Abstract
This chapter discusses the dependency of basal forebrain cholinergic neurons (BFCNs) on endogenous nerve growth factor (NGF) for the structural and physiologic maintenance of the neuronal cell somata, axonal projections, and terminal synapses. It covers the discovery of NGF and the occurrence of a CNS neurotrophin family and their cognate receptors and their signaling mechanisms. It concludes with a description of the NGF metabolic pathway and its dysregulation in Alzheimer disease (AD) and Down syndrome pathology, explaining the progressive atrophy of BFCNs, which starts at preclinical stages and is reflected in body fluid biomarkers.