A New Look at Alzheimer's: The P-Tau Cascade as the Basis for Acetylcholinesterase Inhibitor-induced Anti-neurodegeneration

Abstract

The pathophysiological cascade triggered by hyperphosphorylated tau protein (P-tau) provides a unifying framework for the nerve growth factor (NGF) deficit, basal forebrain neurodegeneration, loss of cortical and hippocampal acetylcholine, and resulting dementia that is observed in Alzheimer's disease [1] (Figure 1). The P-tau cascade, including the involvement of NGF, also provides a rational mechanism by which acetylcholinesterase (AChE) inhibitors may produce their heretofore poorly understood anti-neurodegenerative benefits in AD [1] (Figure 2).