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PSEN1

Reviewed December 2008

What is the official name of the PSEN1 gene?

The official name of this gene is “presenilin 1.”

PSEN1 is the gene's official symbol. The PSEN1 gene is also known by other names, listed below.

What is the normal function of the PSEN1 gene?

The PSEN1 gene provides instructions for making a protein called presenilin 1. This protein is involved in the development of the brain and spinal cord (central nervous system) and the survival of nerve cells (neurons). Presenilin 1 helps process proteins that transmit chemical signals from the cell membrane into the nucleus. Once in the nucleus, these signals turn on (activate) genes that are important for cell growth and maturation.

Presenilin 1 is best known for its role in processing amyloid precursor protein, which is made in the brain and other tissues. Research suggests that presenilin 1 works together with other enzymes to cut amyloid precursor protein into smaller segments (peptides). One of these peptides is called soluble amyloid precursor protein (sAPP), and another is called amyloid beta peptide. Recent evidence suggests that sAPP has growth-promoting properties and may play a role in the formation of 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 PSEN1 gene related to health conditions?

Alzheimer disease - caused by mutations in the PSEN1 gene

More than 150 PSEN1 mutations have been identified in patients with early-onset Alzheimer disease. Mutations in the PSEN1 gene are the most common cause of early-onset Alzheimer disease, accounting for up to 70 percent of cases.

Almost all PSEN1 mutations change single building blocks of DNA (nucleotides) in a particular segment of the PSEN1 gene. These mutations result in the production of an abnormal presenilin 1 protein. Defective presenilin 1 disrupts the processing of amyloid precursor protein, leading to the overproduction of amyloid beta peptide. This protein fragment can build up in the brain and form clumps called amyloid plaques that 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.

Where is the PSEN1 gene located?

Cytogenetic Location: 14q24.3

Molecular Location on chromosome 14: base pairs 72,672,931 to 72,756,861

The PSEN1 gene is located on the long (q) arm of chromosome 14 at position 24.3.

The PSEN1 gene is located on the long (q) arm of chromosome 14 at position 24.3.

More precisely, the PSEN1 gene is located from base pair 72,672,931 to base pair 72,756,861 on chromosome 14.

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 PSEN1?

You and your healthcare professional may find the following resources about PSEN1 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=53441)

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=((PSEN1[TI])+OR+(presenilin+1[TI]))+AND+((Genes[MH])+OR+(Genetic+Phenomena[MH]))+AND+english[la]+AND+human[mh]&orig_db=PubMed&filters=ON&pmfilter_EDatLimit=720+Days)
  • OMIM - Genetic disorder catalog (http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=104311)
  • 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=1&Selection=Gene%20=%20PSEN1)
    • Alzheimer Research Forum: AlzGene database (http://www.alzforum.org/res/com/gen/alzgene/geneoverview.asp?geneid=84)
    • Entrez Gene (http://view.ncbi.nlm.nih.gov/gene/5663)
    • GeneCards (http://www.genecards.org/cgi-bin/carddisp?PSEN1)
    • HUGO Gene Nomenclature Committee (http://www.genenames.org/data/hgnc_data.php?hgnc_id=9508)

What other names do people use for the PSEN1 gene or gene products?

  • AD3
  • FAD
  • presenilin 1 (Alzheimer disease 3)
  • presenilin 1 protein
  • PS1
  • PSN1_HUMAN
  • PSNL1 gene product
  • S182 protein

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 PSEN1?

amyloid ; amyloid plaque ; cell ; cell membrane ; central nervous system ; DNA ; enzyme ; gene ; gene product ; mutation ; nerve cell ; nervous system ; neuron ; nucleotide ; nucleus ; peptide ; plaque ; protein ; sign ; soluble ; symptom ; tissue ; toxic

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

References
  • Bertram L, Tanzi RE. The current status of Alzheimer's disease genetics: what do we tell the patients? Pharmacol Res. 2004 Oct;50(4):385-96. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=15304236)
  • 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)
  • Das HK. Transcriptional regulation of the presenilin-1 gene: implication in Alzheimer's disease. Front Biosci. 2008 Jan 1;13:822-32. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=17981591)
  • George-Hyslop PS, Rossor M. Alzheimer's disease. Unravelling the disease process. Lancet. 2001 Dec;358 Suppl:S1. No abstract available. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=11784550)
  • 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)
  • Larner AJ, Doran M. Clinical phenotypic heterogeneity of Alzheimer's disease associated with mutations of the presenilin-1 gene. J Neurol. 2006 Feb;253(2):139-58. Epub 2005 Nov 4. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=16267640)
  • 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)
  • Selkoe DJ. Alzheimer's disease: genes, proteins, and therapy. Physiol Rev. 2001 Apr;81(2):741-66. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=11274343)
  • St George-Hyslop PH. Genetic factors in the genesis of Alzheimer's disease. Ann N Y Acad Sci. 2000;924:1-7. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=11193785)
  • Thinakaran G, Parent AT. Identification of the role of presenilins beyond Alzheimer's disease. Pharmacol Res. 2004 Oct;50(4):411-8. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=15304238)

 

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