title: Impairment of the nerve growth factor pathway driving amyloid accumulation in cholinergic neurons: the incipit of the Alzheimer's disease story?
abstract: The current idea behind brain pathology is that disease is initiated by mild disturbances of common physiological processes. Overtime, the disruption of the neuronal homeostasis will determine irreversible degeneration and neuronal apoptosis. This could be also true in the case of nerve growth factor (NGF) alterations in sporadic Alzheimer's disease (AD), an age-related pathology characterized by cholinergic loss, amyloid plaques and neurofibrillary tangles. In fact, the pathway activated by NGF, a key neurotrophin for the metabolism of basal forebrain cholinergic neurons (BFCN), is one of the first homeostatic systems affected in prodromal AD. NGF signaling dysfunctions have been thought for decades to occur in AD late stages, as a mere consequence of amyloid-driven disruption of the retrograde axonal transport of neurotrophins to BFCN. Nowadays, a wealth of knowledge is potentially opening a new scenario: NGF signaling impairment occurs at the onset of AD and correlates better than amyloid load with cognitive decline. The recent acceleration in the characterization of anatomical, functional and molecular profiles of early AD is aimed at maximizing the efficacy of existing treatments and setting novel therapies. Accordingly, the elucidation of the molecular events underlying APP metabolism regulation by the NGF pathway in the septo-hippocampal system is crucial for the identification of new target molecules to slow and eventually halt mild cognitive impairment (MCI) and its progression toward AD.
authors.affiliation: European Brain Research Institute (EBRI)/R.L. Montalcini Foundation, and Institute of Cell Biology and Neuroscience, National Research Council (IBCN-CNR), Rome, Italy.
authors.forename: Viviana
authors.initials: V
authors.lastname: Triaca
authors.affiliation: European Brain Research Institute (EBRI)/R.L. Montalcini Foundation, and Institute of Cell Biology and Neuroscience, National Research Council (IBCN-CNR), Rome, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Calissano
keywords: Alzheimer's disease onset; NGF pathway disturbances; basal forebrain cholinergic neurons; intraneuronal amyloid generation and release