Low-variance RNAs identify Parkinson's disease molecular signature in blood

Movement Disorders : Official Journal of the Movement Disorder Society
Maria D ChikinaStuart C Sealfon

Abstract

The diagnosis of Parkinson's disease (PD) is usually not established until advanced neurodegeneration leads to clinically detectable symptoms. Previous blood PD transcriptome studies show low concordance, possibly resulting from the use of microarray technology, which has high measurement variation. The Leucine-rich repeat kinase 2 (LRRK2) G2019S mutation predisposes to PD. Using preclinical and clinical studies, we sought to develop a novel statistically motivated transcriptomic-based approach to identify a molecular signature in the blood of Ashkenazi Jewish PD patients, including LRRK2 mutation carriers. Using a digital gene expression platform to quantify 175 messenger RNA (mRNA) markers with low coefficients of variation (CV), we first compared whole-blood transcript levels in mouse models (1) overexpressing wild-type (WT) LRRK2, (2) overexpressing G2019S LRRK2, (3) lacking LRRK2 (knockout), and (4) and in WT controls. We then studied an Ashkenazi Jewish cohort of 34 symptomatic PD patients (both WT LRRK2 and G2019S LRRK2) and 32 asymptomatic controls. The expression profiles distinguished the four mouse groups with different genetic background. In patients, we detected significant differences in blood transcript levels bo...Continue Reading

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Citations

Dec 3, 2016·Journal of the International Neuropsychological Society : JINS·Christine A Cooper, Lama M Chahine
Dec 1, 2017·Cell and Tissue Research·Enrico Glaab
Sep 17, 2017·Neurology·Ron ShamirDimitri Krainc
Nov 20, 2016·Bioanalysis·Marcia Cristina Teixeira Dos SantosAndre Nogueira da Costa

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