Similarly, reductions inpathway effectors were also observed.14,15 These eventsare often paralleled by increased PDE activity in cerebrovessels,putamen, and temporal cortex (especially PDE5).16,17 However, AD-associated alterations in expression/activity are stilldebated, with contrasting data being reported and doubts about thecause–effect relationship between the events. This evidence concerns the gene PDE5A and Alzheimer disease.