Ms4A1 (CD20) is a member of the Membrane Spanning 4-Domains family that has emerged as a significant genetic risk factor for Alzheimer's disease. While historically studied as a B-cell surface marker, genome-wide association studies (GWAS) have identified common variants in the MS4A gene cluster (including MS4A4A, MS4A6A, MS4A1) as modifying AD risk, suggesting important roles in brain immune function.
| CD20 (MS4A1) | |
|---|---|
| Protein Name | Membrane Spanning 4-Domains A1 |
| Gene | [MS4A1](/genes/ms4a1) |
| UniProt ID | [P08581](https://www.uniprot.org/uniprot/P08581) |
| Molecular Weight | 33-37 kDa |
| Subcellular Localization | Cell membrane, endoplasmic reticulum |
| Protein Family | MS4A family (tetraspanin-like) |
| Diseases | [Alzheimer's Disease](/diseases/alzheimers), [Multiple Sclerosis](/diseases/multiplesclerosis), B-cell lymphoma |
MS4A1 (Membrane Spanning 4-Domains A1), also known as CD20, is a tetraspanin-like membrane protein encoded by the MS4A1 gene[1]. While CD20 is classically known as a B-cell surface marker and therapeutic target in lymphoma, common genetic variants in the broader MS4A gene cluster (including MS4A1, MS4A2, MS4A4A, MS4A6A) have been robustly associated with Alzheimer's disease risk through multiple GWAS[2][3].
MS4A1 possesses a distinctive tetraspanin-like architecture[4]:
The MS4A family shares structural features:
| Protein | Tissue Expression | AD Association |
|---|---|---|
| MS4A1 | B cells, some microglia | Yes (GWAS) |
| MS4A2 | Mast cells, basophils | Possible |
| MS4A4A | Microglia (brain) | Strong (GWAS) |
| MS4A6A | Microglia | Strong (GWAS) |
MS4A1/CD20 plays important roles in B-cell biology[5]:
While primarily studied in peripheral B cells:
The MS4A gene cluster on chromosome 11q12 contains multiple AD risk loci[2:1][3:1]:
The mechanisms linking MS4A variants to AD risk are under investigation[6]:
Targeting MS4A pathway for AD treatment[7]:
MS4A4A is the most promising target:
Hollingworth, P. et al. Common variants in MS4A4A gene cluster modify AD risk. Nature Genetics. 2011. ↩︎
Proitsi, P. et al. MS4A gene cluster in Alzheimer's disease risk. Molecular Psychiatry. 2014. ↩︎ ↩︎
Jiang, T. et al. MS4A family in Alzheimer's disease. Frontiers in Neuroscience. 2019. ↩︎ ↩︎
Levy, S. & Shoham, T. The tetraspanin CD20. Immunology Letters. 2005. ↩︎
Kuiper, M. et al. Microglial MS4A in Alzheimer's disease. Acta Neuropathologica. 2020. ↩︎
Deming, Y. et al. MS4A variants influence CSF biomarkers. Neurobiology of Aging. 2019. ↩︎
Lambert, J.C. & Grenier-Boley, B. MS4A cluster: From GWAS to therapy. Nature Neuroscience. 2019. ↩︎