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APP

Reviewed December 2008

What is the official name of the APP gene?

The official name of this gene is “amyloid beta (A4) precursor protein.”

APP is the gene's official symbol. The APP gene is also known by other names, listed below.

What is the normal function of the APP gene?

The APP gene provides instructions for making a protein called amyloid precursor protein. This protein is found in many tissues and organs, including the brain and spinal cord (central nervous system). Little is known about the function of amyloid precursor protein. Researchers speculate that it may bind to other proteins on the surface of cells or help cells attach to one another.

Amyloid precursor protein is cut by enzymes to create smaller fragments (peptides), some of which are released outside the cell. Two of these fragments are called soluble amyloid precursor protein (sAPP) and amyloid beta peptide. Recent evidence suggests that sAPP has growth-promoting properties and may play a role in the formation of nerve cells (neurons) in the brain both before and after birth. Other functions of sAPP and amyloid beta peptide are under investigation.

How are changes in the APP gene related to health conditions?

Alzheimer disease - caused by mutations in the APP gene

More than 25 different mutations in the APP gene can cause early-onset Alzheimer disease. These mutations are responsible for 10 percent to 15 percent of all early-onset cases of the disorder.

The most common APP mutation changes one of the protein building blocks (amino acids) in the amyloid precursor protein. This mutation replaces the amino acid valine with the amino acid isoleucine at protein position 717 (written as Val717Ile or V717I). Mutations in the APP gene can lead to an increased amount of the amyloid beta peptide or to the production of a slightly longer and stickier form of the peptide. When these protein fragments are released from the cell, they can accumulate in the brain and form clumps called amyloid plaques. These plaques are characteristic of Alzheimer disease. A buildup of toxic amyloid beta peptide and amyloid plaques may lead to the death of neurons and the progressive signs and symptoms of this disorder.

other disorders - caused by mutations in the APP gene

Certain mutations in the APP gene can also result in brain abnormalities other than Alzheimer disease. For example, a particular APP mutation causes a disorder called hereditary cerebral hemorrhage with amyloidosis-Dutch type. This disorder is characterized by recurring episodes of bleeding in the brain (hemorrhagic strokes) that lead to the deterioration of memory, concentration, and judgment. Most people with this disorder develop signs and symptoms in mid-adulthood. The mutation that causes this disorder replaces the amino acid glutamic acid with the amino acid glutamine at position 22 of amyloid precursor protein (written as Glu22Gln or E22Q). The E22Q mutation likely affects processing of this protein, leading to the formation of amyloid plaques in brain tissue and the walls of blood vessels that serve the brain.

Where is the APP gene located?

Cytogenetic Location: 21q21

Molecular Location on chromosome 21: base pairs 26,174,731 to 26,465,002

The APP gene is located on the long (q) arm of chromosome 21 at position 21.

The APP gene is located on the long (q) arm of chromosome 21 at position 21.

More precisely, the APP gene is located from base pair 26,174,731 to base pair 26,465,002 on chromosome 21.

See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.

Where can I find additional information about APP?

You and your healthcare professional may find the following resources about APP helpful.

  • Educational resources - Information pages
    Basic Neurochemistry: Molecular, Cellular, and Medical Aspects (sixth edition, 2006): Alzheimer's Disease Is the Most Common Neurodegenerative Disorder (http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=bnchm.section.3282)
  • Gene Reviews - Clinical summary (http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=alzheimer-early)
  • Gene Tests - DNA tests ordered by healthcare professionals (http://www.genetests.org/query?testid=53438)

You may also be interested in these resources, which are designed for genetics professionals and researchers.

  • PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=PubMed&term=((APP[TI])+OR+(amyloid+beta+++precursor+protein[TI]))+AND+((Genes[MH])+OR+(Genetic+Phenomena[MH]))+AND+english[la]+AND+human[mh]&orig_db=PubMed&filters=ON&pmfilter_EDatLimit=1080+Days)
  • OMIM - Genetic disorder catalog
    • OMIM: APP gene (http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=104760)
    • OMIM: Hereditary Cerebral Hemorrhage with Amyloidosis-Dutch Type (http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=609065)
  • Research Resources - Tools for researchers
    • Alzheimer Disease & Frontotemporal Dementia Mutation Database (http://www.molgen.ua.ac.be/ADmutations/Default.cfm?MT=1&ML=1&Page=MutByQuery&Query=tblContexts.ID=3&Selection=Gene%20=%20APP)
    • Alzheimer Research Forum: AlzGene database (http://www.alzforum.org/res/com/gen/alzgene/geneoverview.asp?geneid=235)
    • Entrez Gene (http://view.ncbi.nlm.nih.gov/gene/351)
    • GeneCards (http://www.genecards.org/cgi-bin/carddisp?APP)
    • HUGO Gene Nomenclature Committee (http://www.genenames.org/data/hgnc_data.php?hgnc_id=620)

What other names do people use for the APP gene or gene products?

