utm_medium=web
about 2 months ago
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Blood-Based Biomarkers for Alzheimer’s Disease: What They Reveal—and What Remains Uncertain
open.substack.com/pub/hyassine...
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Blood-Based Biomarkers for Alzheimer’s Disease: What They Reveal—and What Remains Uncertain
A 55-year-old woman sits across from me in clinic.
https://open.substack.com/pub/hyassine/p/blood-based-biomarkers-for-alzheimers?utm_campaign=post-expanded-share&utm_medium=web
about 2 months ago
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Why the New Food Pyramid Matters—Especially for the Brain
open.substack.com/pub/hyassine...
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Why the New Food Pyramid Matters—Especially for the Brain
The new dietary guidelines arrive at a moment when nutrition science is finally catching up with biology.
https://open.substack.com/pub/hyassine/p/why-the-new-food-pyramid-mattersespecially?utm_campaign=post-expanded-share&utm_medium=web
2 months ago
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Long Way to cPLA2: How a Nutrition Question Changed Our View of Alzheimer’s
open.substack.com/pub/hyassine...
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Long Way to cPLA2: How a Nutrition Question Changed Our View of Alzheimer’s
As we enter a new year, I want to wish you a healthy 2026 and share a bit of the story behind our most recent paper (published online today).
https://open.substack.com/pub/hyassine/p/long-way-to-cpla2-how-a-nutrition?utm_campaign=post-expanded-share&utm_medium=web
2 months ago
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The Bend in the Curve: APOE ε4, Cognition, and Prevention APOE ε4 raises dementia risk, but it isn’t destiny. Last post before the holidays, and Merry Christmas to you all.
open.substack.com/pub/hyassine...
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The Bend in the Curve: APOE ε4, Cognition, and Prevention
Merry Christmas, everyone.
https://open.substack.com/pub/hyassine/p/the-bend-in-the-curve-apoe-4-cognition?utm_campaign=post-expanded-share&utm_medium=web
3 months ago
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From the Supplement Aisle to Evolving Science: Rethinking Omega-3s, Krill Oil, and Brain Health
open.substack.com/pub/hyassine...
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From the Supplement Aisle to Evolving Science: Rethinking Omega-3s, Krill Oil, and Brain Health
I was at Costco recently, walking through the supplement aisle, when I noticed how much space is now devoted to krill oil and other omega-3 products.
https://open.substack.com/pub/hyassine/p/from-the-supplement-aisle-to-evolving?utm_campaign=post-expanded-share&utm_medium=web
3 months ago
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Could a Shingles Vaccine Protect Your Brain? The Evidence Is Getting Hard to Ignore
open.substack.com/pub/hyassine...
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Could a Shingles Vaccine Protect Your Brain? The Evidence Is Getting Hard to Ignore
This story starts with a simple but powerful idea: the brain’s immune cells can burn out. In Alzheimer’s disease, the main cleanup crew—microglia—spend years immersed in low-grade inflammation, consta...
https://open.substack.com/pub/hyassine/p/could-a-shingles-vaccine-protect?r=5ha6ys&utm_campaign=post&utm_medium=web&showWelcomeOnShare=false
3 months ago
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Semaglutide trial failures in Alzheimer's: missed opportunities to test the metabolic hypothesis of AD
open.substack.com/pub/hyassine...
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Semaglutide trial failures in Alzheimer's: missed opportunities to test the metabolic hypothesis of AD
For almost a decade, scientists have been intrigued by the possibility that Alzheimer’s disease might be, at least in part, a disorder of brain energy failure. The brain runs on glucose, and many earl...
https://open.substack.com/pub/hyassine/p/semaglutide-trial-failures-in-alzheimers?r=5ha6ys&utm_campaign=post&utm_medium=web&showWelcomeOnShare=false
4 months ago
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High dose omega-3s in end stage renal disease: what do we learn from the PISCES trial?
open.substack.com/pub/hyassine...
