Finally, if the disease-relevant insult due to astrocytic tau internalization is secondary to the spread of tau pathology, such as BBB damage, pro-inflammatory cytokine cascades, or metabolic dysfunction, such evidence would further support the vascular, inflammatory, and metabolic hypotheses of AD, respectively, and further investigation of these downstream effects could serve to identify targets in those domains. The gene discussed is MAPT; the disease is Alzheimer disease.