Associations of ApoE4 status and DHA supplementation on plasma and CSF lipid profiles and entorhinal cortex thickness

Synthesis and Preclinical Evaluation of 22-[18F]Fluorodocosahexaenoic Acid as a Positron Emission Tomography Probe for Monitoring Brain Docosahexaenoic Acid Uptake Kinetics

“…Docosahexaenoic acid [22:6­( n -3), DHA] is the most abundant polyunsaturated fatty acid (PUFA) in the brain where it regulates several important processes and serves as a precursor to bioactive mediators to resolve inflammation in neurons, microglia, and endothelial cells. , However, the capacity of the brain to synthesize DHA locally is low, and the uptake of DHA from circulating lipid pools is arguably essential to maintaining homeostatic levels. ,− Brain DHA uptake and metabolism are affected by various factors that are implicated in the progression of neurodegenerative disorders such as Alzheimer’s disease (AD). , One factor that influences the metabolism and the production of bioactive lipid mediators in the brain is the apolipoprotein E4 (APOE4) allele, a major genetic risk factor for AD; APOE4 affects the catabolism, transport, and esterification of DHA in the brain, leading to changes in arachidonic acid (AA) and DHA signaling cascades across the lifespan. − These changes are associated with increased brain inflammation and amyloid deposition with APOE4 disrupting the associations of serum or plasma with brain DHA levels. − …”