Developing Topics.

Background: Aβ accumulation is a key event driving neurotoxicity in Alzheimer's disease. Previously, we demonstrated that oligomers of amyloid beta (oAβ) induce an increase in the levels of APP and BACE1 in Rab11-positive endosomes, leading to the intracellular accumulation of Aβ1-42 in human neurons derived from iPSCs (HN-iPSCs). This vicious cycle of Aβ generation induced by Aβ itself, is pivotal for the propagation of pathology.

Aβ Assemblies Promote Amyloidogenic Processing of APP and Intracellular Accumulation of Aβ42 Through Go/Gβγ Signaling.

Alzheimer's disease (AD) is characterized by the deposition of aggregated species of amyloid beta (Aβ) in the brain, which leads to progressive cognitive deficits and dementia. Aβ is generated by the successive cleavage of the amyloid precursor protein (APP), first by β-site APP cleaving enzyme 1 (BACE1) and subsequently by the γ-secretase complex. Those conditions which enhace or reduce its clearance predispose to Aβ aggregation and the development of AD.