MAPT and Alzheimer disease: One of the earliest tau pathology changes in Alzheimer's disease is observed in the CSF p-tau that reflects hyperphosphorylated tau in its soluble form and is closely associated with Aβ, precedes the development of intracellular neurofibrillary tau aggregates.36,45 Consequently, further investigations are necessary to comprehensively examine the effect of microglia on hyperphosphorylation and aggregation of p-tau.