Increased proNGF levels in subjects with mild cognitive impairment and mild Alzheimer disease

Document Type

Article

Abstract

Nerve growth factor (NGF) is critical for the regulation, differentiation, and survival of basal forebrain cholinergic neurons that degenerate in the late stage of Alzheimer disease (AD). The precursor of NGF (proNGF) is the predominant form of NGF in brain and is increased in end stage AD. To determine whether this increase in proNGF is an early or late change during the progression of cognitive decline, we used Western blotting to measure the relative amounts of proNGF protein in the parietal cortex from subjects clinically classified with no cognitive impairment (NCI; n = 20), mild cognitive impairment (MCI; n = 20), or mild to moderate AD (n = 19). We found that proNGF increased during the prodromal stage of AD. The amount of proNGF protein was 1.4-fold greater in the MCI group as compared to NCI, and was 1.6-fold greater in mild-moderate AD as compared to NCI, similar to our previous findings of a 2-fold increase in end stage AD. There was a negative correlation between proNGF levels and Mini Mental Status Examination (MMSE) score, demonstrating that the accumulation of proNGF is correlated with loss of cognitive function. These findings demonstrate that proNGF levels increase during the preclinical stage of AD and may reflect an early biological marker for the onset of AD.

Keywords

Alzheimer disease, Cholinergic, Nerve growth factor (NGF), Neurodegeneration, Neurotrophic factor, Parietal cortex, Western blotting

Publication Date

1-1-2004

Publication Title

Journal of Neuropathology and Experimental Neurology

ISSN

00223069

Volume

63

Issue

6

First Page

641

Last Page

649

PubMed ID

15217092

Digital Object Identifier (DOI)

10.1093/jnen/63.6.641

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