PSEN1

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.

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.