Cited by 4,051Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease

Sherrington, R., Rogaev, E. I., Liang, Y., Rogaeva, E. A., Levesque, G., Ikeda, M., Chi, H., Lin, C. +25 more·1995·Nature

Abstract

Some cases of Alzheimer's disease are inherited as an autosomal dominant trait. Genetic linkage studies have mapped a locus (AD3) associated with susceptibility to a very aggressive form of Alzheimer's disease to chromosome 14q24.3. We have defined a minimal cosegregating region containing the AD3 gene, and isolated at least 19 different transcripts encoded within this region. One of these transcripts (S182) corresponds to a novel gene whose product is predicted to contain multiple transmembrane domains and resembles an integral membrane protein. Five different missense mutations have been found that cosegregate with early-onset familial Alzheimer's disease. Because these changes occurred in conserved domains of this gene, and are not present in normal controls, they are likely to be causative of AD3.

Integrity signals

Registry

Crossref · 10.1038/375754a0

Cites

48 of 48 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Early onset Alzheimer's disease can be caused by mutations in the APP, presenilin 1, and presenilin 2 genes.

    “Early onset Alzheimer's disease can be caused by mutations in the APP (Chartier-Harlin et al., 1991;Goate et al., 1991;Murrell et al., 1991;Mullan et al., 1992), presenilin 1 (PS1) (Sherrington et al., 1995), and presenilin 2 (PS2) (Levy-Lahad et al., 1995) genes.”
  • The amyloid cascade hypothesis is strongly supported by neuropathological and human genetic evidence.

    “The amyloid cascade hypothesis of Alzheimer disease (AD), which proposes that deposition of the amyloid-β (Aβ) peptide in the brain is a central event in disease pathology (Figure 1), is strongly supported by neuropathological and human genetic evidence”

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Sherrington, R., Rogaev, E. I., Liang, Y., Rogaeva, E. A., Levesque, G., Ikeda, M., Chi, H., Lin, C., Li, G., Holman, K., Tsuda, T., Mar, L., Foncin, J.-F., Bruni, A. C., Montesi, M. P., Sorbi, S., Rainero, I., Pinessi, L., Nee, L., Chumakov, I., Pollen, D., Brookes, A., Sanseau, P., Polinsky, R. J., Wasco, W., Da Silva, H. A. R., Haines, J. L., Pericak-Vance, M. A., Tanzi, R. E., Roses, A. D., Fraser, P. E., Rommens, J. M., & St George-Hyslop, P. H.
Affiliations
  • University of Toronto (CA)
  • Inserm (FR)
  • University of Florence (IT)
  • University of Turin (IT)
  • National Institutes of Health (US)
  • Fondation Jean Dausset-CEPH (FR)
  • University of Massachusetts Chan Medical School (US)
  • Western General Hospital (GB)
  • Sandoz Group AG (Switzerland) (CH)
  • Harvard University (US)
  • Duke University (US)
Venue
Nature
Published
1995-06
Volume
375
Issue
6534
Pages
754-760
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
OpenAlex
W2046209489
Cited by
4,051
References
48
Citations by year
2026: 36 · 2025: 70 · 2024: 78 · 2023: 54 · 2022: 93 · 2021: 93 · 2020: 118 · 2019: 107 · 2018: 105 · 2017: 116 · 2016: 140 · 2015: 100 · 2014: 132 · 2013: 120 · 2012: 134
FWCI
144.01
Type
journal article
Language
en
Open access
closed
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • UCL Discovery (University College London) (submittedVersion)
  • Florence Research (University of Florence) (submittedVersion)
  • Institutional Research Information System University of Turin (University of Turin) (submittedVersion)
Funders
Canadian Institutes of Health Research (64309)
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
early-onset familial Alzheimer's disease, missense mutations, autosomal dominant inheritance, gene cloning, co-segregation, transmembrane proteins, novel genes, susceptibility genes
MeSH terms
Alzheimer Disease, Amino Acid Sequence, Animals, Base Sequence, Chromosome Mapping, Chromosomes, Human, Pair 14, Cloning, Molecular, Female, Humans, Male, Membrane Proteins, Molecular Sequence Data, Mutation, Pedigree, Transcription, Genetic, Open Reading Frames, Protein Structure, Secondary, Mice, Presenilin-1

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review