In light of these collective data, one model, which may reconcile the opposing trends in the effects of PLCG2 and ABI3 variants in AD vs. PSP and MSA in our study is that activation of innate immunity relatively early in the neurodegenerative process may be beneficial, especially in the context of extracellular Aß pathology. The gene discussed is PLCG2; the disease is multiple system atrophy.