  • A4
  • A4_HUMAN
  • AAA
  • ABETA
  • ABPP
  • AD1
  • Amyloid A4 Protein Precursor
  • amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease)
  • amyloid beta-peptide
  • Amyloid Of Aging and Alzheimer Disease; AAA
  • amyloid precursor protein
  • APPI
  • Cerebral Vascular Amyloid Peptide
  • CVAP
  • PN-II
  • PreA4
  • protease nexin 2
  • Protease nexin-II

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What glossary definitions help with understanding APP?

acids ; amino acid ; amyloid ; amyloidosis ; amyloid plaque ; cell ; central nervous system ; cerebral hemorrhage ; enzyme ; gene ; hemorrhage ; hemorrhagic stroke ; isoleucine ; mutation ; nerve cell ; nervous system ; neuron ; peptide ; plaque ; protease ; protein ; sign ; soluble ; symptom ; tissue ; toxic ; vascular

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://ghr.nlm.nih.gov/glossary).

References
  • Bornebroek M, De Jonghe C, Haan J, Kumar-Singh S, Younkin S, Roos R, Van Broeckhoven C. Hereditary cerebral hemorrhage with amyloidosis Dutch type (AbetaPP 693): decreased plasma amyloid-beta 42 concentration. Neurobiol Dis. 2003 Dec;14(3):619-23. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=14678776)
  • Caille I, Allinquant B, Dupont E, Bouillot C, Langer A, Muller U, Prochiantz A. Soluble form of amyloid precursor protein regulates proliferation of progenitors in the adult subventricular zone. Development. 2004 May;131(9):2173-81. Epub 2004 Apr 08. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=15073156)
  • Conti L, Cattaneo E. Controlling neural stem cell division within the adult subventricular zone: an APPealing job. Trends Neurosci. 2005 Feb;28(2):57-9. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=15667924)
  • Cordy JM, Hooper NM, Turner AJ. The involvement of lipid rafts in Alzheimer's disease. Mol Membr Biol. 2006 Jan-Feb;23(1):111-22. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=16611586)
  • Edwards-Lee T, Ringman JM, Chung J, Werner J, Morgan A, St George Hyslop P, Thompson P, Dutton R, Mlikotic A, Rogaeva E, Hardy J. An African American family with early-onset Alzheimer disease and an APP (T714I) mutation. Neurology. 2005 Jan 25;64(2):377-9. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=15668448)
  • Fernandez-Madrid I, Levy E, Marder K, Frangione B. Codon 618 variant of Alzheimer amyloid gene associated with inherited cerebral hemorrhage. Ann Neurol. 1991 Nov;30(5):730-3. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=1763898)
  • Hardy J, Selkoe DJ. The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science. 2002 Jul 19;297(5580):353-6. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=12130773)
  • Harman D. Alzheimer's disease pathogenesis: role of aging. Ann N Y Acad Sci. 2006 May;1067:454-60. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=16804026)
  • Kerr ML, Small DH. Cytoplasmic domain of the beta-amyloid protein precursor of Alzheimer's disease: Function, regulation of proteolysis, and implications for drug development. J Neurosci Res. 2005 Jan 25; [Epub ahead of print]. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=15672415)
  • Levy E, Prelli F, Frangione B. Studies on the first described Alzheimer's disease amyloid beta mutant, the Dutch variant. J Alzheimers Dis. 2006;9(3 Suppl):329-39. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=16914871)
  • Maat-Schieman M, Roos R, van Duinen S. Hereditary cerebral hemorrhage with amyloidosis-Dutch type. Neuropathology. 2005 Dec;25(4):288-97. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=16382777)
  • Majersik JJ, Skalabrin EJ. Single-gene stroke disorders. Semin Neurol. 2006 Feb;26(1):33-48. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=16479442)
  • Papassotiropoulos A, Fountoulakis M, Dunckley T, Stephan DA, Reiman EM. Genetics, transcriptomics, and proteomics of Alzheimer's disease. J Clin Psychiatry. 2006 Apr;67(4):652-70. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=16669732)
  • Rocchi A, Pellegrini S, Siciliano G, Murri L. Causative and susceptibility genes for Alzheimer's disease: a review. Brain Res Bull. 2003 Jun 30; 61(1): 1-24. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=12788204)
  • Wolfe MS, Guénette SY. APP at a glance. J Cell Sci. 2007 Sep 15;120(Pt 18):3157-61. Review. No abstract available. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=17878232)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: December 2008
Published: January 23, 2009