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High dose omega-3s in end stage renal disease: what do we learn from the PISCES trial?
In the PISCES trial, 1,228 adults on long-term hemodialysis in Canada and Australia were randomized to receive either 4 grams per day of fish oil (1.6 g EPA + 0.8 g DHA) or a corn-oil placebo for 3.5 ...
https://open.substack.com/pub/hyassine/p/high-dose-omega-3s-in-end-stage-renal?r=5ha6ys&utm_campaign=post&utm_medium=web&showWelcomeOnShare=false
4 months ago
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APOE-directed therapeutics in AD: My first substack post:
open.substack.com/pub/hyassine...
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ApoE directed Therapeutics in Alzheimer's disease, SFN 2025
Alzheimer’s disease has historically been viewed through the lens of amyloid plaques and tau tangles, but accumulating evidence shows that these features alone cannot fully explain why some individual...
https://open.substack.com/pub/hyassine/p/apoe-directed-therapeutics-in-alzheimers?r=5ha6ys&utm_campaign=post&utm_medium=web&showWelcomeOnShare=true
4 months ago
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www.theguardian.com/us-news/2025...
A good analysis by the Guardian explaining how associations are often not causations. Love the heat and Ice cream analogy..
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How the White House used studies with ‘weak’ evidence to tie Tylenol to autism
Experts say White House presented ‘association as causation’ and based conclusions on ‘poor quality studies’
https://www.theguardian.com/us-news/2025/oct/02/trump-tylenol-autism-expert-analysis?CMP=Share_iOSApp_Other
6 months ago
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This study, led by the talented grad student Boyang Li, identifies microglia undergoing cellular senescence in AD, and targeting cholesterol metabolism in senescent microglia is a therapeutic approach to slow AD progression.
onlinelibrary.wiley.com/doi/10.1111/...
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Microglial States Are Susceptible to Senescence and Cholesterol Dysregulation in Alzheimer's Disease
Senescent microglia in Alzheimer's disease exhibit dysregulated cholesterol metabolism and express Disease-Associated Microglia (DAM) signatures, including inflammatory and phagocytic markers. Single....
https://onlinelibrary.wiley.com/doi/10.1111/acel.70189
7 months ago
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news.uci.edu/2025/08/12/w...
Great work by a fantastic team!
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Women with Down syndrome may develop Alzheimer's disease more rapidly than men
UC Irvine study finds sex differences may impact treatment approaches
https://news.uci.edu/2025/08/12/women-with-down-syndrome-may-develop-alzheimers-disease-more-rapidly-than-men/
7 months ago
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reposted by
Hussein N. Yassine
Ian Kremer
7 months ago
Women with Down syndrome may develop Alzheimer's disease more rapidly than men
news.uci.edu/2025/08/12/w...
by
@ucirvine.bsky.social
#Alzheimers
#dementia
#DownSyndrome
#WomensHealth
@elizabethhead.bsky.social
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Women with Down syndrome may develop Alzheimer's disease more rapidly than men
UC Irvine study finds sex differences may impact treatment approaches
https://news.uci.edu/2025/08/12/women-with-down-syndrome-may-develop-alzheimers-disease-more-rapidly-than-men/
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SNAP program in vulnerable groups more effective in lowering cognitive decline than the more expensive intensive lifestyle intervention in the general population
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8 months ago
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reposted by
Hussein N. Yassine
National Alzheimer's Coordinating Center
8 months ago
Don't miss out on poster presentations by
#NIAfundedADRC
REC scholars today at
#AAIC2025
! Learn more about the Research, Education, Component (REC) and REC scholars:
naccdata.org/adrc-resourc...
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Congratulations to
@sdukehan.bsky.social
for leading a major gerontology journal
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8 months ago
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Fantastic work by a fantastic team!
