What can lipidomics tell us about the pathogenesis of Alzheimer disease?

Abstract

Lipids serve many distinct functions in cellular homeostasis such as membrane organization, as a platform for membrane function and protein/protein or protein/lipid interaction, energy storage, as well as secondary messengers in signal transduction. Perturbations in lipid homeostasis may result in abnormal cellular function. Alzheimer's disease (AD) is a neurodegenerative disorder in which the brain represents the primary site of pathology. While there is a plethora of previous work pertaining to AD pathogenesis, the precise mechanism of the disease is still not well-understood. Recent waves of technological advances in the realm of lipidomics have enabled scientists to look at AD pathogenesis from a previously unexplored perspective, and studies have revealed extensive lipid aberrations are implicated in the disease pathology. Herein, we review the critical lipids alternations, which affect amyloid plaque and neurofibrillary tangles formation and accumulation, as well as lipid aberrations related to neuronal and synaptic dysfunction in cells and animal models. We also summarize lipid abnormalities observed in the human cerebrospinal fluid (CSF), as well as other circulating fluids including plasma and serum in association with AD, which could serve as candidate biomarkers to diagnose and monitor the disease.