Detection of NGF-like activity in human brain tissue: increased levels in Alzheimer's disease

Abstract

A two-site ELISA and a bioassay were used to detect NGF-like activity in human brain tissue. Both assays detected mouse NGF and recombinant human NGF with approximately equal sensitivity, whereas the antibodies showed little cross-reactivity with the recombinant human proteins NT-3 and brain-derived neurotrophic factor. NGF-like activity was detected in fresh human cortical samples obtained from epileptic patients, with the highest activity observed in the right hemisphere of men. NGF-like activity was subsequently measured in autopsy samples of frontal and occipital cortex from patients with Alzheimer's disease (AD) and from individuals with no history or pathological evidence of AD. Based on both the ELISA and the bioassay measurements, NGF-like activity was significantly elevated in both brain regions in AD. These results demonstrate the feasibility of detecting NGF-like activity in both fresh and postmortem human brain tissue and further suggest that AD is characterized by increased, rather than decreased, levels of cortical beta-NGF. The AD-related increase in NGF may be a consequence of degenerative changes in the basal forebrain cholinergic system.

TrkA‐immunoreactive profiles in the central nervous system: Colocalization with neurons containing p75 nerve growth factor receptor, choline acetyltransferase, and serotonin

“…Preliminary investigations in our laboratory using an antibody which recognizes endogenous NGF have revealed a reduction in NGF-like immunoreactivity within remaining basal fore-brain neurons in AD (Mufson et al, 1993b. In AD, NGF levels in basal forebrain target regions have been reported to remain unchanged (Goedert et al, 1986) or increased (Crutcher et al, 1993) in cortex. Similarly, levels of the low-affinity p75 NGF receptor has been discribed as either stable or elevated in AD (Higgins and Mufson, 1989;Ernfors et al, 1990a,b).…”

Nerve growth factor as a paradigm of neurotrophins related to Alzheimer's disease

“…choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) with a decrease of cholinergic transmission (Svendsen et al, 1991;Venero et al, 1994). In contrast, the levels of proNGF, a precursor of NGF, which is the predominant form in human and rodent brain, are doubled in frontal and occipital cortex and in hippocampus in late-stage AD (Crutcher et al, 1993;Scott et al, 1995;Narisawa-Saito et al, 1996;Hellweg et al, 1998;Hock et al, 2000;Fahnestock et al, 2001;Peng et al, 2004) and appear to be 40%-50% increased in individuals with mild cognitive impairment (MCI) (Peng et al, 2004), suggesting that an unbalance in NGF processing may contribute, and in some instances cause, the onset of AD neurodegeneration. In this regard, an unbalance of the cascade of protease complex (plasminogen/plasmin; tPA,Neuroserpin, MMP-9) leading to a deficit of proNGF/NGF has been recently reported in human AD brains (Bruno et al, 2006;Cuello and Bruno, 2007).…”

Expressions of Axl and Tyro-3 receptors are under regulation of nerve growth factor and are involved in differentiation of PC12 cells

“…Although accumulative lines of evidence illustrate that insufficiency of NGF plays an important role in the process of cholinergic neuronal loss and degeneration and is a main event of the neurodegenerative diseases such as AD, there are some studies demonstrating that NGF level is increased in the brain of AD patients [14][15][16][17] . These findings suggest that there is dysfunction of receptors in aging brain.…”