Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease
Alison Goate, Marie‐Christine Chartier‐Harlin, Mike Mullan, Jeremy Brown, Fiona Crawford, Liana Fidani, Luis A. Giuffra, Andrew R. Haynes et al.. Nature, 1991-02-21
Topic: Amyloid, tau and blood-test diagnosis
To avoid the problems that heterogeneity poses for genetic analysis, the researchers examined the cosegregation of Alzheimer's disease and markers along the long arm of chromosome 21 in a single family. They demonstrated that in this kindred, there is a point mutation in the amyloid precursor protein gene. Screening other cases of familial Alzheimer's disease revealed a second unrelated family in which this variant occurs, suggesting that some cases of the disease could be caused by mutations in this gene.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Goate, A., Chartier‐Harlin, M., Mullan, M., Brown, J., Crawford, F., Fidani, L., et al. (1991). Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease. Nature. https://doi.org/10.1038/349704a0
Vancouver
Goate A, Chartier‐Harlin M, Mullan M, Brown J, Crawford F, Fidani L, et al. Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease. Nature. 1991. doi:10.1038/349704a0. PMID: 1671712.
BibTeX
@article{goate1991-1671712,
author = {Goate, Alison and Chartier‐Harlin, Marie‐Christine and Mullan, Mike and Brown, Jeremy and Crawford, Fiona and Fidani, Liana and Giuffra, Luis A. and Haynes, Andrew R. and others},
title = {{Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease}},
journal = {Nature},
year = {1991},
doi = {10.1038/349704a0},
pmid = {1671712},
url = {https://doi.org/10.1038/349704a0}
}
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Key findings
- In this kindred, which shows linkage to chromosome 21 markers, there is a point mutation in the APP gene.
- This mutation causes an amino-acid substitution (Val----Ile) close to the carboxy terminus of the beta-amyloid peptide.
- Screening other cases of familial AD revealed a second unrelated family in which this variant occurs.
Why it matters
Reports that a missense mutation in the amyloid precursor protein gene tracks with familial Alzheimer's disease. Tying an inherited mutation to the disease identifies a gene to study, but no treatment follows from it directly.
New to this subject? Start with our plain-English guide: Genetics →
Study details
- Evidence strengthLow
How this study scored 63/100
Published in a top-tier journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 10 / 10 | Tier 1 — top-tier general journal (Nature) |
| Journal's citation record | 4 / 4 | Nature: journal h-index 1,841 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 1991 — older than 20 years, still counted |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 7 / 7 | Cited 4,676 times (OpenAlex, 2026-10-10) |
| Citations per year | 5 / 5 | 126.4 citations a year over 37 year(s) since 1991 |
| Impact for its field and year | 6 / 6 | Cited 145.4× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 5 / 6 | Cited by 174 other studies in this library |
| Still being cited | 4 / 4 | Cited 258 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author John Hardy: h-index 205 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Yale University: institution h-index 1,927 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 1671712) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 63 / 100 | — |
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