How DAP12 deletion enhances brain resilience in female tauopathy mice

Microglia selectively expresses DAP12 (DNAX-activation protein 12), which, plays a crucial role in microglial immune responses.

Previously, it was show that tauopathy mice lacking DAP12 exhibit higher tau pathology but are protected from tau pathology-induced cognitive deficits but the mechanism remains elusive.

The authors in this study show that  tau processing in primary microglia is reduced by Dap12 deletion, while, tau pathology increased in female tauopathy mice, with minimal effects on males. However, brain inflammation, synapse loss, and demyelination are reduced by Dap12 deletion indicating enhanced resilience to tau toxicity.

The authors also show that elevated SLIT2 levels and demyelination in tauopathy and  is reversed by Dap12 deletion. The author s also found correlation of SLIT2 expression and tau pathology in AD brain tissue.

https://link.springer.com/article/10.1186/s13024-025-00903-3

https://sciencemission.com/DAP12-deletion-reduces-neuronal-SLIT2