The Yassine team is a multidisciplinary group that combines expertise in lipid metabolism and genetics with imaging and clinical trial infrastructure. Our goal is to expand the role of ApoE4 in lipid metabolism relevant to Alzheimer’s disease (AD).
The first focus of our lab is in investigating how ApoE interacts with ABCA1 to form an HDL particle in the brain. We identified that the function of the cholesterol transporter ABCA1 was lower in patients with AD in CSF compared with persons who are not cognitively impaired (J Am Heart Assoc, 2016). We are investigating the interactions of ABCA1 with ApoE proteins, in addition to detailed characterizations of brain and plasma HDL particles (Project 1).
The second focus of our lab is on investigating how ApoE4 affects DHA transport to the brain. We found a strong relationship of lower serum DHA to greater amyloid deposition in cognitively healthy older adults (JAMA Neurology, 2016). Then, using [11C]-DHA PET, we showed that brains of young cognitively healthy APOE4 carriers had more uptake of plasma DHA (Alzheimer’s Research & Therapy, 2017). These data indicate that cognitively normal ApoE4 carriers have deficits of DHA before the onset of AD and may be more vulnerable to dietary DHA deficiency. These findings suggested a role for DHA supplementation in the prevention (JAMA Neurology 2017). A pilot study (Alzheimer’s Association, NIRG-15-361854) showed that APOE genotype altered CSF DHA levels after supplementation. These findings enabled us to obtain NIA funding for a double-blind placebo-controlled clinical trial of DHA in healthy elderly stratified by APOE status (Project 2 and Project 3).