A New Hypothesis for Alzheimer's Disease: The Lipid Invasion Model.

ABSTRACT: This paper proposes a new hypothesis for Alzheimer's disease (AD)-the lipid invasion model. It argues that AD results from external influx of free fatty acids (FFAs) and lipid-rich lipoproteins into the brain, following disruption of the blood-brain barrier (BBB). The lipid invasion model explains how the influx of albumin-bound FFAs via a disrupted BBB induces bioenergetic changes and oxidative stress, stimulates microglia-driven neuroinflammation, and causes anterograde amnesia. It also explains how the influx of external lipoproteins, which are much larger and more lipid-rich, especially more cholesterol-rich, than those normally present in the brain, causes endosomal-lysosomal abnormalities and overproduction of the peptide amyloid-β (Aβ). This leads to the formation of amyloid plaques

SUBMITTER: Rudge JD 

PROVIDER: S-EPMC9028744 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature