Cited by 163Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

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The presenilin genes: a new gene family involved in Alzheimer disease pathology

Cruts, Marc, Hendriks, Lydia, Van Broeckhoven, Christine·1996·Human Molecular Genetics

DOI 10.1093/hmg/5.supplement_1.1449

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Abstract

A positional cloning approach has led to the identification of two closely related genes, the presenilins (PS), for autosomal dominant presenile Alzheimer disease (AD): PS-1 at 14q24.3 and PS-2 at 1q31-q42. The PS-1 gene was identified by direct cDNA selection of yeast artificial chromosomes containing the candidate chromosomal region. Subsequently, the PS-2 gene was identified due to its high sequence homology with PS-1 and its location within the candidate region defined by linkage studies. To date, 30 different missense mutations and one in-frame splice site mutation were described in PS-1, while only two missense mutations were detected in PS-2, suggesting that PS-1 mutations are more frequently involved in familial presenile AD. The PS transcripts encode novel proteins that resemble integral transmembrane proteins of roughly 450 amino acids and at least seven transmembrane domains. The genomic organization of the PS genes is very similar showing that full length PS-1 and PS-2 are encoded by 10 exons. However, different alternative splicing patterns have been observed for PS-1 and PS-2 indicating that the corresponding proteins (ps-1 and ps-2) may have similar but not identical biological functions.

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Perez-Tur, 1996, Presenilin-1 polymorphism and Alzheimer's disease, Lancet, 347, 1560, 10.1016/S0140-6736(96)90716-3 · DOI

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Authors: Cruts, M., Hendriks, L., & Van Broeckhoven, C.
Affiliations: University of Antwerp (BE)
ORCID: Cruts, Marc
Venue: Human Molecular Genetics
Publisher: Oxford University Press (OUP)
Published: 1996-09
Volume: 5
Issue: Supplement_1
Pages: 1449-1455
ISSN: 0964-6906 (ISSN-L)
1460-2083
DOI: 10.1093/hmg/5.supplement_1.1449
OpenAlex: W2121823413
Cited by: 163
References: 59
Citations by year: 2026: 1 · 2024: 3 · 2023: 3 · 2022: 3 · 2021: 1 · 2020: 2 · 2019: 1 · 2018: 2 · 2017: 5 · 2016: 2 · 2015: 4 · 2014: 6 · 2013: 7 · 2012: 1
FWCI: 4.66
Type: journal article
Language: en
Open access: closed
Locations: Human Molecular Genetics (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords: presenilin 1, presenilin 2, familial Alzheimer's disease, positional cloning, missense mutations, splice site mutation, transmembrane proteins, alternative splicing, gene family, yeast artificial chromosomes, cDNA selection, linkage mapping
MeSH terms: Alzheimer Disease, Amino Acid Sequence, Animals, Cloning, Molecular, Humans, Membrane Proteins, Molecular Sequence Data, Mutation, Gene Expression, Sequence Homology, Amino Acid, Presenilin-1, Presenilin-2

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The presenilin genes: a new gene family involved in Alzheimer disease pathology

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