Keck School Faculty

Hussein Yassine, MD
Hussein Yassine, MD
Associate Professor of Medicine
CSC 210 Health Sciences Campus Los Angeles
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

: Presidential Poster Award, Endocrine Society , 2009

: Department of Veterans Affairs VISN 18 Outstanding Research Award , 2009

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

Simple and Fast Assay for Apolipoprotein E Phenotyping and Glycotyping: Discovering Isoform-Specific Glycosylation in Plasma and Cerebrospinal Fluid J Alzheimers Dis. 2020 Jun 17. . View in PubMed

Do menopausal status and APOE4 genotype alter the long-term effects of intensive lifestyle intervention on cognitive function in women with type 2 diabetes mellitus? Neurobiol Aging. 2020 Apr 08; 92:61-72.. View in PubMed

Sex-Related Differences in Brain Volumes and Cerebral Blood Flow Among Overweight and Obese Adults With Type 2 Diabetes: Exploratory Analyses From the Action for Health in Diabetes Brain Magnetic Resonance Imaging Study J Gerontol A Biol Sci Med Sci. 2020 Mar 09; 75(4):771-778. . View in PubMed

Effect of APOE Genotype on Plasma Docosahexaenoic Acid (DHA), Eicosapentaenoic Acid, Arachidonic Acid, and Hippocampal Volume in the Alzheimer's Disease Cooperative Study-Sponsored DHA Clinical Trial J Alzheimers Dis. 2020; 74(3):975-990. . View in PubMed

APOE Alleles and Diet in Brain Aging and Alzheimer's Disease Front Aging Neurosci. 2020; 12:150. . View in PubMed

ApoC-III Glycoforms Are Differentially Cleared by Hepatic TRL (Triglyceride-Rich Lipoprotein) Receptors Arterioscler Thromb Vasc Biol. 2019 10; 39(10):2145-2156. . View in PubMed

Low-Density Lipoprotein Particle Size Subfractions and Cerebral Amyloidosis J Alzheimers Dis. 2019; 68(3):983-990. . View in PubMed

ApoE4 Alters ABCA1 Membrane Trafficking in Astrocytes J Neurosci. 2019 11 27; 39(48):9611-9622. . View in PubMed

Development of a delayed-release nutrient for appetite control in adults with obesity and type 2 diabetes and initial clinical testing in a single dose randomized controlled trial Nutr Diabetes. 2019 07 15; 9(1):20. . View in PubMed

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 Mar 01; 74(3):339-347. . View in PubMed

Targeting prodromal Alzheimer's disease: too late for prevention? Lancet Neurol. 2017 12; 16(12):946-947.. View in PubMed

Lessons from the Multidomain Alzheimer Preventive Trial Lancet Neurol. 2017 08; 16(8):585-586. . View in PubMed

Ex vivo instability of glycated albumin: A role for autoxidative glycation Arch Biochem Biophys. 2017 09 01; 629:36-42. . View in PubMed

Changes in low-density lipoprotein size phenotypes associate with changes in apolipoprotein C-III glycoforms after dietary interventionsJ Clin Lipidol. 2017 Jan - Feb; 11(1):224-233. e2. . View in PubMed

Development of quantitative mass spectrometric immunoassay for serum amyloid A Biomarkers. 2016 Dec; 21(8):743-751. . View in PubMed

Association of Serum Docosahexaenoic Acid With Cerebral Amyloidosis JAMA Neurol. 2016 Oct 01; 73(10):1208-1216. . View in PubMed

Posttranslational modifications of apolipoprotein A-II proteoforms in type 2 diabetes J Clin Lipidol. 2016 Jul-Aug; 10(4):808-815. . 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 Feb 12; 5(2). . View in PubMed

Disialylated apolipoprotein C-III proteoform is associated with improved lipids in prediabetes and type 2 diabetes J Lipid Res. 2016 05; 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 06 30; 8:25. . View in PubMed

Site specific modification of the human plasma proteome by methylglyoxal Toxicol Appl Pharmacol. 2015 Dec 01; 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 01; 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 Jan 08; 13:8. . 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

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