Proteolytic degradation of the amyloid β-protein: The forgotten side of Alzheimer's disease

Proteases have long played a central role in the molecular pathogenesis of Alzheimer's disease (AD), yet proteases that degrade the amyloid β-protein (Aβ) itself were largely ignored until only quite recently. Today, we know that Aβ-degrading proteases are critical regulators of brain Aβ levels in vivo, with evidence accumulating that their dysfunction may play a role in the etiology of AD. This review explores the historical factors that obscured this important aspect of amyloidogenesis, and discusses the many fresh insights it offers into the causes of and potential treatments for AD.