The APP family of proteins: similarities and differences

Overwhelming evidence indicates that the Aβ (amyloid β-peptide) plays a critical role in the pathogenesis of Alzheimer's disease. Aβ is derived from the APP (amyloid precursor protein) by the action of two aspartyl proteases (β- and γ-secretases) that are leading candidates for therapeutic intervention. APP is a member of a multigene family that includes APLP1 (amyloid precursor-like protein 1) and APLP2. Both APLPs are processed in a manner analogous to APP, with all three proteins subject to ectodomain shedding and subsequent cleavage by γ-secretase. Careful study of the APP family of proteins has already revealed important insights about APP. Here, we will review how knowledge of the similarities and differences between APP and the APLPs may prove useful for the development of novel disease-modifying therapeutics.