Amyloid Precursor protein and neuronal degeneration in Alzheimer´s disease.

LORENZO ALFREDO; HEREDIA FLORENCIA; BIGNANTE ANAHÍ; GHIBAUDO FLORENCIA; HELGUERA PABLO

Simposio; 2º Simposio Franco-Argentino de Neurociencias; 2012

Amyloid beta (Aβ) is a metabolic product of Amyloid β Precursor protein (APP).  Deposition of Aβ in the brain and neuronal degeneration are characteristic hallmarks of Alzheimer’s disease (AD).  Aβ induces neuronal degeneration, but the mechanism of neurotoxicity remains elusive.  In this presentation, we will show cellular and molecular evidence for the involvement of APP in the mechanism of neuronal degeneration elicited by Aβ.  By overexpressing different mutant forms of APP into primary hippocampal neurons in vitro we show that Aβ interacts with APP and triggers a Go-dependent signaling cascade that promotes neuronal death.  Importantly, we will also present novel evidence indicating that the recently discovered mutation in APP intracellular domain (APPH733P) confers resistance to Aβ-induced neurodegeneration suggesting that it might reduce the risk of AD on its carriers.Our data suggest that APP plays a critical role in neuronal disfunction in AD beyond its well established participation as the only source of Aβ. Grant support: CONICET and ANPCyT (PICT2010-1895) to AL