MAPT and Alzheimer disease: Considering this, we conjecture that mild decreased CX3CL1-CX3CR1 due to intraneuronal Aβ accumulation in the early stage of AD increases clearance of Aβ deposition by enhancing the phagocytosis of microglia while resulting in tau hyperphosphorylation and severe downgraded CX3CL1-CX3CR1 signal gives rise to deregulated microglia and abnormally excited neuron which lead to neuron damage and loss in the progression of AD.