PSEN1

A gene on chromosome 14q24.3 that encodes a probable catalytic subunit of the gamma-secretase complex, which catalyses the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP. It may play a role in intracellular signalling and gene expression, and in linking chromatin to the nuclear membrane. PSEN1 stimulates cell–cell adhesion by associating with the E-cadherin/catenin complex; it cleaves E-cadherin during apoptosis or calcium influx, promoting the disassembly of the E-cadherin/catenin complex and increases the pool of cytoplasmic beta-catenin, thus downregulating Wnt signalling. It may play a role in haematopoiesis.

Molecular pathology
Defects in PSEN1 cause of Alzheimer disease type 3, frontotemporal dementia, cardiomyopathy dilated type 1U, and familial acne inversa type 3.

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References in periodicals archive

The researchers generated induced pluripotent stem (iPS) cells from affected and unaffected individuals from two families carrying PSEN1 mutations.

14 new gene targets in Alzheimer sufferers identified

Ringman reported that 159 were at risk for PSEN1 mutations, 19 for PSEN2 mutations, and 34 for APP mutations.

Subtle changes in behavior may signal progression to AD

Mutations in three dominant genes (PSEN1, PSEN2 and APP) were shown to account for increased risk in early-onset AD (Levy-Lahad, Lahad, Wijsman, Bird, & Schellenberg, 1995; Sherrington et al., 1995; Sleegers & van Duijn, 2001; Tanzi & Bertram, 2001).

African Americans and Alzheimer's disease: role of health educators in addressing this silent epidemic

Genetic markers associated with autosomal dominant early-onset (typically occurs before the age of 65 years) familial AD include mutations in the amyloid precursor protein (APP) gene and in the genes for presenilin 1 and 2 (PSEN1 and PSEN2), proteins that make up part of the secretase protein complex.

State of the science: use of biomarkers and imaging in diagnosis and management of Alzheimer disease

A team of scientists from Cardiff University have been examining three genes - APP, PSEN1 and PSEN2 - which are known to cause rare early onset forms of Alzheimer's.

Cardiff scientists in Alzheimer's discovery

The genetic component is most conspicuous in a relatively small percentage (< 1%) of families that carry disease-causing germline mutations in 1 of 3 genes--APP [amyloid beta (A4) precursor protein], PSEN1 (presenilin 1), or PSEN2 (presenilin 2)--that will invariably lead to AD, often at a relatively young age.

Alzheimer disease: advances in pathogenesis, diagnosis, and therapy

George-Hyslop et al., 1987), the Presenilin I (PSEN1) gene on chromosome 14 (Mullan et al., 1992; Schellenberg et al., 1992; St.

The clinical utility of genetic information in the care of persons with Alzheimer's disease

Quiroz, Ph.D., from Massachusetts General Hospital in Boston, and colleagues assessed measures of carbon 11-labeled Pittsburgh Compound B positron emission tomography (PET) and flortaucipir F18 PET imaging in 24 presenilin 1 (PSEN1) E280A autosomal dominant AD kindred members including 12 carriers (nine cognitively unimpaired; three with mild cognitive impairment) and 12 cognitively unimpaired noncarriers.

Molecular Markers May ID Alzheimer's Before Clinical Onset; Amyloid-positive PSEN1 E280A mutation carriers have elevated levels of tau deposition before onset

Neurons derived from iPSCs generated from familial AD (fAD) patients carrying mutations in genes encoding amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2) provide an innovative tool to elucidate AD etiology and develop efficient therapeutics.

Generation of Cholinergic and Dopaminergic Interneurons from Human Pluripotent Stem Cells as a Relevant Tool for In Vitro Modeling of Neurological Disorders Pathology and Therapy