η-Secretase: Reduction of Amyloid Precursor Protein η-Site Cleavage in Alzheimer's Disease

The accumulation and deposition of fibrillar Aβ is thought the primary cause of Alzheimer's disease (AD). Aβ is generated by sequential proteolytic processing involving β- and γ-secretase on Amyloid β protein precursor (APP). Recently, γ-secretase was shown to cleave near the cytoplasmic membrane boundary of APP, called η-site cleavage, as well as in the middle of the membrane domain, called γ-site cleavage. Recent findings indicate that γ- and η-site cleavage are regulated independently. In this review, the reduction of η-site cleavage in AD and the importance of η-site cleavage are discussed.