Exploring the etiology of Alzheimer disease using molecular genetics
Lendon CL, Ashall F, Goate AM.. JAMA, 1997-03-01
Topic: Amyloid, tau and blood-test diagnosis
Alzheimer disease (AD), the most common cause of dementia in the elderly, exists in both familial and sporadic forms. Genetic studies have led to the identification of 3 genes, beta-amyloid precursor protein (APP), presenilin-1 (PS1), and presenilin-2 (PS2), which, when mutated, can cause familial forms of AD. Mutations in each of these genes result in elevated levels of A beta42/43, a proteolytic processing fragment of APP that is deposited in brains of AD patients. Transgenic mice carrying AD-causing mutations in APP develop spontaneous age-related beta-amyloid (A beta) deposition and memory impairment. Genetic linkage and association studies have also shown that the epsilon4 allele of the apolipoprotein E (APOE) gene increases risk for AD in a dose-dependent manner in both familial and sporadic forms of AD and may account for as much as 50% of the attributable risk. APOE genotyping may be useful both as an adjunct to diagnosis and in identifying patient groups for therapeutic intervention. While the biological basis for the association of APOE epsilon4 with AD is not known, age of onset and A beta deposition are positively correlated with epsilon4 allele dosage in some cases, suggesting that this risk may also be mediated directly or indirectly through A beta. Because 50% of AD cases have no APOE epsilon4 alleles and families showing mendelian inheritance of AD exist in whom there are no mutations in any of the APP, PS1, or PS2 genes, it is likely that there are additional AD risk factors, both genetic and environmental, still to be identified.
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APA 7th
Lendon, C. L., Ashall, F., & Goate, A. M. (1997). Exploring the etiology of Alzheimer disease using molecular genetics. JAMA. https://doi.org/10.1001/jama.1997.03540340059034
Vancouver
Lendon CL, Ashall F, Goate AM. Exploring the etiology of Alzheimer disease using molecular genetics. JAMA. 1997. doi:10.1001/jama.1997.03540340059034. PMID: 9052714.
BibTeX
@article{lendon1997-9052714,
author = {Lendon, C. L. and Ashall, F. and Goate, A. M.},
title = {{Exploring the etiology of Alzheimer disease using molecular genetics}},
journal = {JAMA},
year = {1997},
doi = {10.1001/jama.1997.03540340059034},
pmid = {9052714},
url = {https://doi.org/10.1001/jama.1997.03540340059034}
}
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Key findings
- Mutations in each of these genes result in elevated levels of A beta42/43, a proteolytic processing fragment of APP that is deposited in brains of AD patients.
- Genetic linkage and association studies have also shown that the epsilon4 allele of the apolipoprotein E (APOE) gene increases risk for AD in a dose-dependent manner in both familial and sporadic forms of AD and may account for as much as 50% of the attributable risk.
- While the biological basis for the association of APOE epsilon4 with AD is not known, age of onset and A beta deposition are positively correlated with epsilon4 allele dosage in some cases, suggesting that this risk may also be mediated directly or indirectly through A beta.
Why it matters
This review describes how mutations in the APP, PS1, and PS2 genes can cause familial Alzheimer's disease by raising levels of the Aβ42/43 fragment, and how the APOE ε4 allele increases risk in a dose-dependent manner. It does not report a treatment or cure, but identifies genetic targets and notes that APOE genotyping may be useful as an adjunct to diagnosis and for identifying patient groups for therapeutic intervention.
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Study details
- Evidence strengthLow
How this study scored 48/100
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 (JAMA) |
| Journal's citation record | 4 / 4 | JAMA: journal h-index 1,011 (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 | 1997 — 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 | 5 / 7 | Cited 262 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 8.5 citations a year over 31 year(s) since 1997 |
| Impact for its field and year | 5 / 6 | Cited 23.5× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 5 other studies in this library |
| Still being cited | 1 / 4 | Cited 8 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Corinne L. Lendon: h-index 39 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Washington University in St. Louis: institution h-index 1,962 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 9052714) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 48 / 100 | — |
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