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Apolipoprotein E genotype and deposits of Abeta40 and Abeta42 in Alzheimer disease
McNamara MJ, Gomez-Isla T, Hyman BT.. Archives of neurology, 1998-07-01
Topic: Amyloid, tau and blood-test diagnosis
Objective To examine the differential deposition of amyloid beta (Abeta) peptide isoforms Abeta40 and Abeta42 in the Alzheimer disease (AD) brain in relation to the apolipoprotein E (APOE) genotype. Background The APOE epsilon4 genotype is an inherited risk factor for AD and is associated with increased deposition of Abeta protein in the cerebral cortex. Previous data from familial AD due to mutations in presenilin 1 and presenilin 2 genes and the amyloid precursor protein suggest that the long form of Abeta peptide, Abeta42, is selectively increased in these circumstances. Herein, we examine whether APOE genotype influenced the species of Abeta peptide deposited. Design and methods The amount of Abeta40, Abeta42, and total Abeta deposited in immunostained temporal lobe tissue of 28 cases of AD of known APOE genotype was determined. Results Individuals with the APOE epsilon4 genotype (APOE epsilon4/4) were associated with both increased Abeta40 (P Conclusion Our results differ from the data from AD due to mutations in presenilin 1 and presenilin 2 genes and the amyloid precursor protein and suggest that the APOE epsilon4 genotype mediates increased Abeta deposition by a mechanism that differs from that found in other genetic causes of AD.
Key findings
- Background The APOE epsilon4 genotype is an inherited risk factor for AD and is associated with increased deposition of Abeta protein in the cerebral cortex.
- Previous data from familial AD due to mutations in presenilin 1 and presenilin 2 genes and the amyloid precursor protein suggest that the long form of Abeta peptide, Abeta42, is selectively increased in these circumstances.
- Results Individuals with the APOE epsilon4 genotype (APOE epsilon4/4) were associated with both increased Abeta40 (P<.05) and Abeta42 (P<.05) compared with individuals without the APOE epsilon4/4 genotype.
Why it matters
Examining temporal lobe brain tissue from 28 people with Alzheimer's, researchers found that carrying two copies of the APOE epsilon4 risk gene was associated with more Abeta40 deposits. The pattern differed from that seen in Alzheimer's caused by presenilin 1, presenilin 2 or amyloid precursor protein mutations. The authors suggest APOE epsilon4 raises amyloid buildup through a different mechanism than these other genetic causes, which helps explain disease biology rather than offering a therapy.
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Study details
- Study designclinical trial
- Evidence strengthLow
How this study scored 43/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Archives of neurology) |
| Journal's citation record | 3 / 4 | Archives of Neurology: journal h-index 353 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | Design recorded as “clinical trial”, which our rubric does not rank (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 | 1998 — 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 | 3 / 3 | Studied in people (pubmed indexes it as a clinical or observational study) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 4 / 7 | Cited 55 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 1.8 citations a year over 30 year(s) since 1998 |
| Impact for its field and year | 3 / 6 | Cited 3.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 7 other studies in this library |
| Still being cited | 0 / 4 | Cited 0 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Bradley T. Hyman: h-index 190 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Massachusetts General Hospital: institution h-index 2,057 (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 9678319) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 43 / 100 | — |
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
APA 7th
McNamara, M. J., Gomez-Isla, T., & Hyman, B. T. (1998). Apolipoprotein E genotype and deposits of Abeta40 and Abeta42 in Alzheimer disease. Archives of neurology. https://doi.org/10.1001/archneur.55.7.1001
Vancouver
McNamara MJ, Gomez-Isla T, Hyman BT. Apolipoprotein E genotype and deposits of Abeta40 and Abeta42 in Alzheimer disease. Archives of neurology. 1998. doi:10.1001/archneur.55.7.1001. PMID: 9678319.
BibTeX
@article{mcnamara1998-9678319,
author = {McNamara, M. J. and Gomez-Isla, T. and Hyman, B. T.},
title = {{Apolipoprotein E genotype and deposits of Abeta40 and Abeta42 in Alzheimer disease}},
journal = {Archives of neurology},
year = {1998},
doi = {10.1001/archneur.55.7.1001},
pmid = {9678319},
url = {https://doi.org/10.1001/archneur.55.7.1001}
}
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