title: Nerve growth factor and Alzheimer's disease: new facts for an old hypothesis.
abstract: Understanding sporadic Alzheimer's disease (AD) onset and progression requires an explanation of what triggers the common core of abnormal processing of the amyloid precursor protein and tau processing. In the quest for upstream drivers of sporadic, late-onset AD neurodegeneration, nerve growth factor (NGF) has a central role. Initially connected to AD on a purely correlative basis, because of its neurotrophic actions on basal forebrain cholinergic neurons, two independent lines of research, reviewed in this article, place alterations of NGF processing and signaling at the center stage of a new mechanism, leading to the activation of amyloidogenesis and tau processing. Thus, experimental studies on NGF deficit induced neurodegeneration in transgenic mice, as well as the mechanistic studies on the anti-amyloidogenic actions of NGF/TrkA signaling in primary neuronal cultures demonstrated a novel causal link between neurotrophic signaling deficits and Alzheimer's neurodegeneration. Around these results, a new NGF hypothesis can be built, with neurotrophic deficits of various types representing an upstream driver of the core AD triad pathology. According to the new NGF hypothesis for AD, therapies aimed at reestablishing a correct homeostatic balance between ligands (and receptors) of the NGF pathway appear to have a clear and strong rationale, not just as long-term cholinergic neuroprotection, but also as a truly disease-modifying approach.
authors.affiliation: European Brain Research Institute Rita Levi-Montalcini, Via del Fosso di Fiorano 64/65, 00143 Rome, Italy. a.cattaneo@ebri.it
authors.forename: Antonino
authors.initials: A
authors.lastname: Cattaneo
authors.forename: Pietro
authors.initials: P
authors.lastname: Calissano
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D004195:Disease Models, Animal; D008954:Models, Biological; D020932:Nerve Growth Factor / Q000378:metabolism*; D013569:Synapses / Q000473:pathology
chemical_list: D016229:Amyloid beta-Peptides; D020932:Nerve Growth Factor