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8 months ago
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Congratulations to Dobrin Nedelkov and Zoe Tsokolas! We demonstrate that apoE glycosylation in CSF predicts tau pathology in the ADNI cohort. We identify a new role for sugars attached to apoE in AD. Could less glycosylated apoE play a major role in tau spread?
link.springer.com/article/10.1...
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Increased cerebrospinal fluid and plasma apoE glycosylation is associated with reduced levels of Alzheimer’s disease biomarkers - Alzheimer's Research & Therapy
The apolipoprotein E (APOE) ε4 allele is the strongest genetic risk factor for late-onset Alzheimer’s disease (AD). ApoE is glycosylated with an O-linked Core-1 sialylated glycan at several sites; how...
https://link.springer.com/article/10.1186/s13195-025-01795-7?utm_source=rct_congratemailt&utm_medium=email&utm_campaign=oa_20250710&utm_content=10.1186/s13195-025-01795-7
8 months ago
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Is making brain HDL by inducing ABCA1 a viable strategy for APOE4 Alzheimer's? Our talented researcher Dr. Shaowei Wang has looked deeply into this question over the past 6 years, and the work has finally been published 1/4:
molecularneurodegeneration.biomedcentral.com/articles/10....
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Cellular senescence induced by cholesterol accumulation is mediated by lysosomal ABCA1 in APOE4 and AD - Molecular Neurodegeneration
Background Cellular senescence, a hallmark of aging, has been implicated in Alzheimer’s disease (AD) pathogenesis. Cholesterol accumulation is known to drive cellular senescence; however, its underlyi...
https://molecularneurodegeneration.biomedcentral.com/articles/10.1186/s13024-025-00802-7
about 1 year ago
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Our last publication for 2024. In a systematic review, we find little evidence for omega-3 polyunsaturated fatty acids (n-3 PUFA) supplementation on cognition in a general population:https://content.iospress.com/articles/journal-of-alzheimers-disease/jad231467
over 1 year ago
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How do brain lipids influence the development of cellular senescence in the brain? In this review, we propose over-activation of cPLA2 as a key driver of oxidized lipids and senescence and introduce the application of V-SYNTHES to develop potent cPLA2 inhibitors:
www.liebertpub.com/doi/pdf/10.1...
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Development of Calcium-Dependent Phospholipase A2 Inhibitors to Target Cellular Senescence and Oxidative Stress in Neurodegenerative Diseases | Antioxidants & Redox Signaling
Significance: Cellular senescence is a critical process underlying aging and is associated with age-related diseases such as Alzheimer’s disease. Lipids are implicated in cellular senescence. Fatty acids, particularly eicosanoids, have been associated with various forms of senescence and inflammation, and the associated reactive oxygen species production has been proposed as a therapeutic target for mitigating senescence. When overactivated, calcium-dependent phospholipase A2 (cPLA2) catalyzes the conversion of arachidonic acid into eicosanoids such as leukotrienes and prostaglandins. Recent Advances: With a growing understanding of the importance of lipids as mediators and modulators of senescence, cPLA2 has emerged as a compelling drug target. cPLA2 overactivation plays a significant role in several pathways associated with senescence, including neuroinflammation and oxidative stress. Critical Issues: Previous cPLA2 inhibitors have shown potential in ameliorating inflammation and oxidative stress, but the dominant hurdles in the central nervous system-targeting drug discovery are specificity and blood–brain barrier penetrance. Future Directions: With the need for more effective drugs against neurological diseases, we emphasize the significance of discovering new brain-penetrant, potent, and specific cPLA2 inhibitors. We discuss how the recently developed Virtual Synthon Hierarchical Enumeration Screening, an iterative synthon-based approach for fast structure-based virtual screening of billions of compounds, provides an efficient exploration of large chemical spaces for the discovery of brain-penetrant cPLA2 small-molecule inhibitors. Antioxid. Redox Signal. 00, 000–000.
https://www.liebertpub.com/doi/pdf/10.1089/ars.2024.0794
over 1 year ago
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