Amyloid precursor protein (APP)

Protein involved in Alzheimer's disease

General Information

Alzheimer's disease is characterized by the accumulation of β-amyloid peptides in plaques and vessel walls and by the intraneuronal accumulation of paired helical filaments composed of hyperphosphorylated tau.
Amyloid precursor protein APP is part of a super-family of transmembrane and secreted proteins. It appears to have a number of roles, including regulation of haemostasis and mediation of neuroprotection. APP also has metal and heparin-binding properties. Cleavage of amyloid precursor protein by β- and γ-secretases results in the generation of the Aβ (βA4)peptide, whereas α-secretase cleaves within the Aβ sequence and prevents formation from APP.
Recent findings indicate that the site of γ-secretase cleavage is critical to the development of amyloid deposits. Aβ1-42 is much more amyloidogenic than Aβ1-40. Aβ1-42 formation is favoured by mutations in the two presenilin genes (PS1 and PS2), and by the commonest amyloid precursor protein mutations.