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PSEN1 gene

Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Gene

PSEN1 gene

The PSEN1 gene provides instructions for making the presenilin 1 protein, a critical component of the gamma-secretase complex involved in cell signaling and protein processing.

Normal Function

The PSEN1 gene provides instructions for making a protein called presenilin 1. This protein is one subunit of a complex called gamma- (γ-) secretase. Presenilin 1 carries out the major function of the complex, which is to cut apart (cleave) other proteins into smaller pieces called peptides. This process is called proteolysis, and presenilin 1 is described as the proteolytic subunit of γ-secretase.

The γ-secretase complex is located in the membrane that surrounds cells, where it cleaves many different transmembrane proteins. This cleavage is an important step in several chemical signaling pathways that transmit signals from outside the cell into the nucleus. One of these pathways, known as Notch signaling, is essential for the normal growth and maturation (differentiation) of hair follicle cells and other types of skin cells. Notch signaling is also involved in normal immune system function.

The γ-secretase complex may be best known for its role in processing amyloid precursor protein (APP), which is made in the brain and other tissues. γ-secretase cuts APP into smaller peptides, including soluble amyloid precursor protein (sAPP) and several versions of amyloid-beta (β) peptide. 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.

Health Conditions Related to Genetic Changes

Alzheimer's disease

Dozens of PSEN1 gene variants (mutations) have been identified in patients with early-onset Alzheimer's disease, a degenerative brain condition that begins before age 65. Variants in the PSEN1 gene are the most common cause of early-onset Alzheimer's disease, accounting for up to 70 percent of cases.

Almost all PSEN1 gene variants result in the production of an abnormal presenilin 1 protein. Defective presenilin 1 interferes with the function of the γ-secretase complex, which alters the processing of APP and leads to the overproduction of a longer, toxic version of amyloid-β peptide. These protein fragments build up in the brain, forming clumps called amyloid plaques, which are a characteristic feature of Alzheimer's disease and likely lead to the death of neurons.

Hidradenitis suppurativa

At least one variant in the PSEN1 gene has been found to cause hidradenitis suppurativa, a chronic skin disease characterized by recurrent boil-like lumps (nodules) under the skin that develop in hair follicles. These nodules tend to become inflamed and painful, producing significant scarring as they heal.

  • The identified variant (725delC) reduces the amount of functional presenilin 1, leading to a shortage of the γ-secretase complex.
  • This shortage impairs cell signaling pathways, including Notch signaling.
  • Studies suggest that abnormal Notch signaling may promote the development of recurrent nodules in hair follicles and trigger skin inflammation.

Other Names for This Gene

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

Frequently Asked Questions

PSEN1 mutations are associated with autosomal dominant early-onset familial Alzheimer's disease, which typically begins between the ages of 30 and 50, significantly earlier than the sporadic form that usually appears after age 65. The progression of symptoms in PSEN1-related cases can be more rapid and severe compared to late-onset cases. Because the inheritance pattern is dominant, having one copy of the mutated gene is enough to cause the disease, meaning there is a 50 percent chance of passing it to each child.
Genetic testing for PSEN1 is generally not recommended for asymptomatic individuals unless they are considering predictive testing for themselves or their children. This is because there is currently no cure or treatment that can prevent the disease from developing, and a positive result can cause significant psychological distress. Clinicians usually recommend comprehensive genetic counseling before and after testing to help individuals understand the implications and prepare for potential outcomes. Testing is more commonly considered in research settings or for individuals who have already developed symptoms to confirm the diagnosis.
Early signs often include noticeable and rapid changes in memory, particularly for recent events, that interfere with daily life. Unlike normal age-related forgetfulness, individuals with PSEN1 mutations may experience difficulty finding words, getting lost in familiar places, or struggling with complex tasks like managing finances or planning meals. Other early indicators can include changes in mood, such as increased anxiety, depression, or apathy, and a loss of initiative. If these changes are progressive and affect functional independence, a medical evaluation is warranted.
Currently, there are no proven lifestyle changes or medications that can stop or reverse the progression of PSEN1-related Alzheimer's disease. However, maintaining a healthy lifestyle, including regular physical activity, a balanced diet, and social engagement, may help support overall brain health and potentially delay the onset of symptoms in some individuals. Medications such as cholinesterase inhibitors and memantine can help manage symptoms and improve quality of life for a period of time, but they do not alter the underlying genetic cause or halt disease progression. Research into disease-modifying therapies is ongoing.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.