DHA brain uptake and APOE4 status: a PET study with [1-11C]-DHA.
BACKGROUND
The apolipoprotein E ɛ4 (APOE4) allele is the strongest genetic risk factor identified for developing Alzheimer's disease (AD). Among brain lipids, alteration in the ω-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) homeostasis is implicated in AD pathogenesis. APOE4 may influence both brain DHA metabolism and cognitive outcomes.


METHODS
Using positron emission tomography, regional incorporation coefficients (k*), rates of DHA incorporation from plasma into the brain using [1-11C]-DHA (Jin), and regional cerebral blood flow using [15O]-water were measured in 22 middle-aged healthy adults (mean age 35 years, range 19-65 years). Data were partially volume error-corrected for brain atrophy. APOE4 phenotype was determined by protein expression, and unesterified DHA concentrations were quantified in plasma. An exploratory post hoc analysis of the effect of APOE4 on DHA brain kinetics was performed.


RESULTS
The mean global gray matter DHA incorporation coefficient, k*, was significantly higher (16%) among APOE4 carriers (n = 9) than among noncarriers (n = 13, p = 0.046). Higher DHA incorporation coefficients were observed in several brain regions, particularly in the entorhinal subregion, an area affected early in AD pathogenesis. Cerebral blood flow, unesterified plasma DHA, and whole brain DHA incorporation rate (Jin) did not differ significantly between the APOE groups.


CONCLUSIONS
Our findings suggest an increase in the DHA incorporation coefficient in several brain regions in APOE4 carriers. These findings may contribute to understanding how APOE4 genotypes affect AD risk.
Department of Medicine, University of Southern California, 2250 Alcazar Street, Room 210, Los Angeles, CA, 90033, USA. hyassine@usc.edu.
Hussein N
HN
Yassine
Research Center on Aging, University of Sherbrooke, Sherbrooke, QC, Canada.
Etienne
E
Croteau
Department of Medicine, University of Southern California, 2250 Alcazar Street, Room 210, Los Angeles, CA, 90033, USA.
Varun
V
Rawat
Section on Nutritional Neurosciences, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD, USA.
Joseph R
JR
Hibbeln
Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
Stanley I
SI
Rapoport
Research Center on Aging, University of Sherbrooke, Sherbrooke, QC, Canada.
Stephen C
SC
Cunnane
Section on Nutritional Neurosciences, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD, USA.|Division of Psychiatry Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, College Park, MD, USA.
John C
JC
Umhau
D000328:Adult; D000368:Aged; D053327:Apolipoprotein E4 / Q000378:metabolism*; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D004281:Docosahexaenoic Acids / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D057054:Molecular Imaging / Q000379:methods; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D012016:Reference Values; D014018:Tissue Distribution
D053327:Apolipoprotein E4; D002250:Carbon Radioisotopes; D019275:Radiopharmaceuticals; D004281:Docosahexaenoic Acids
APOE; Alzheimer’s disease; DHA; PET