Cholesterol metabolic disturbance has been shown to promote the formation and deposition of beta-amyloid (Aβ) in Alzheimer's disease (AD). Several lines of evidences suggest the involvement of cholesterol-rich microdomains (lipid rafts) in the γ- and β-cleavage of the amyloid precursor protein (APP) and low cellular cholesterol levels or disruption of lipid rafts stimulates the non-pathogenic processing by α-secretase. Previous studies from our laboratory have revealed that cholesterol, besides enhancing Aβ production, increases the susceptibility to Aβ-induced oxidative stress, by modulating the mitochondrial pool of glutathione (mGSH), a major defence against ROS generated from mitochondria.Thus, the aim of this work was to examine in vivo the correlation between elevated levels of brain mitochondrial cholesterol and the severity of AD-like neuroinflammation and neuronal damage.

Comunicación presentada en la Alzheimer's Association International Conference on Alzheimer's Disease, celebrada del 26 al 31 de julio de 2008 en Chicago (Estados Unidos)

Peer Reviewed