Dr. Yassine is an Assistant Professor in the Department of Medicine, University of Southern California. The Yassine lab specializes in lipid metabolism, with an interest in Alzheimer's disease (AD).
Carrying the APOE e4 allele is the strongest genetic risk factors for developing AD. Although only 20% of humans are APOE e4 carriers, these individuals account for up to 65% of all AD cases.
Our research has been focused on the effect of APOE e4 on brain lipids in general and on the omega-3 fatty acid docosahexaenoic acid (DHA) in particular, and the mechanisms that regulate its brain delivery and metabolism.
We demonstrated that lower levels of serum DHA associated with greater amyloid deposition in cognitively healthy older adults (JAMA Neurology, 2016), but not in patients with dementia (Alzheimer’s Research & Therapy, 2016). In patients with dementia, we identified an association between APOE e4 genotype and reduced levels of cerebrospinal fluid DHA after supplementation (Alzheimer’s Research & Therapy 2016).
Using molecular studies, we identified that apoE apolipoproteins in cerebrospinal fluid have a decreased capacity to carry lipids by the ABCA-1 transporter, and that this lipid carrying capacity is lower in persons with mild cognitive impairment and Alzheimer’s compared to healthy controls (Journal of the American Heart Association, 2016).
Using PET scans, we reported an increased incorporation coefficient for brain DHA in APOE e4 suggesting a deficit in brain DHA delivery in younger healthy APOE e4 carriers decades before the onset of AD. (Alzheimer’s Research & Therapy 2017).
We hypothesize that apoE4 lipoproteins inefficiently transport lipids to brain areas involved in memory formation. Our long term goal is to demonstrate that AD pathology can be mitigated by enhancing apoE lipidation.
More information can be found at www.yassinelab.com
Department of Veterans Affairs VISN 18 Outstanding Research Award
Presidential Poster Award, Endocrine Society
Case Western Reserve University, Cleveland, OH : Resident Teacher of the Year Award, 2007
Beirut Arab University, Beirut, Lebanon : Dean's Honor List on graduation, 2003
Beirut Arab University, Beirut, Lebanon : Dean's Distinguished Student Medicine Day Award, 2002
DHA brain uptake and APOE4 status: a PET study with [1-11C]-DHA. Alzheimers Res Ther. 2017 Mar 23; 9(1):23. View in: PubMed
Association of Docosahexaenoic Acid Supplementation With Alzheimer Disease Stage in Apolipoprotein E e4 Carriers: A Review. JAMA Neurol. 2017 Jan 17. View in: PubMed
Changes in low-density lipoprotein size phenotypes associate with changes in apolipoprotein C-III glycoforms after dietary interventions. J Clin Lipidol. 2017 Jan - Feb; 11(1):224-233. e2. View in: PubMed
Association of Serum Docosahexaenoic Acid With Cerebral Amyloidosis. JAMA Neurol. 2016 Oct 1; 73(10):1208-1216. View in: PubMed
Development of quantitative mass spectrometric immunoassay for serum amyloid A. Biomarkers. 2016 Jul 22; 1-9. View in: PubMed
Posttranslational modifications of apolipoprotein A-II proteoforms in type 2 diabetes. J Clin Lipidol. 2016 Jul-Aug; 10(4):808-15. View in: PubMed
Disialylated apolipoprotein C-III proteoform is associated with improved lipids in prediabetes and type 2 diabetes. J Lipid Res. 2016 May; 57(5):894-905. View in: PubMed
The association of plasma cystatin C proteoforms with diabetic chronic kidney disease. Proteome Sci. 2016; 14:7. View in: PubMed
The effect of APOE genotype on the delivery of DHA to cerebrospinal fluid in Alzheimer's disease. Alzheimers Res Ther. 2016; 8:25. View in: PubMed
ABCA1-Mediated Cholesterol Efflux Capacity to Cerebrospinal Fluid Is Reduced in Patients With Mild Cognitive Impairment and Alzheimer's Disease. J Am Heart Assoc. 2016; 5(2). View in: PubMed
Site specific modification of the human plasma proteome by methylglyoxal. Toxicol Appl Pharmacol. 2015 Dec 1; 289(2):155-62. View in: PubMed
Serum amyloid a truncations in type 2 diabetes mellitus. PLoS One. 2015; 10(1):e0115320. View in: PubMed
The Association of Human Apolipoprotein C-III Sialylation Proteoforms with Plasma Triglycerides. PLoS One. 2015; 10(12):e0144138. View in: PubMed
The Application of Multiple Reaction Monitoring to Assess Apo A-I Methionine Oxidations in Diabetes and Cardiovascular Disease. Transl Proteom. 2014 Dec 1; 4-5:18-24. View in: PubMed
Elevated Plasma Albumin and Apolipoprotein A-I Oxidation under Suboptimal Specimen Storage Conditions. Mol Cell Proteomics. 2014 Jul; 13(7):1890-9. View in: PubMed
Enhanced cholesterol efflux to HDL through the ABCA1 transporter in hypertriglyceridemia of type 2 diabetes. Metabolism. 2014 May; 63(5):727-34. View in: PubMed
The application of multiple reaction monitoring and multi-analyte profiling to HDL proteins. Lipids Health Dis. 2014; 13(1):8. View in: PubMed
Mass spectrometric immunoassay and MRM as targeted MS-based quantitative approaches in biomarker development: potential applications to cardiovascular disease and diabetes. Proteomics Clin Appl. 2013 Aug; 7(7-8):528-40. View in: PubMed
Erlotinib-associated exacerbation of hypothyroidism with pericardial tamponade. Endocr Pract. 2012 Sep-Oct; 18(5):e111-3. View in: PubMed
Adjusting for Urinary Creatinine Overestimates Arsenic Concentrations in Diabetics. Cardiorenal Med. 2012 Feb; 2(1):26-32. View in: PubMed
New site(s) of methylglyoxal-modified human serum albumin, identified by multiple reaction monitoring, alter warfarin binding and prostaglandin metabolism. Chem Biol Interact. 2011 Jun 30; 192(1-2):122-8. View in: PubMed
Clinical determinants of aspirin resistance in diabetes. Diabetes Res Clin Pract. 2010 Oct; 90(1):e19-21. View in: PubMed
Effect of glucose or fat challenge on aspirin resistance in diabetes. Int J Endocrinol. 2010; 2010:820876. View in: PubMed
Effects of exercise and caloric restriction on insulin resistance and cardiometabolic risk factors in older obese adults--a randomized clinical trial. J Gerontol A Biol Sci Med Sci. 2009 Jan; 64(1):90-5. View in: PubMed