DAP12 deletion reduces neuronal SLIT2 and demyelination and enhances brain resilience in female tauopathy mice
Our study identifies a novel DAP12-dependent mechanistic link between upregulated Slit2 expression in excitatory neurons and oligodendrocyte-dependent myelination loss in tauopathy. Despite elevating tau load, the absence of microglial Dap12 ameliorates neuroinflammation and improves brain functions in tauopathy mice. Our study suggests that selectively targeting the toxic aspects of DAP12 signaling while preserving its beneficial functions may be a promising strategy to enhance brain resilience in AD.
Authors
- Man Ying Wong (ORCID: https://orcid.org/0000-0002-2165-9328)
- Hongjun Fu (ORCID: https://orcid.org/0000-0001-5346-7075)
- Qin Ma (ORCID: https://orcid.org/0000-0002-3264-8392)
- Tark Patel
- Chloe Lopez-Lee (ORCID: https://orcid.org/0000-0002-1013-3005)
- Yige Huang (ORCID: https://orcid.org/0000-0002-4925-7865)
- Gillian Carling (ORCID: https://orcid.org/0000-0002-1504-1716)
- Sadaf Amin (ORCID: https://orcid.org/0000-0002-3758-6485)
- Shiaoching Gong (ORCID: https://orcid.org/0000-0002-5907-5539)
- Wenjie Luo (ORCID: https://orcid.org/0000-0003-3752-8266)
- Sue‐Ann Mok (ORCID: https://orcid.org/0000-0003-4593-3368)
- Bangyan Liu
- Li Gan (ORCID: https://orcid.org/0000-0003-4600-275X)
- Li Fan (ORCID: https://orcid.org/0000-0003-1780-6919)
- Nessa Foxe
- Aviram Nessim
- Bin Zhang (ORCID: https://orcid.org/0000-0002-9549-5653)
- Qi Guo (ORCID: https://orcid.org/0000-0002-2367-8389)
- Winston Wang (ORCID: https://orcid.org/0000-0003-4442-174X)
- Hao Chen (ORCID: https://orcid.org/0000-0002-9179-5720)
- Jingjie Zhu (ORCID: https://orcid.org/0000-0001-8169-4873)
- Won-Min Song
Institutions
- University of Alberta (CA)
- Cornell University (US)
- MIND Research Institute (US)
- Weill Cornell Medicine (US)
- The Ohio State University (US)
- Icahn School of Medicine at Mount Sinai (US)
Publication Details
- Journal
- Molecular Neurodegeneration
- Published
- 2025-12-02
- DOI
- https://doi.org/10.1186/s13024-025-00903-3
- Primary Topic
- Axon Guidance and Neuronal Signaling
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Ohio State University
- National Institutes of Health
- Weill Cornell Medical College