THE IMPACT OF ALTERED LIPID METABOLISM ON APOE-DEPENDENT ALZHEIMER’S DISEASE PATHOLOGY

Abstract

Alzheimer’s disease (AD) is a devastating condition with a largely unknown etiology and no known cure. AD is associated with an aberrant lipid metabolism; alterations in phospholipids, polyunsaturated fatty acids, and cholesterol have been well documented. The present study examined the potential role of genetic variation in the FADS gene and altered lipid metabolism seen in AD. Single nucleotide polymorphisms (SNPs) in the FADS gene cluster affect long chain polyunsaturated fatty acid (LC-PUFA) biosynthesis leading to numerous downstream metabolic changes. One hundred and seventy-four frontal cortex tissue samples from non-AD and AD subjects were genotyped for APOE status and the FADS SNP rs174537. Additionally, lipids were extracted to determine levels of lyso-phospholipids and total fatty acids using targeted lipidomics and GC-FID, respectively. No significant associations between AD, APOE status, and FADS genotype were observed (P > .05); however, Chi-square analysis suggested a potential association with the “ancestral” T allele. Targeted lipidomics revealed significant changes (P < .05) in several molecular species of lyso-phosphatidylcholines, lyso-phosphatidylethanolamines, and lyso-phosphatidylserines. Additionally, measurements of total fatty acid levels in healthy frontal cortex tissue indicate that C18:1 n-9 oleic acid-cis, C18:0 stearic acid, C16:0 palmitic acid, C20:4 ARA (n-6), C22:4 adrenic acid (n-6), and C22:6 DHA (n-3) were the primary fatty acids in this brain region. Our preliminary findings may suggest that individualistic nutritional recommendations could mitigate AD risk.