Apolipoprotein E and Alzheimer disease: an update on genetic and functional analyses
Saunders AM.. Journal of neuropathology and experimental neurology, 2000-09-01
Topic: Amyloid, tau and blood-test diagnosis
Exceptional advances have been made in understanding the genetics of how common polymorphisms of the apolipoprotein E gene influence the risk and age of onset of Alzheimer disease (AD). The major genetic susceptibility locus for the common forms of AD, there are 3 common alleles, designated epsilon2, epsilon3, and epsilon4. The inheritance of each dose of APOE4 increases the risk of disease and decreases the age of onset; conversely, the APOE2 allele appears to be protective, by lowering the risk of disease and increasing the age of onset. Testing for the APOE4 allele can be a clinically useful tool in the early diagnosis of cognitively impaired patients suspected of having AD. The APOE4 allele also negatively influences functional recovery following a variety of brain insults. What remains in the study of apolipoprotein E is an explanation of how minor changes in a protein can produce such striking differences in risk and age of onset. In vitro and animal model studies strongly suggest that brain apolipoprotein E is a multifunctional molecule, with potential roles in amyloid deposition and clearance, microtubule stability, intracellular signaling, immune modulation, glucose metabolism, oxidative stress, and other cellular processes. While the relevance of these proposed functions to the etiology of AD remains a mystery, these and other hypotheses will be tested as the field of apoE neurobiology grows, adding relevant new data to the functions of apoE in health and in the pathogenic mechanisms leading to AD.
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APA 7th
Saunders, A. M. (2000). Apolipoprotein E and Alzheimer disease: an update on genetic and functional analyses. Journal of neuropathology and experimental neurology. https://doi.org/10.1093/jnen/59.9.751
Vancouver
Saunders AM. Apolipoprotein E and Alzheimer disease: an update on genetic and functional analyses. Journal of neuropathology and experimental neurology. 2000. doi:10.1093/jnen/59.9.751. PMID: 11005255.
BibTeX
@article{saunders2000-11005255,
author = {Saunders, A. M.},
title = {{Apolipoprotein E and Alzheimer disease: an update on genetic and functional analyses}},
journal = {Journal of neuropathology and experimental neurology},
year = {2000},
doi = {10.1093/jnen/59.9.751},
pmid = {11005255},
url = {https://doi.org/10.1093/jnen/59.9.751}
}
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Key findings
- In vitro and animal model studies strongly suggest that brain apolipoprotein E is a multifunctional molecule, with potential roles in amyloid deposition and clearance, microtubule stability, intracellular signaling, immune modulation, glucose metabolism, oxidative stress, and other cellular processes.
Why it matters
This review describes how the APOE gene has three common forms, with each copy of APOE4 raising Alzheimer's risk and lowering the age of onset, while APOE2 appears protective. It notes that testing for APOE4 can help in early diagnosis, but how such small protein changes produce these effects remains unexplained, and much of the evidence for APOE's many possible roles comes from laboratory and animal studies.
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Study details
- Evidence strengthLow
How this study scored 40/100
Published in a peer-reviewed 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 | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of neuropathology and experimental neurology) |
| Journal's citation record | 2 / 4 | Journal of Neuropathology & Experimental Neurology: journal h-index 239 (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 | 2000 — 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 148 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 5.3 citations a year over 28 year(s) since 2000 |
| Impact for its field and year | 3 / 6 | Cited 8.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 8 other studies in this library |
| Still being cited | 1 / 4 | Cited 6 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Ann M. Saunders: h-index 72 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Duke Medical Center: institution h-index 1,255 (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 11005255) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 40 / 100 | — |
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