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O5‐05‐06: GENETIC AND EPIGENETIC BLOOD SIGNATURE OF MILD COGNITIVE IMPAIRMENT IN PRODROMAL ALZHEIMER'S DISEASE
Author(s) -
Chag Yvon,
Ferland Guylaine,
Belleville Sylvie,
Morais José A.,
Payette Hélène,
Hudon Carol,
Potvin Olivier,
Gaudreau Pierrette
Publication year - 2014
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2014.04.505
Subject(s) - epigenetics , dna methylation , dementia , oncology , cohort , methylation , gene , body mass index , medicine , gene expression , disease , bioinformatics , biology , genetics
with high expression in particular brain regions, including the cortex and hippocampus. Research targeting the pathophysiological mechanisms responsible for the cognitive deterioration, which is a hallmark in Alzheimer’s disease (AD), indicates that synaptic degradation is a major contributor to neuronal loss. Neuronal loss is in turn thought to be one of the underlying causes in AD development and progression. Synaptic degeneration is believed to occur early in the course of the disease, probably long before the onset of the first symptoms. Thus, the cerebrospinal fluid (CSF) levels of neurogranin may enable earlier diagnosis Methods: CSF from healthy controls and AD patients was analysed by immunoprecipitation (IP) followed by MALDI-TOF/TOF mass spectrometry. The IP was performed using in-house-generated mouse anti-human neurogranin antibodies targeting the C-terminal region of the protein. Quantification of endogenous neurogranin peptides was performed by adding an isotopic labelled neurogranin peptide to the CSF prior any sample preparation. Results: A variety of endogenous neurogranin peptides including Ng48-75 and Ng48-76 were reproducible identified in CSF while full length neurogranin could not be detected. A pilot study on CSF from AD patients (n1⁄416) and age matched healthy controls (n1⁄410) showed significantly increased levels of Ng48-75 and Ng48-76 (p1⁄40.01 and 0.002, respectively) in AD as compared to controls. In addition, the mass spectrometric results correlated with the two established AD biomarkers total Tau and phosphorylated Tau protein. Conclusions: Neurogranin is metabolised into several short endogenous peptides which can be detected and quantified in CSF. Results from a small pilot study including AD patients and healthy controls showed significantly increased levels of the two endogenous peptides, Ng48-75 and Ng48-76, suggesting that neurogranin can be used as a novel biomarker marker for AD.