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

Shiyong Peng, Joanne Wuu, Elliott J. Mufson, Margaret Fahnestock

Research output: Contribution to journalArticlepeer-review

185 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)641-649
Number of pages9
JournalJournal of neuropathology and experimental neurology
Volume63
Issue number6
DOIs
StatePublished - Jun 2004
Externally publishedYes

Keywords

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

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neuroscience(all)

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