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