APP signaling in Alzheimer{s disease

BIGNANTE, ELENA A.; ALFREDO LORENZO

Aging

Impact journals

Lugar: Albany; Año: 2018

1945-4589

large body of evidence supports the Amyloid β (Aβ) cascade hypothesis underlying neurodegeneration in Alzheimer?s disease (AD). Although the mechanism by which Aβ induces neuronal dysfunction and death is still matter of debate, in the last two decades several groups have generated compelling evidence supporting a role of Amyloid β Precursor Protein (APP) as a bona fide receptor for Aβ that can trigger neurodegeneration (1). Our initial discovery that APP binds Aβ fibrils and mediates its neurotoxic effect on neuronal cultures (2) was subsequently extended by reports showing that harmful effects of diverse Aβ-assemblies are APP-dependent. Recently, Wang and collaborators reported that both, Aβ-derived diffusible ligands (ADDL) and Aβ oligomers extracted from human AD brain, impaired long-term potentiation in an APP-dependent manner (3). Furthermore, another group showed that intracranial infusion of Aβ oligomers impaired associative