Cited by 2,577Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Candidate gene for the chromosome 1 familial Alzheimer’s disease locus

Levy-Lahad, Ephrat, Wasco, Wilma, Poorkaj, Parvoneh, Romano, Donna M., Oshima, Junko, Pettingell, Warren H., Yu, Chang-en, Jondro, Paul D. +11 more·1995·Science

Abstract

A candidate gene for the chromosome 1 Alzheimer's disease (AD) locus was identified (STM2). The predicted amino acid sequence for STM2 is homologous to that of the recently cloned chromosome 14 AD gene (S182). A point mutation in STM2, resulting in the substitution of an isoleucine for an asparagine (N141l), was identified in affected people from Volga German AD kindreds. This N141l mutation occurs at an amino acid residue that is conserved in human S182 and in the mouse S182 homolog. The presence of missense mutations in AD subjects in two highly similar genes strongly supports the hypothesis that mutations in both are pathogenic.

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Crossref · 10.1126/science.7638622

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Authors
Levy-Lahad, E., Wasco, W., Poorkaj, P., Romano, D. M., Oshima, J., Pettingell, W. H., Yu, C.-E., Jondro, P. D., Schmidt, S. D., Wang, K., Crowley, A. C., Fu, Y.-H., Guenette, S. Y., Galas, D., Nemens, E., Wijsman, E. M., Bird, T. D., Schellenberg, G. D., & Tanzi, R. E.
Affiliations
  • Geriatric Research Education, and Clinical Center (182B), Veterans Affairs Medical Center, Seattle, WA 98108, USA.
  • Massachusetts General Hospital (US)
  • United States Department of Veterans Affairs (US)
  • Darwin Molecular, Bothell, WA 98021, USA.
  • Genetics and Aging Unit, Massachusetts General Hospital, Charlestown, MA 02129, USA.
  • University of Washington (US)
Venue
Science
Published
1995-08-18
Volume
269
Issue
5226
Pages
973-977
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W2083633251
Cited by
2,577
References
25
Citations by year
2026: 17 · 2025: 46 · 2024: 66 · 2023: 47 · 2022: 43 · 2021: 65 · 2020: 84 · 2019: 72 · 2018: 65 · 2017: 77 · 2016: 90 · 2015: 63 · 2014: 78 · 2013: 82 · 2012: 83
FWCI
99.06
Type
journal article
Language
en
Open access
closed
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r01ag011899-03)
  • National Institute on Aging (AG0513C, R01AG011762, R01 AG 11762, R01-AG11899)
Topics
  • Health Sciences › Medicine › Physiology › 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
familial Alzheimer's disease, candidate genes, missense mutations, gene homology, pathogenic variants
MeSH terms
Adult, Aged, Alzheimer Disease, Amino Acid Sequence, Base Sequence, Chromosome Mapping, Chromosomes, Human, Pair 1, Cloning, Molecular, Female, Germany, Humans, Lod Score, Male, Membrane Proteins, Middle Aged, Molecular Sequence Data, Mutation, Pedigree, Gene Expression, Point Mutation, DNA, Complementary, Presenilin-2

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