Synonyms: (Amyloid Precursor Protein), amyloid beta (A4) precursor protein


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The amyloid precursor protein (APP) is central to the study of Alzheimer’s disease. Abundant in neurons, APP is a type I transmembrane protein whose proteolysis gives rise to amyloid-β (Aβ) peptides. Rare mutations in APP cause familial Alzheimer’s disease. The majority of pathogenic APP mutations cluster near the cleavage sites of the proteases β-secretase and γ-secretase, and generally increase total Aβ levels and/or the Aβ42/Aβ40 ratio. APP promoter mutations and APP gene duplication have the same effect. Other mutations in APP are associated with rare cases of familial cerebral amyloid angiopathy (CAA). A protective APP mutation reduces lifetime Aβ generation by 20 percent. In addition, several known genetic risk factors for late-onset AD, including APOE, ABCA7, BIN1, CD33, clusterin, PICALM, and SORLA, are thought to modulate APP biology, with effects on APP processing, trafficking, and clearance.

APP interacts with cell-surface proteins, though whether it is primarily a ligand or receptor is unclear. Its extracellular cleavage product sAPPα is neurotrophic; its cleaved intracellular domain AICD has been reported to regulate gene expression, but no target genes have been broadly confirmed. Aside from its role in Aβ generation, various functions have been ascribed to the APP protein. During brain development, these include neuronal and synaptic adhesion, formation of the neuromuscular junction, and cell signaling. In the adult brain, response to neuronal damage has been suggested as an important APP function. APP knockout mice are viable and show subtle phenotypes; when the APP gene family member APLP2 is deleted as well, double knockout mice die at birth. Despite extensive research, the primary physiological function of APP remains an enigma.


Alzpedia Citations

  1. Amyloid-β (Aβ)
  2. APOE
  3. ABCA7
  4. Bridging integrator 1 (BIN1)
  5. CD33
  6. Clusterin
  8. SORLA (SORL1)

Further Reading


  1. . Trafficking and Proteolytic Processing of APP. Cold Spring Harb Perspect Med. 2012 May;2(5):a006270. PubMed.
  2. . Physiological Functions of APP Family Proteins. Cold Spring Harb Perspect Med. 2012 Feb;2(2):a006288. PubMed.
  3. . Amyloid precursor protein processing and Alzheimer's disease. Annu Rev Neurosci. 2011;34:185-204. PubMed.
  4. . The amyloid precursor protein intracellular domain (AICD) as modulator of gene expression, apoptosis, and cytoskeletal dynamics-relevance for Alzheimer's disease. Prog Neurobiol. 2008 Aug;85(4):393-406. PubMed.