Assistant Professor, Medicine - Endocrinology
Research OverviewThe Yassine Lab seeks to address the contributions of lipid metabolism to Alzheimer's disease (AD) pathology. Specifically, his laboratory's work has focused on understanding how APOE4 lipid metabolism contributes to AD.
The gene APOE4 is a strong risk factor for AD. One of every five people in the population carries the gene, as do more than half of patients with AD. Yet, how APOE4 is involved in AD remains a mystery. Clues to this mystery may lie in understanding the basic biology of the protein that is produced from APOE4. That protein normally carries important lipids such as omega-3-fatty acids (part of fish oil nutrient supplements) from the bloodstream to the brain. In the brain these fatty acids are critical for memory functions.
The Yassine Lab reported an inverse association between serum DHA levels and brain amyloidosis, memory functions and hippocampal volume in older persons without dementia. This association was not observed in patients with Alzheimer's disease, indicating the importance of DHA in early disease stages but not late in the disease process. In 2016, Dr. Yassine and his team reported that in patients with mild AD and carrying the APOE4 gene, DHA supplementation led to lower CSF DHA levels compared with those not carrying the APOE4 allele.
The Yassine lab is now studying whether cognitively normal APOE4 carriers have inefficient omega-3 fatty acid metabolism in the brain decades before they develop AD. Dr. Yassine and his team revealed that cognitively normal APOE4 carriers had an increase in brain DHA uptake. This indicated a brain DHA deficit in APOE4 carriers at a young age that could be mitigated with DHA supplementation. Dr. Yassine is now leading a randomized controlled clinical trial to understand whether omega-3 supplementation may help prevent or delay AD in people who carry the APOE4 allele.
To understand the mechanisms linking APOE4 with lipid metabolism, Dr. Yassine is studying how DHA is transported by APOE lipoproteins using elegant in vivo and in vitro models. The Yassine lab demonstrated that APOE4 lipoproteins have decreased affinity to acquire lipids by the ABCA-1 transporter. This defect was rescued by inducing ABCA-1 activity. This opens the therapeutic avenue of activating the ABCA-1 transporter in order to facilitate brain DHA transport. Dr. Yassine is utilizing ABCA-1 agonists to restore APOE lipidation, and provide a mechanism to offset AD risk in APOE4 carriers.
Office Location CSC 210
Office Phone (216) 526-6316
Fax (323) 442-2082
Office Location CSC 210
- 09/97-06/2003 MD, Beirut Arab University
- 06/04-06/07 Case Western Reserve University
- 07/07-06/10 University of Arizona
Selected PublicationsView a complete PubMed search
- Yassine, HN., Croteau, E., Rawat, V., Hibbeln, J. R., Rapoport, S. I., Cunnane, S. C., & Umhau, J. C. DHA brain uptake and APOE4 status: A PET study with [1-11C]-DHA. Alzheimer's research & therapy, 2017:9(1), 23. PMCID: PMC5364667
- Yassine HN, Braskie MN, Mack WJ, Castor KJ, Fonteh AN, Schneider LS, Harrington MG, Chui, HC Literature-Based Association of Docosahexaenoic acid Supplementation with Alzheimerâs Disease Stage in Apolipoprotein E É4 carriers. JAMA Neurol. January 17, 2017. doi:10.1001/jamaneurol.2016.4899
- Yassine HN, Feng Q, Azizkhanian I, Rawat V, Castor K, Fonteh A, Harrington MG, Zheng L, Reed BR, DeCarli C, Jagust WJ, Chui, HC. The Association of Serum Docosahexaenoic Acid with Cerebral Amyloidosis. JAMA Neurol. 2016 Aug 8. doi: 10.1001/jamaneurol.2016.1924., PMID: 27532692.
- Yassine HN; Rawat V; Mack WJ; Quinn JF; Yurko-Mauro K; Bailey-Hall E; Aisen PS;. Chui HC; Schneider LS. The effect of APOE genotype on the delivery of DHA to cerebrospinal fluid in Alzheimer's disease. Alzheimer's Research & Therapy. 2016;8:1-10. PMCID: PMC4928349
- Yassine HN, Feng Q, Chiang J, Petrosspour LM, Fonteh NA, Chui HC, Harrington MG, ABCA-1 mediated cholesterol efflux capacity to cerebrospinal fluid is reduced in patients with mild cognitive impairment and Alzheimerâs disease. Journal of the American Heart Association. 2016. 5(2): p. e002886. PMID: 26873692