PMID- 26825093
OWN - NLM
STAT- MEDLINE
DCOM- 20170927
LR  - 20191027
IS  - 1875-5828 (Electronic)
IS  - 1567-2050 (Print)
IS  - 1567-2050 (Linking)
VI  - 13
IP  - 7
DP  - 2016
TI  - Cerebrospinal Fluid proNGF: A Putative Biomarker for Early Alzheimer's Disease.
PG  - 800-8
AB  - 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- beta (Abeta) 
      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/Abeta1-42 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.
FAU - Counts, Scott E
AU  - Counts SE
AD  - Michigan State University, 333 Bostwick Ave NE, Grand Rapids, MI 49503, USA. 
      scott.counts@hc.msu.edu.
FAU - He, Bin
AU  - He B
FAU - Prout, John G
AU  - Prout JG
FAU - Michalski, Bernadeta
AU  - Michalski B
FAU - Farotti, Lucia
AU  - Farotti L
FAU - Fahnestock, Margaret
AU  - Fahnestock M
FAU - Mufson, Elliott J
AU  - Mufson EJ
AD  - Barrow Neurological Institute, 350 W. Thomas St., Phoenix, AZ 85013, 
      602-406-8525, USA. elliott.mufson@dignityhealth.org.
LA  - eng
GR  - P30 AG053760/AG/NIA NIH HHS/United States
GR  - R21 AG042146/AG/NIA NIH HHS/United States
GR  - R01 AG043375/AG/NIA NIH HHS/United States
GR  - P50 AG005136/AG/NIA NIH HHS/United States
GR  - CIHR/Canada
GR  - P30 AG010161/AG/NIA NIH HHS/United States
GR  - P01 AG014449/AG/NIA NIH HHS/United States
GR  - R21 AG026032/AG/NIA NIH HHS/United States
GR  - R21 AG053581/AG/NIA NIH HHS/United States
GR  - P30 AG019610/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United Arab Emirates
TA  - Curr Alzheimer Res
JT  - Current Alzheimer research
JID - 101208441
RN  - 0 (Biomarkers)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Protein Precursors)
RN  - 0 (pro-nerve growth factor, human)
RN  - 9061-61-4 (Nerve Growth Factor)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Alzheimer Disease/*cerebrospinal fluid
MH  - Analysis of Variance
MH  - Biomarkers/*cerebrospinal fluid
MH  - Brain-Derived Neurotrophic Factor/cerebrospinal fluid
MH  - Cognitive Dysfunction/cerebrospinal fluid
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Humans
MH  - Male
MH  - Mental Status Schedule
MH  - Middle Aged
MH  - Nerve Growth Factor/*cerebrospinal fluid
MH  - Protein Precursors/*cerebrospinal fluid
PMC - PMC5827942
MID - NIHMS944066
COIS- CONFLICT OF INTEREST The authors confirm that this article content has no 
      conflict of interest.
EDAT- 2016/01/31 06:00
MHDA- 2017/09/28 06:00
PMCR- 2018/02/27
CRDT- 2016/01/31 06:00
PHST- 2015/10/19 00:00 [received]
PHST- 2015/12/08 00:00 [revised]
PHST- 2015/12/10 00:00 [accepted]
PHST- 2016/01/31 06:00 [entrez]
PHST- 2016/01/31 06:00 [pubmed]
PHST- 2017/09/28 06:00 [medline]
PHST- 2018/02/27 00:00 [pmc-release]
AID - CAR-EPUB-73330 [pii]
AID - 10.2174/1567205013666160129095649 [doi]
PST - ppublish
SO  - Curr Alzheimer Res. 2016;13(7):800-8. doi: 10.2174/1567205013666160129095649.