Study of the mechanism of enrichment of APP in endosomes induced by Aβ and its modulation by Gβγ signaling

ANTONINO, MAGDALENA; MARMO, PAULA; ALFREDO, LORENZO; BIGNANTE, ELENA ANAHI

Buenos Aires

Congreso; XXXVII SAN Annual Congress; 2022

Sociedad Argentina de Neurociencia

Alzheimer´s disease is characterized by the deposition of aggregated species of amyloid beta (Aβ) in the brain, which leads to progressive cognitive deficits and dementia. We recently found that Aβ assemblies, oligomers and fibrils (o-Aβ and f-Aβ), increase APP and BACE1 interaction in recycling endosomes of human neurons derived from iPSCs by a mechanism dependent of APP/Go/Gβγ signaling. Now, we are interested on deepen in the APP trafficking in the endo lysosomal pathway in order to understand the mechanism underlying such effect. We found that Aβ induced an enrichment of APP in recycling endosomes at the expense of a decrement of its levels in lysosomes. This change in APP intracellular distribution is drive by Gβγ signaling, since is avoided by the pharmacologically inhibitor gallein. Moreover, we found that the changes on APP distribution correlatewith an increase in its interaction with BACE1, also modulates by a Gβγ signaling.