MicroRNAs in CSF as prodromal biomarkers for Huntington disease in the PREDICT-HD study

Eric R Reed; Jeanne C Latourelle; Jeremy H Bockholt; Joli Bregu; Justin Smock; Jane S Paulsen; Richard H Myers; PREDICT-HD CSF ancillary study investigators

doi:10.1212/WNL.0000000000004844

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MicroRNAs in CSF as prodromal biomarkers for Huntington disease in the PREDICT-HD study

Journal article

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MicroRNAs in CSF as prodromal biomarkers for Huntington disease in the PREDICT-HD study

Eric R Reed, Jeanne C Latourelle, Jeremy H Bockholt, Joli Bregu, Justin Smock, Jane S Paulsen, Richard H Myers and PREDICT-HD CSF ancillary study investigators

Neurology, Vol.90(4), pp.e264-e272

01/23/2018

DOI: 10.1212/WNL.0000000000004844

PMCID: PMC5798654

PMID: 29282329

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Abstract

To investigate the feasibility of microRNA (miRNA) levels in CSF as biomarkers for prodromal Huntington disease (HD). miRNA levels were measured in CSF from 60 PREDICT-HD study participants using the HTG protocol. Using a CAG-Age Product score, 30 prodromal HD participants were selected based on estimated probability of imminent clinical diagnosis of HD (i.e., low, medium, high; n = 10/group). For comparison, participants already diagnosed (n = 15) and healthy controls (n = 15) were also selected. A total of 2,081 miRNAs were detected and 6 were significantly increased in the prodromal HD gene expansion carriers vs controls at false discovery rate q < 0.05 (miR-520f-3p, miR-135b-3p, miR-4317, miR-3928-5p, miR-8082, miR-140-5p). Evaluating the miRNA levels in each of the HD risk categories, all 6 revealed a pattern of increasing abundance from control to low risk, and from low risk to medium risk, which then leveled off from the medium to high risk and HD diagnosed groups. This study reports miRNAs as CSF biomarkers of prodromal and diagnosed HD. Importantly, miRNAs were detected in the prodromal HD groups furthest from diagnosis where treatments are likely to be most consequential and meaningful. The identification of potential biomarkers in the disease prodrome may prove useful in evaluating treatments that may postpone disease onset. NCT00051324.

Details

Title: Subtitle: MicroRNAs in CSF as prodromal biomarkers for Huntington disease in the PREDICT-HD study
Creators: Eric R Reed - From the Bioinformatics Program (E.R.R., R.H.M.), Boston University; Department of Neurology (J.C.L., J.B., R.H.M.), Boston University School of Medicine, MA; and Departments of Neurology and Psychiatry (J.H.B., J.S.P.) and Internal Medicine (J.S.), Carver College of Medicine, University of Iowa, Iowa City
Jeanne C Latourelle - From the Bioinformatics Program (E.R.R., R.H.M.), Boston University; Department of Neurology (J.C.L., J.B., R.H.M.), Boston University School of Medicine, MA; and Departments of Neurology and Psychiatry (J.H.B., J.S.P.) and Internal Medicine (J.S.), Carver College of Medicine, University of Iowa, Iowa City
Jeremy H Bockholt - From the Bioinformatics Program (E.R.R., R.H.M.), Boston University; Department of Neurology (J.C.L., J.B., R.H.M.), Boston University School of Medicine, MA; and Departments of Neurology and Psychiatry (J.H.B., J.S.P.) and Internal Medicine (J.S.), Carver College of Medicine, University of Iowa, Iowa City
Joli Bregu - From the Bioinformatics Program (E.R.R., R.H.M.), Boston University; Department of Neurology (J.C.L., J.B., R.H.M.), Boston University School of Medicine, MA; and Departments of Neurology and Psychiatry (J.H.B., J.S.P.) and Internal Medicine (J.S.), Carver College of Medicine, University of Iowa, Iowa City
Justin Smock - From the Bioinformatics Program (E.R.R., R.H.M.), Boston University; Department of Neurology (J.C.L., J.B., R.H.M.), Boston University School of Medicine, MA; and Departments of Neurology and Psychiatry (J.H.B., J.S.P.) and Internal Medicine (J.S.), Carver College of Medicine, University of Iowa, Iowa City
Jane S Paulsen - From the Bioinformatics Program (E.R.R., R.H.M.), Boston University; Department of Neurology (J.C.L., J.B., R.H.M.), Boston University School of Medicine, MA; and Departments of Neurology and Psychiatry (J.H.B., J.S.P.) and Internal Medicine (J.S.), Carver College of Medicine, University of Iowa, Iowa City. rmyers@bu.edu jane-paulsen@uiowa.edu
Richard H Myers - From the Bioinformatics Program (E.R.R., R.H.M.), Boston University; Department of Neurology (J.C.L., J.B., R.H.M.), Boston University School of Medicine, MA; and Departments of Neurology and Psychiatry (J.H.B., J.S.P.) and Internal Medicine (J.S.), Carver College of Medicine, University of Iowa, Iowa City. rmyers@bu.edu jane-paulsen@uiowa.edu
PREDICT-HD CSF ancillary study investigators
Resource Type: Journal article
Publication Details: Neurology, Vol.90(4), pp.e264-e272
DOI: 10.1212/WNL.0000000000004844
PMID: 29282329
PMCID: PMC5798654
NLM abbreviation: Neurology
ISSN: 0028-3878
eISSN: 1526-632X
Grant note: R01 NS103475 / NINDS NIH HHS
Language: English
Date published: 01/23/2018
Academic Unit: Psychiatry; Psychological and Brain Sciences; General Internal Medicine; Internal Medicine
Record Identifier: 9984083276602771

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