It is notable that the neurotoxicity of intracellular tau aggregates (NFT) on neuronal survival remains somewhat controversial.62,63 Pathologic tau aggregation associated with cellular senescence has been reported in human AD and rodent models preceding neurodegeneration.42,64,65 The expression of p16INK4a was also observed in cells bearing tauopathy within BF of AD mice in our study (Fig. 7C and F). Here, CDKN2A is linked to Alzheimer disease.