Topic: Brain proteins, microglia and lab models
Abstract The genetic origin of the three common variants of the human apolipoprotein E (apoE) protein, known as E2, E3 and E4, was understood in 1981, and since the mid 1980s these are probably the most-studied protein variants in human races. They have been related to a number of age-related diseases, including Alzheimer disease, as well as to healthy aging and longevity. The gene variants underlying these protein isoforms, known as ε2, ε3, and ε4, are allelic forms of the APOE gene, resulting from different haplotypes at the APOE locus (19q13.31). In particular, they result from three of the four haplotypes expected by the combinations of the alleles of the two single-nucleotide polymorphisms rs429358 and rs7412. The fourth missing haplotype, known as ε3r, has been identified in only two Caucasian families from Italy and in one Yoruba family from Nigeria worldwide. Thus, this fourth APOE gene variant is rare, and it encodes a protein isoform, identified as E3r, showing identical physical characteristics to E3, that conversely, is the most common form of apoE in humans. In this review article, we report the identification of the haplotype ε3r in a third Caucasian family from Italy, and then attempt to re-examine the current knowledge regarding the APOE polymorphism, taking into account this fourth haplotype. We also focus on the commonly accepted hypothesis for the evolution of the common APOE gene variants, in which we include the ε3r haplotype, previously not considered.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Seripa, D., D'Onofrio, G., Panza, F., Cascavilla, L., Masullo, C., & Pilotto, A. (2011). The genetics of the human APOE polymorphism. Rejuvenation research. https://doi.org/10.1089/rej.2011.1169
Vancouver
Seripa D, D'Onofrio G, Panza F, Cascavilla L, Masullo C, Pilotto A. The genetics of the human APOE polymorphism. Rejuvenation research. 2011. doi:10.1089/rej.2011.1169. PMID: 21958003.
BibTeX
@article{seripa2011-21958003,
author = {Seripa, D. and D'Onofrio, G. and Panza, F. and Cascavilla, L. and Masullo, C. and Pilotto, A.},
title = {{The genetics of the human APOE polymorphism}},
journal = {Rejuvenation research},
year = {2011},
doi = {10.1089/rej.2011.1169},
pmid = {21958003},
url = {https://doi.org/10.1089/rej.2011.1169}
}
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Key findings
- In particular, they result from three of the four haplotypes expected by the combinations of the alleles of the two single-nucleotide polymorphisms rs429358 and rs7412.
Why it matters
This review describes the genetics of the APOE variants E2, E3, and E4 and reports a rare fourth variant, E3r, found in a few families. It is background genetics and does not report a treatment or cure.
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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 (Rejuvenation research) |
| Journal's citation record | 1 / 4 | Rejuvenation Research: journal h-index 85 (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 | 2011 — within 20 year(s) of the newest study here |
| 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 128 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 7.5 citations a year over 17 year(s) since 2011 |
| Impact for its field and year | 3 / 6 | Cited 3.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 2 other studies in this library |
| Still being cited | 2 / 4 | Cited 33 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Alberto Pilotto: h-index 55 (OpenAlex, whole career) |
| Institution's track record | 0 / 3 | Università Cattolica del Sacro Cuore: institution h-index 606 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 21958003) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 40 / 100 | — |
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