Specific Lipid Abnormalities Are Inherently Associated with Late-Onset Alzheimer's Disease

Introduction: Lipid abnormalities have been observed in brain, CSF, and blood in association with late-onset Alzheimer's disease (LOAD). It is unknown which abnormalities are precursors to LOAD and which are concomitants of illness or its treatment. Inherent abnormalities can be identified in induced pluripotent stem cell (iPSC)-derived neural lines. Methods: iPSC lines of patients with LOAD or healthy individuals were differentiated to astrocytes. Lipidomics analyses were performed on whole cell and mitochondrial extracts. Results: Large reductions in cholesterol esters (CE) and imbalances in fatty acids (FA) were observed in LOAD-associated cells or their mitochondria. There were only modest differences in other lipid classes, including membrane structural lipids. Discussion: The findings identify abnormalities in CE and FA as likely precursors to LOAD. These differences implicate mechanisms contributing to disease pathogenesis. Further study may lead to early interventions to prevent or delay LOAD.