Cholinergic Systems in Aging and Alzheimer’s Disease: Neurotrophic Molecular Analysis

Alzheimer’s disease (AD) is characterized by a progressive phenotypic downregulation of markers within the cholinergic basal forebrain (CBF) system including CBF cell loss and reduced cortical choline acetyltransferase activity associated with cognitive decline. Growing evidence suggests that imbalances in the expression of nerve growth factor (NGF), its precursor proNGF and the tyrosine kinase A (TrkA) high-affinity and p75NTR low-affinity NGF receptors, as well as metalloproteinase are key factors underlying CBF dysfunction at the onset of AD. This article discusses shifts in the balance of the proNGF:NGF receptor:metalloproteinase system during aging and the progression of AD.