Regulation of Amyloid β-Protein Precursor Processing by Cell Surface Receptor Ligands and Second Messengers

Deposition of brain amyloid plaques is an early and invariant neuropathological feature of Alzheimer’s disease (AD). Up to 5%–20% of the brain cortex volume can be filled with amyloid in some forms of the disease (Hyman et al. 1995). Brain amyloid plaques are composed of insoluble aggregates of amyloid β peptide (Aβ) that is derived from proteolytic processing of the larger amyloid precursor protein (APP). APP is a member of a gene family that encodes ubiquitously expressed secretory glycoproteins (Kang et al. 1987; Slunt et al. 1994; Wasco et al. 1993; Weidemann et al. 1989) with yet unidentified functions related to cell adhesion, axogenesis, neurite outgrowth and neuroprotection (Barger et al. 1995; Milward et al. 1992; Ninomiya et al. 1995; Thinakaran et al. 1995; Williamson et al. 1995).