24(S)hydroxycholesterol as predisposing agent for Alzheimer’s disease

CATALDI, GABRIEL G.; MAURICIO G MARTÍN

Congreso; Encuentro de la Sociedad Argentina de Neurociencias 2022; 2022

CYP46 carries out the hydroxylation of cholesterol to 24(S)HOC, which is the mainmechanism of cholesterol elimination from the brain. CYP46 has been mainly reported inneuronal populations, however, in cases of brain damage such as traumatic brain injury orAlzheimer’s disease CYP46 increases its expression in astrocytes. However, the role thatCYP46 would play in astrocytes in pathological conditions is unknown.We found that CYP46 levels are greatly increased in reactive astrocytes treated withlipopolysaccharide (LPS) and IL-6. Accordingly, IL-6 was able to increase APP synthesis inprimary astrocytes. Providing a link between CYP46 and APP, our results show that24(S)HOC-treated primary cortical astrocytes showed a marked increase in APP levelscompared to control cells. Our data indicate that 24(S)HOC appears to exert its role throughepigenetic mechanisms.We propose that under a proinflammatrory context, as for example a microbial infection inthe brain, 24(S)HOC would mediate the production of APP and Abeta in astrocytes to face theaggression but on the other side it would predispose to Alzheimer's disease.