CD33 forms functional dimers on cell surface to modulate Alzheimer risk
This study reveals the critical role of CD33<sup>M</sup> in AD pathology by elucidating its molecular mechanisms. We provide direct evidence that CD33<sup>M</sup> and CD33<sup>m</sup> isoforms can form both homodimers and heterodimers. However, only CD33<sup>M</sup> isoforms are preferentially trafficked to the cell surface and form functional dimers. These findings advance our understanding of the molecular basis of CD33's immuno-inhibitory function and offer new insights into its involvement in AD risk, potentially paving the way for the development of targeted therapeutic strategies.
Authors
- Jean Sévalle
- Elizabeth M. Bradshaw (ORCID: https://orcid.org/0000-0002-6766-4325)
- Wesley B. Asher (ORCID: https://orcid.org/0000-0001-7437-218X)
- Kanayo Satoh (ORCID: https://orcid.org/0009-0000-4520-2560)
- Christopher Böhm
- P. E. Fraser
- Peter St George‐Hyslop (ORCID: https://orcid.org/0000-0003-0796-7209)
- Jonathan A. Javitch (ORCID: https://orcid.org/0000-0001-7395-2967)
- Jamie J. Manning (ORCID: https://orcid.org/0000-0002-6945-2254)
- Masahiro Enomoto (ORCID: https://orcid.org/0000-0002-9411-2999)
- Roger B. Dodd (ORCID: https://orcid.org/0000-0003-4268-1863)
- Deniz Ghaffari
- Mamunur Rashid (ORCID: https://orcid.org/0000-0001-6768-1814)
- Beatrice Acheson
- George V. Dukas
- Seema Qamar (ORCID: https://orcid.org/0009-0002-6011-5785)
- Ye Zhou
- Yalun Zhang
- Jennifer K Griffin
- Fusheng Chen
Institutions
- University Health Network (CA)
- University of Toronto (CA)
- University of Cambridge (GB)
- Bridge University (SS)
- Columbia University (US)
Publication Details
- Journal
- Alzheimer s & Dementia
- Published
- 2025-12-01
- DOI
- https://doi.org/10.1002/alz70855_101544
- Primary Topic
- Alzheimer's disease research and treatments
- Type
- article
- Field-Weighted Citation Impact
- 0.00