Topic: Amyloid, tau and blood-test diagnosis
Alzheimer disease (AD)-like neuropathology increases progressively during aging in most primates, and, in some species, is concurrent with reproductive decline in females and cognitive impairments. We consider how the schedule of AD may have evolved in early humans in relation to the apolipoprotein E (apoE) allele system, which is not found in other primates, and to the increasing duration of postnatal care. The delay of independence and the increasing length of maturation required that the schedule of AD-like neurodegeneration be slowed, otherwise parental caregivers would already have become impaired. We hypothesize that the uniquely human apoE epsilon3 allele evolved from the epsilon4 of primate ancestors during human evolution in relation to the rapid increases of brain size and the emergence of grandmothering. In discussing theses possibilities, we review the diverse bioactivities of apoE, which include involvement in hormone systems. The evolution of menopause is also considered in relation to the protective effect of estrogen on AD.
Key findings
- We consider how the schedule of AD may have evolved in early humans in relation to the apolipoprotein E (apoE) allele system, which is not found in other primates, and to the increasing duration of postnatal care.
- The delay of independence and the increasing length of maturation required that the schedule of AD-like neurodegeneration be slowed, otherwise parental caregivers would already have become impaired.
- We hypothesize that the uniquely human apoE epsilon3 allele evolved from the epsilon4 of primate ancestors during human evolution in relation to the rapid increases of brain size and the emergence of grandmothering.
- In discussing theses possibilities, we review the diverse bioactivities of apoE, which include involvement in hormone systems.
- The evolution of menopause is also considered in relation to the protective effect of estrogen on AD.
Why it matters
This paper hypothesizes that the uniquely human APOE ε3 allele evolved from the ε4 allele of primate ancestors in relation to increasing brain size and the emergence of grandmothering. It proposes that the schedule of Alzheimer's-like neurodegeneration had to slow so that parental caregivers would not become impaired.
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Study details
- Evidence strengthLow
How this study scored 46/100
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 (Neurobiology of aging) |
| Journal's citation record | 3 / 4 | Neurobiology of Aging: journal h-index 263 (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 | 1999 — 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 206 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 7.1 citations a year over 29 year(s) since 1999 |
| Impact for its field and year | 3 / 6 | Cited 3.8× 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 | 2 / 4 | Cited 17 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Robert Morris Sapolsky: h-index 120 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Stanford University: institution h-index 2,684 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 10604433) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 46 / 100 | — |
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Read the original
May need a subscription Unpaywall, Europe PMC and OpenAlex found no free copy of the full text (checked 10 Oct 2026), so the publisher may charge for it. The PubMed abstract is free.
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
Finch, C. E., & Sapolsky, R. M. (1999). The evolution of Alzheimer disease, the reproductive schedule, and apoE isoforms. Neurobiology of aging. https://doi.org/10.1016/s0197-4580(99)00053-6
Vancouver
Finch CE, Sapolsky RM. The evolution of Alzheimer disease, the reproductive schedule, and apoE isoforms. Neurobiology of aging. 1999. doi:10.1016/s0197-4580(99)00053-6. PMID: 10604433.
BibTeX
@article{finch1999-10604433,
author = {Finch, C. E. and Sapolsky, R. M.},
title = {{The evolution of Alzheimer disease, the reproductive schedule, and apoE isoforms}},
journal = {Neurobiology of aging},
year = {1999},
doi = {10.1016/s0197-4580(99)00053-6},
pmid = {10604433},
url = {https://doi.org/10.1016/s0197-4580(99)00053-6}
}
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