脑脊液神经生长因子前体：早期阿尔茨海默病的假定的生物标志物

Title:Cerebrospinal Fluid proNGF: A Putative Biomarker for Early Alzheimer’s Disease

Volume: 13 Issue: 7

Author(s): Scott E. Counts, Bin He, John G. Prout, Bernadeta Michalski, Lucia Farotti, Margaret Fahnestock, Elliott J. Mufson

Affiliation:

关键词: 阿尔茨海默病，淀粉样蛋白，生物标志物，脑脊液，轻度认知功能障碍，神经生长因子前体，tau蛋白。

摘要: The discovery of biomarkers for the onset of Alzheimer’s disease (AD) is essential for disease modification strategies. To date, AD biomarker studies have focused on brain imaging and cerebrospinal fluid (CSF) changes in amyloid- β (Aβ) peptide and tau proteins. While reliable to an extent, this panel could be improved by the inclusion of novel biomarkers that optimize sensitivity and specificity. In this study, we determined whether CSF levels of the nerve growth factor (NGF) precursor protein, proNGF, increased during the progression of AD, mirroring its up regulation in postmortem brain samples of people who died with a clinical diagnosis of mild cognitive impairment (MCI) or AD. Immunoblot analysis was performed on ventricular CSF harvested from participants in the Rush Religious Orders Study with an antemortem clinical diagnosis of no cognitive impairment (NCI), amnestic MCI (aMCI, a putative prodromal AD stage), or mild/moderate AD. ProNGF levels were increased 55% in aMCI and 70% in AD compared to NCI. Increasing CSF proNGF levels correlated with impairment on cognitive test scores. In a complementary study, we found that proNGF was significantly increased by 30% in lumbar CSF samples derived from patients with a clinical dementia rating (CDR) of 0.5 or 1 compared to those with a CDR = 0. Notably, proNGF/Aβ1-42 levels were 50% higher in CDR 0.5 and CDR 1 compared to CDR 0 controls. By contrast, ELISA measurements of CSF brain-derived neurotrophic factor (BDNF) did not distinguish aMCI from NCI. Taken together, these results suggest that proNGF protein levels may augment the diagnostic accuracy of currently used CSF biomarker panels.

Cite this article as:

Scott E. Counts, Bin He, John G. Prout, Bernadeta Michalski, Lucia Farotti, Margaret Fahnestock, Elliott J. Mufson , Cerebrospinal Fluid proNGF: A Putative Biomarker for Early Alzheimer’s Disease, Current Alzheimer Research 2016; 13 (7) . https://dx.doi.org/10.2174/1567205013666160129095649