2- The authors may need to clarify the mechanism of ABCA1-dependent APOE uptake in microglia. As a whole, they hypothesized that ABCA1-mediated APOE uptake causes increased A production, leading to further A-induced neurotoxicity. But it is not clear why the authors suggest that ABCA1-mediated APOE uptake is the main determinant of A neurotoxicity.
The current study also assessed the effect of age on the association between RABV infection and brain pathology, especially neuroinflammation. The data showed that the number of RABV-infected neurons in the brain was negatively correlated with age. The presence of APOE4 did not alter the correlation between age and RABV infection, indicating that age-related disease progression and the pathology of RABV encephalitis is similar in older and younger individuals. Overall, the data indicated that not only APOE4 but also age-related factors contribute to the neurotropic potential of RABV and disease severity.
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