Beyond pathology: APP, brain development and Alzheimer's disease

•Abeta peptide biology rather than APP biology has been the main focus of AD field in the past 20 years.•The amyloid cascade hypothesis failed to produce effective AD therapeutics.•A deeper understanding of AD development needs better insight into the biological function of APP.•APP is involved in brain development and wiring by affecting cytoskeleton modification and rearrangement.•A characterization of the molecular mechanisms underlying APP function is needed to clarify its role in AD.

Alzheimer's disease (AD) is the most common form of dementia among the elderly. Research in the AD field has been mostly focused on the biology of the Aβ peptide but increasing evidence is shifting attention toward the physiological role of APP as key to understanding AD pathology. It is becoming apparent that APP plays a central role in the mechanisms that guarantee the accuracy and the robustness of brain wiring. In the present review we explore APP functions with focus on some of the underlying molecular mechanisms.