THE IMPACT OF ALTERED LIPID METABOLISM ON APOE-DEPENDENT ALZHEIMER’S DISEASE PATHOLOGY
Author
Doskicz, Hannah RoseIssue Date
2022Keywords
Alzheimer’s disease (AD)apolipoprotein E (APOE)
arachidonic acid (ARA)
fatty acid desaturase (FADS)
lysolipids (LP)
omega-3 (n-3)
omega-6 (n-6)
phospholipids (PL)
lyso-phosphatidylcholine (LPC)
lyso-phosphatidylethanolamine (LPE)
lyso-phosphatidylserine (LPS)
Advisor
Chilton, Floyd
Metadata
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The University of Arizona.Rights
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.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.Type
Electronic Thesistext
Degree Name
B.S.Degree Level
bachelorsDegree Program
PhysiologyHonors College