Dementia: genes and variants
Dementia is linked to 7 analyzed proteins (PSEN1, APOE, APP, GRIN2A, GRIN2B, GRN and PRNP). 2 DNA variants are known to cause it; 2 more are uncertain, and 0 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Genes linked to Dementia
PSEN1: Presenilin-1
Its catalytic activity within gamma-secretase cleaves APP and many other membrane proteins, including Notch receptors. Pathogenic variants alter amyloid-beta production and are the most common known cause of autosomal dominant early-onset Alzheimer disease.
2 disease-causing and 0 uncertain variants in PSEN1 are linked to Dementia.
APOE: Apolipoprotein E
It redistributes cholesterol and other lipids between tissues by directing remnant lipoproteins to LDL-receptor-family members. The common epsilon4 isoform strongly increases late-onset Alzheimer disease risk and also influences plasma lipids and cardiovascular risk.
0 disease-causing and 0 uncertain variants in APOE are linked to Dementia.
APP: Amyloid-beta precursor protein
Its processing produces multiple fragments involved in neuronal biology, including amyloid-beta peptides generated by beta- and gamma-secretase cleavage. Increased amyloidogenic processing, pathogenic variants, or increased gene dosage can cause autosomal dominant Alzheimer disease or cerebral amyloid angiopathy.
0 disease-causing and 0 uncertain variants in APP are linked to Dementia.
GRIN2A: Glutamate receptor ionotropic, NMDA 2A
It helps determine the kinetics and signaling properties of NMDA receptors, particularly in cortical circuits involved in language and epilepsy. Pathogenic variants cause a spectrum of developmental epileptic encephalopathies and epilepsy-aphasia disorders.
0 disease-causing and 0 uncertain variants in GRIN2A are linked to Dementia.
GRIN2B: Glutamate receptor ionotropic, NMDA 2B
It confers distinct developmental and signaling properties on NMDA receptors and is highly expressed during early brain development. De novo pathogenic variants can cause intellectual disability, developmental delay, epilepsy, abnormal movements, and autism-related phenotypes.
0 disease-causing and 0 uncertain variants in GRIN2B are linked to Dementia.
GRN: Progranulin
It is secreted and proteolytically processed into granulins and has roles in lysosomal function, inflammation, neuronal survival, and tissue repair. Heterozygous loss-of-function variants cause frontotemporal dementia through progranulin haploinsufficiency, while biallelic loss causes neuronal ceroid lipofuscinosis.
0 disease-causing and 0 uncertain variants in GRN are linked to Dementia.
PRNP: Major prion protein
Its normal cellular form is enriched in the nervous system, but misfolding into self-propagating conformations can template further protein conversion. This process causes prion diseases, while germline pathogenic variants underlie inherited Creutzfeldt-Jakob disease, Gerstmann-Straussler-Scheinker disease, and fatal familial insomnia.
0 disease-causing and 0 uncertain variants in PRNP are linked to Dementia.
Weakly linked (only a few uncertain records): APOA5 and MRE11.
Known disease-causing variants in Dementia
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| PSEN1 F105C | 105 | Lumenal | Disease-causing (★) |
| PSEN1 F237L | 237 | Transmembrane | Disease-causing (★) |
Same protein, different disease
- Alzheimer disease is also caused by PSEN1 variants; they fall mostly in different places as the Dementia variants (88 disease-causing).
- Frontotemporal dementia is also caused by PSEN1 variants; they fall mostly in different places as the Dementia variants (63 disease-causing).
- Acne inversa, familial, 3 is also caused by PSEN1 variants; they fall mostly in different places as the Dementia variants (57 disease-causing).
- Pick disease is also caused by PSEN1 variants; they fall mostly in different places as the Dementia variants (26 disease-causing).
Diseases related to Dementia
- Alzheimer disease, also linked to APOE, APP, GRIN2A, GRIN2B and 2 more
- Frontotemporal dementia, also linked to GRN and PSEN1
- Epilepsy, also linked to GRIN2A and GRIN2B
- Early-onset autosomal dominant Alzheimer disease, also linked to APOE and PSEN1
- Parkinson disease, also linked to GRIN2A and GRIN2B
- Familial hypercholesterolemia, also linked to APOE
- Telangiectasia, hereditary hemorrhagic, type 2, also linked to PSEN1
- Dilated cardiomyopathy, also linked to PSEN1
- Landau-Kleffner syndrome, also linked to GRIN2A
- Acne inversa, familial, 3, also linked to PSEN1
- Type 2 diabetes mellitus, also linked to APOE
- Age related macular degeneration 9, also linked to APOE
Frequently asked questions
Which genes are linked to Dementia?
In CATVariant, Dementia is linked to 7 analyzed proteins: PSEN1 (Presenilin-1), APOE (Apolipoprotein E), APP (Amyloid-beta precursor protein), GRIN2A (Glutamate receptor ionotropic, NMDA 2A), GRIN2B (Glutamate receptor ionotropic, NMDA 2B), GRN (Progranulin) and 1 more.
How many genetic variants are linked to Dementia?
5 variants: 2 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 2 are of uncertain significance or have conflicting reports.
Which uncertain variants in Dementia look disease-causing?
None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.
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