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O5‐05‐05: MASS SPECTROMETRIC PROFILING OF ENDOGENOUS PEPTIDES DERIVED FROM THE POST‐SYNAPTIC PROTEIN NEUROGRANIN IN CEREBROSPINAL FLUID
Author(s) -
Schmidt Hlin Johansson,
Andreasen Neils,
Zetterberg Henrik,
Blennow Kaj,
Portelius Erik
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.2014.04.504
Subject(s) - neurogranin , cerebrospinal fluid , chemistry , endogeny , hippocampus , medicine , endocrinology , neuroscience , psychology , biochemistry , phosphorylation , protein kinase c
misfolded proteins. Currently there is no consensus for blood based tests for these diseases. Expression profiling of small non-coding RNA’s, microRNA (miRNA), has revealed diagnostic potential in human disease such as cancer. miRNA’s can be found in the blood stream and other body fluids encapsulated in small extracellular vesicles known as exosomes.Methods: Using deep sequencing we have analysed the RNA content of exosomes from a cohort of healthy aged and Alzheimer’s patients (n1⁄449) using samples from the Australian Imaging, Biomarkers and Lifestyle Flagship Study (AIBL). miRNA associating with disease were validated using qPCR(N1⁄460), with predictions performed using RandomForest. Additional risk factors collected during the 4.5 year AIBL study were included, which consisted of baseline and 54 month clinical, medical and cognitive assessment including Amyloid-PET imaging. Results:We developed a workflow for the analysis of exosomal miRNA from human blood serum that has diagnostic potential for AD. We have identified an AD specific, 16 miRNA signature, derived from the deep sequencing data and validated in an additional set of samples. Adding established risk factors including age, sex, and APOE allele status to the panel of deregulated miRNA resulted in a sensitivity and specificity of 87% and 77% respectively for predicting AD. Furthermore, Amyloid-PET information for those HC participants incorrectly classified with AD suggested progression towards AD. Conclusions: These data suggest that an exosomal miRNA signature may be a suitable peripheral screening tool for AD and other neurodegenerative disorders such as Prion and Parkinson’s diseases.