Apolipoprotein E4 allele as a predictor of cholinergic deficits and treatment outcome in Alzheimer disease
Poirier J, Delisle MC, Quirion R, Aubert I, Farlow M, Lahiri D, Hui S, Bertrand P et al.. Proceedings of the National Academy of Sciences of the United States of America, 1995-12-01
Topic: Amyloid, tau and blood-test diagnosis
Apolipoprotein E (apoE) is critical in the modulation of cholesterol and phospholipid transport between cells of different types. Human apoE is a polymorphic protein with three common alleles, APO epsilon 2, APO epsilon 3, and APO epsilon 4. ApoE4 is associated with sporadic and late-onset familial Alzheimer disease (AD). Gene dose was shown to have an effect on risk of developing AD, age of onset, accumulation of senile plaques in the brain, and reduction of choline acetyltransferase (ChAT) activity in the hippocampus of AD subjects. To characterize the possible impact of the apoE4 allele on cholinergic markers in AD, we examined the effect of apoE4 allele copy number on pre- and postsynaptic markers of cholinergic activity. ApoE4 allele copy number showed an inverse relationship with residual brain ChAT activity and nicotinic receptor binding sites in both the hippocampal formation and the temporal cortex of AD subjects. AD cases lacking the apoE4 allele showed ChAT activities close or within age-matched normal control values. The effect of the apoE4 allele on cholinomimetic drug responsiveness was assessed next in a group (n = 40) of AD patients who completed a double-blind, 30-week clinical trial of the cholinesterase inhibitor tacrine. Results showed that > 80% of apoE4-negative AD patients showed marked improvement after 30 weeks as measured by the AD assessment scale (ADAS), whereas 60% of apoE4 carriers had ADAS scores that were worse compared to baseline. These results strongly support the concept that apoE4 plays a crucial role in the cholinergic dysfunction associated with AD and may be a prognostic indicator of poor response to therapy with acetylcholinesterase inhibitors in AD patients.
Key findings
- ApoE4 is associated with sporadic and late-onset familial Alzheimer disease (AD).
- Results showed that > 80% of apoE4-negative AD patients showed marked improvement after 30 weeks as measured by the AD assessment scale (ADAS), whereas 60% of apoE4 carriers had ADAS scores that were worse compared to baseline.
- These results strongly support the concept that apoE4 plays a crucial role in the cholinergic dysfunction associated with AD and may be a prognostic indicator of poor response to therapy with acetylcholinesterase inhibitors in AD patients.
Why it matters
This study found that the number of APOE epsilon 4 alleles was linked to lower cholinergic markers in the brains of people with Alzheimer's disease. In a small tacrine trial, most APOE epsilon 4-negative patients improved while most carriers worsened, suggesting the allele may predict poor response to this type of therapy.
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Study details
- Participants40
- Evidence strengthLow
How this study scored 51/100
Published in a peer-reviewed journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Proceedings of the National Academy of Sciences of the United States of America) |
| Journal's citation record | 4 / 4 | Proceedings of the National Academy of Sciences: journal h-index 1,167 (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 | 1995 — older than 20 years, still counted |
| Sample size | 1 / 4 | 40 participants |
| 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 (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 599 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 18.2 citations a year over 33 year(s) since 1995 |
| Impact for its field and year | 5 / 6 | Cited 21.6× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 14 other studies in this library |
| Still being cited | 1 / 4 | Cited 13 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Brian Mark Gilfix: h-index 27 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | McGill University: institution h-index 1,373 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 8618881) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 51 / 100 | — |
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Read the original
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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APA 7th
Poirier, J., Delisle, M. C., Quirion, R., Aubert, I., Farlow, M., Lahiri, D., et al. (1995). Apolipoprotein E4 allele as a predictor of cholinergic deficits and treatment outcome in Alzheimer disease. Proceedings of the National Academy of Sciences of the United States of America. https://doi.org/10.1073/pnas.92.26.12260
Vancouver
Poirier J, Delisle MC, Quirion R, Aubert I, Farlow M, Lahiri D, et al. Apolipoprotein E4 allele as a predictor of cholinergic deficits and treatment outcome in Alzheimer disease. Proceedings of the National Academy of Sciences of the United States of America. 1995. doi:10.1073/pnas.92.26.12260. PMID: 8618881.
BibTeX
@article{poirier1995-8618881,
author = {Poirier, J. and Delisle, M. C. and Quirion, R. and Aubert, I. and Farlow, M. and Lahiri, D. and Hui, S. and Bertrand, P. and others},
title = {{Apolipoprotein E4 allele as a predictor of cholinergic deficits and treatment outcome in Alzheimer disease}},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
year = {1995},
doi = {10.1073/pnas.92.26.12260},
pmid = {8618881},
url = {https://doi.org/10.1073/pnas.92.26.12260}
}
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