Aβ-degrading proteases:therapeutic potential in Alzheimer disease

The amyloid ß-protein (Aß) is well established to play an indispensible role in the pathogenesis of Alzheimer disease (AD). Aβ is subject to proteolytic degradation by a diverse array of peptidases and proteinases, known collectively as Aβ-degrading proteases (AβDPs). A growing number of AβDPs have been identified, which impact Aß powerfully and in a surprising variety of ways. As such, AßDPs hold considerable therapeutic potential for the treatment and/or prevention of AD. Here we critically review the relative merits of therapeutic strategies targeting AßDPs as compared to current Aß-lowering strategies focused on immunotherapies and pharmacological modulation of Aß-producing enzymes. Several innovative advances have increased considerably the feasibility of delivering AßDPs to the brain or enhancing their activity in a non-invasive manner. We argue that therapies targeting AßDPs offer numerous potential advantages, which should be explored through continued research into this promising field.