Alzheimer genetics comes in three tiers that behave nothing alike: rare changes that nearly decide the outcome, one common variant that matters a great deal, and a long tail that each move risk a little. This catalogue holds the second and part of the third, and none of the first — and several of the famous genes are here under completely different headings.
Solid lines are connections this site curates. Dashed lines mean the two ends share a research paper — worth knowing, and not a claim that one explains the other.
Almost everything confusing about the genetics of Alzheimer's disease comes from treating it as one thing. It is three, and they behave nothing alike.
More than 200 highly penetrant pathogenic variants in three genes — APP, PSEN1 and PSEN2 — cause a subset of early-onset familial Alzheimer's disease. Carrying one is close to determinative, and the disease usually begins well before the age most people associate with it.
This site holds none of them, and could not. They are rare, they are found by sequencing affected families, and everything in this catalogue comes from studies that scan for common differences between large groups of people. A method built to find what many people share cannot see what a few families carry. If early-onset dementia runs in your family, that is a conversation with a genetic counsellor, not a page to read.
APOE is the strongest common genetic influence on late-onset Alzheimer's disease, large enough that it is worth its own page. That page is here, including what the e2, e3 and e4 forms do and why a genotype is a probability rather than a verdict.
Beyond APOE, more than two dozen further genes have been associated with late-onset disease, each shifting risk slightly. A 2011 consortium study named MS4A4/MS4A6E, CD2AP, CD33 and EPHA1, and confirmed earlier findings at CR1, CLU and BIN1.
The heritability of Alzheimer's disease is estimated to be as high as 80%. Add up every tier above and a large share of that is still unaccounted for.
Under an Alzheimer trait, this site holds rs2075650 in APOE, rs7561528 in BIN1, rs115550680 in ABCA7, rs9349407 in CD2AP, rs10498633 in SLC24A4 and rs6857 in the PVRL2 region.
Now the part that says what a catalogue is. Several genes famous for Alzheimer's disease are in this site, filed under something else entirely:
| Gene | Known for | What it is filed under here |
|---|---|---|
| CLU | a replicated late-onset Alzheimer locus | Schizophrenia |
| SORL1 | amyloid precursor sorting | Atrial fibrillation |
| MS4A4E | the MS4A Alzheimer cluster | Lipoprotein-associated phospholipase A2 |
| MS4A6A | the same cluster | Fibrinogen |
| TOMM40 | sits beside APOE | C-reactive protein |
They are not under Alzheimer's because the position this catalogue happens to hold in each of them was reported by a study asking a different question. A gene is not a disease, and a catalogue records what was measured rather than what a gene is known for.
APP, PSEN1, PSEN2, CR1, PICALM, CD33 and TREM2 are not in this catalogue at all, under any heading.
Read this before the list. Fourteen of the variants linked to this page share one trait string, "Alzheimer disease and age of onset", and one source: a family-based analysis of roughly 3,500 people from 1,070 families. They are not that study's headline findings — its genome-wide significant results were at OSBPL6, PTPRG and PDCL3, and none of the fourteen is any of those. They are the tail of one analysis, they are rare, and they should be read as leads rather than as established Alzheimer genes. They are listed because the catalogue records what was published, and hidden results are worse than qualified ones.
It cannot diagnose. Alzheimer's disease is diagnosed clinically, with cognitive assessment, imaging and increasingly with biomarkers. No variant on this page appears in that process.
It cannot predict. Even APOE, the largest common effect known, shifts a probability. Most people carrying the higher-risk form never develop Alzheimer's disease, and most people who develop it do not carry it.
It cannot rule anything out. The variants that come closest to deciding an outcome — the ones in APP, PSEN1 and PSEN2 — are precisely the ones a common-variant catalogue does not carry. Absence from this page is a fact about the method, not about a person.
Predictive genetic information about dementia is different from most of what is on this site, because there is no treatment that changes what the result means. People who learn a result like this cannot unlearn it, and the decision about whether to look is a real one that clinical genetics services take seriously and handle with counselling before and after.
Nothing on this page is a test result, and it is not a substitute for that conversation. If Alzheimer's disease runs in your family, the useful next step is a doctor or a genetic counsellor.
What a 23andMe/AncestryDNA export or raw VCF can and can't tell you about Alzheimer's Disease comes down to these specific, well-studied positions — not a diagnosis.
IL6R · rs61812598
See detailed info →PVRL2 · rs6857
See detailed info →Databases, guidelines and references
No. Alzheimer's disease is diagnosed clinically, and no variant here appears in that process. Even APOE, the largest common genetic influence known, shifts a probability: most people carrying the higher-risk form never develop the disease, and most people who develop it do not carry it.
Because a common-variant catalogue cannot see them. More than 200 pathogenic variants in those three genes cause early-onset familial Alzheimer's disease, and they are rare changes found by sequencing affected families rather than by scanning for common differences between large groups. Their absence here says something about the method, not about any person.
Because a catalogue records what was measured, not what a gene is famous for. The position this site happens to hold in each of those genes was reported by a study asking a different question. A gene is not a disease, and the same gene turns up under whichever heading somebody happened to study it.
Not all of them. Fourteen come from one family-based analysis of about 3,500 people, and they are not that study's headline findings — its genome-wide significant results were at other genes entirely. They are listed as published leads, labelled as such, because hiding a qualified result is worse than qualifying it.
Talk to a doctor or a genetic counsellor rather than to a website. Predictive information about dementia is unusual in that no treatment changes what a result means, and it cannot be unlearned, which is why clinical genetics services offer counselling before and after testing.
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