Abstract
Perturbation of the homeostasis of brain membrane lipids has been implicated in the pathomechanism of Alzheimer's disease (AD). The ε4 allele of the apolipoprotein E gene (APOE) confers an increased risk, in a dosage-dependent manner, for brain amyloid-β accumulation and the development of sporadic AD. An effect of the APOE genotype on brain lipid homeostasis may underlie the AD risk associated with the ε4 allele. In this research, we examined an effect of APOE ε4 on the lipid class composition of crude membranes and raft-enriched fractions of brains. We applied enzymatic reaction-based methods for the quantification of phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidic acid, and sphingomyelin. Our results indicate that brain lipid class composition was neither significantly altered in AD subjects nor affected by the presence of the APOE ε4 allele.
Highlights
Alzheimer’s disease (AD) is a polygenic neurodegenerative disease characterized clinically by progressive memory loss and, eventually, dementia
The cores of the senile plaques are composed of aggregated amyloid-β (Aβ) peptide, which is generated from a neuronal transmembrane protein called amyloid precursor protein (APP), and trigger AD pathogenesis
All 20 of the brains from individuals diagnosed with AD were observed to have a combination of neurofibrillary change of stage IV or above and senile plaque stage C (Table 1), which meet the criteria for definitive diagnosis of AD [21]
Summary
Alzheimer’s disease (AD) is a polygenic neurodegenerative disease characterized clinically by progressive memory loss and, eventually, dementia. The genetic heritability of the sporadic form has been estimated to be 60%–80% [1,2]. The brains of AD patients exhibit loss of synapses and neurons, as well as the presence of neuropathological hallmarks such as senile plaques and neurofibrillary changes. Altered metabolism of brain membrane lipids has been implicated in the pathogenesis of AD. This hypothesis is based upon multiple lines of evidence. The apolipoprotein E (apoE)-encoding gene (APOE) is the strongest genetic risk factor for a sporadic form of AD. Genetic loci close to the ABCA7, TREM2, and SORL1 genes, which may be implicated in lipid metabolism, have been shown to be associated with sporadic AD [4]. The pathogenic potency of Aβ species depends on the length of the
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