Topic: Amyloid, tau and blood-test diagnosis
Family history is the second strongest risk factor for Alzheimer disease (AD) following advanced age. Twin and family studies indicate that genetic factors are estimated to play a role in at least 80% of AD cases. The inheritance of AD exhibits a dichotomous pattern. On one hand, rare mutations in APP, PSEN1, and PSEN2 virtually guarantee early-onset (<60 years) familial AD, which represents ∼5% of AD. On the other hand, common gene polymorphisms, such as the ε4 and ε2 variants of the APOE gene, can influence susceptibility for ∼50% of the common late-onset AD. These four genes account for 30%-50% of the inheritability of AD. Genome-wide association studies have recently led to the identification of 11 additional AD candidate genes. This paper reviews the past, present, and future attempts to elucidate the complex and heterogeneous genetic underpinnings of AD.
Key findings
- Twin and family studies indicate that genetic factors are estimated to play a role in at least 80% of AD cases.
Why it matters
This 2012 review reports that, according to twin and family studies, genes play a role in at least 80% of Alzheimer's cases, and that family history is the strongest risk factor after age. Only rare mutations in APP, PSEN1 and PSEN2 "virtually guarantee" the disease, and they account for about 5% of cases, all early-onset (before 60), while common APOE variants influence susceptibility in about half of late-onset cases. Together these four genes explain only 30–50% of the inherited risk, and the review's count of further candidate genes reflects research as of 2012.
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Study details
- Evidence strengthLow
How this study scored 51/100
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. We have no data on impact for its field and year, so that was left out: it earned 48 of the 94 points we could judge it on, which is 51 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Cold Spring Harbor perspectives in medicine) |
| Journal's citation record | 2 / 4 | Cold Spring Harbor Perspectives in Medicine: journal h-index 197 (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 | 2012 — 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 | 6 / 7 | Cited 726 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 45.4 citations a year over 16 year(s) since 2012 |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | 4 / 6 | Cited by 36 other studies in this library |
| Still being cited | 3 / 4 | Cited 150 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Rudolph E. Tanzi: h-index 145 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 23028126) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 48 / 94 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 48 of the 94 points we could judge it on is 51 out of 100. |
| Total | 51 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1101/cshperspect.a006296
- PubMed: 23028126
- Original source →
- Free full text: PubMed Central →
Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).
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
Tanzi, R. E. (2012). The genetics of Alzheimer disease. Cold Spring Harbor perspectives in medicine. https://doi.org/10.1101/cshperspect.a006296
Vancouver
Tanzi RE. The genetics of Alzheimer disease. Cold Spring Harbor perspectives in medicine. 2012. doi:10.1101/cshperspect.a006296. PMID: 23028126.
BibTeX
@article{tanzi2012-23028126,
author = {Tanzi, R. E.},
title = {{The genetics of Alzheimer disease}},
journal = {Cold Spring Harbor perspectives in medicine},
year = {2012},
doi = {10.1101/cshperspect.a006296},
pmid = {23028126},
url = {https://doi.org/10.1101/cshperspect.a006296}
}
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