Cholesterol and ApoE in Alzheimer’s disease

Abstract

Genetic, neuropathological and biochemical studies suggest strong links between cholesterol, the apolipoprotein E (APOE) and Alzheimer’s disease (AD), both in humans and in animal models of the disease. From the literature and our work, we can predict that transient increase of the levels of cholesterol at the membrane of neurons would profoundly affect the processing of the transmembrane Amyloid Precursor Protein (APP) by triggering its clathrin dependent endocytosis and the resulting production of amyloid-β (Aβ) peptides. Here, we will review these data together with structural and molecular dynamic studies that characterized the role of cholesterol on APP conformation and positioning at the membrane. Specifically decreasing brain cholesterol or replacing it with plant sterols crossing the blood brain barrier appear like promising strategies to either delay or counteract the development of sporadic AD.

ApoE Lipidation as a Therapeutic Target in Alzheimer’s Disease

“…Cholesterol is one of the major components of cellular membranes and acts to make membranes more fluid and to decrease membrane permeability to hydrophilic molecules [ 98 ]. Importantly, cholesterol is rich in lipid rafts which are essential domains involved in signal transduction, neuronal cell adhesion, axon guidance and synaptic transmission.…”

Les lipides dans la maladie d’Alzheimer

“…Marie-Claude Potier, Linda Hanbouch et Catherine Marquer (Institut du cerveau et de la moelle épinière, hôpital de la Pitié-Salpêtrière, Paris, France) passent en revue les preuves suggérant que l'augmentation transitoire des niveaux de cholestérol de la membrane des neurones affectera profondément le positionnement transmembranaire de la protéine précurseur amyloïde et son traitement, entraînant une surproduction de peptides amyloïdes-b (Potier et al, 2018).…”