The cause for the neurofibrillary tangles and plaques in Alzheimer disease 
likely relates to an abnormal accumulation of their key components, which 
include β-amyloid and hyperphosphorylated tau protein. We segregated Alzheimer 
brain sections from people with end-stage disease into those with abundant 
hyperphosphorylated tau protein and those without and compared each to normal 
brains for global microRNA patterns. A significant reduced expression of several 
microRNAs, including miR-512, was evident in the Alzheimer brain sections with 
abundant hyperphosphorylated tau. Immunohistochemistry documented that 2 known 
targets of microRNA-512, cFLIP and MCL1, were significantly over expressed and 
each colocalized to neurons with the abnormal tau protein. Analysis for 
apoptosis including activated caspase-3, increased caspase-4 and caspase-8, 
apoptosis initiating factor, APAF-1 activity, and the TUNEL assay was negative 
in the areas where neurons showed hyperphosphorylated tau. MCM2 expression, a 
marker of neuroprogenitor cells, was significantly reduced in the Alzheimer 
sections that contained the hyperphosphorylated tau. These results suggest that 
a basic defect in Alzheimer disease may be the reduced microRNA-driven increased 
expression of proteins that may alter the apoptotic/antiapoptotic balance of 
neurons. This, in turn, could lead to the accumulation of key Alzheimer proteins 
such as hyperphosphorylated tau that ultimately prevent normal neuronal function 
and lead to disease symptomatology.