Therapeutic targeting of the alpha-secretase pathway to treat Alzheimer's disease.

Alzheimer's disease (AD) is a progressive and degenerative disorder pathophysiologically characterized by the accumulation of beta-amyloid peptides (A-beta) in the brain. A-beta is indicated to be the primary agent in the pathogenesis of AD. A-beta is generated from the amyloid precursor protein (APP) via two proteolytic enzymes, beta- and gamma-secretases. Alpha-secretase conducts an alternative proteolytic cleavage that prevents A-beta production and accumulation. Elevating levels of alpha-secretase cleavage, therefore, is a potential therapeutic strategy to treat AD.