Downregulation of exosomal miR-204-5p and miR-632 as a biomarker for FTD: a GENFI study

被引：51

作者：

Schneider, Raphael ^{[1
,2
]}

McKeever, Paul ^{[1
,2
]}

Kim, TaeHyung ^{[3
,4
]}

Graff, Caroline ^{[5
]}

van Swieten, John Cornelis ^{[6
]}

Karydas, Anna ^{[7
]}

Boxer, Adam ^{[7
]}

Rosen, Howie ^{[7
]}

Miller, Bruce L. ^{[7
]}

Laforce, Robert, Jr. ^{[8
]}

Galimberti, Daniela ^{[9
]}

Masellis, Mario ^{[10
,11
]}

Borroni, Barbara ^{[12
]}

Zhang, Zhaolei ^{[4
,13
]}

Zinman, Lorne ^{[11
]}

Rohrer, Jonathan Daniel ^{[14
]}

Tartaglia, Maria Carmela ^{[2
,15
]}

Robertson, Janice ^{[1
,2
]}

机构：

[1] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada

[2] Univ Toronto, Tanz Ctr Res Neurodegenerat Dis, Toronto, ON M5T 2S8, Canada

[3] Univ Toronto, Dept Comp Sci, Toronto, ON, Canada

[4] Univ Toronto, Donnelly Ctr Cellular & Biomol Res, Toronto, ON, Canada

[5] Karolinska Inst, Dept Neurobiol, Stockholm, Sweden

[6] Erasmus MC, Dept Neurol, Rotterdam, Netherlands

[7] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA

[8] Univ Laval, Dept Sci Neurol, Quebec City, PQ, Canada

[9] Univ Milan, Ctr Dino Ferrari, Fdn Ca Granda IRCCS Osped Policlin, Milan, Italy

[10] Univ Toronto, LC Campbell Cognit Neurol Res Unit, Toronto, ON, Canada

[11] Univ Toronto, Sunnybrook Hlth Sci Ctr, Toronto, ON, Canada

[12] Univ Brescia, Neurol Unit, Ctr Ageing Brain & Neurodegenerat Disorders, Brescia, Italy

[13] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada

[14] UCL, Dementia Res Ctr, London, England

[15] Univ Hlth Network, Memory Clin, Toronto, ON, Canada

来源：

JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY | 2018年 / 89卷 / 08期

基金：

加拿大健康研究院; 英国医学研究理事会; 美国国家卫生研究院;

关键词：

FRONTOTEMPORAL LOBAR DEGENERATION; AMYOTROPHIC-LATERAL-SCLEROSIS; PROGRANULIN DEFICIENCY; COMPREHENSIVE ATLAS; ALZHEIMERS-DISEASE; NEURITE OUTGROWTH; DEMENTIA; CELLS; EXPRESSION; PATHWAYS;

D O I：

10.1136/jnnp-2017-317492

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Objective To determine whether exosomal microRNAs (miRNAs) in cerebrospinal fluid (CSF) of patients with frontotemporal dementia (FTD) can serve as diagnostic biomarkers, we assessed miRNA expression in the Genetic Frontotemporal Dementia Initiative (GENFI) cohort and in sporadic FTD. Methods GENFI participants were either carriers of a pathogenic mutation in progranulin, chromosome 9 open reading frame 72 or microtubule-associated protein tau or were at risk of carrying a mutation because a first-degree relative was a known symptomatic mutation carrier. Exosomes were isolated from CSF of 23 presymptomatic and 15 symptomatic mutation carriers and 11 healthy non-mutation carriers. Expression of 752 miRNAs was measured using quantitative PCR (qPCR) arrays and validated by qPCR using individual primers. MiRNAs found differentially expressed in symptomatic compared with presymptomatic mutation carriers were further evaluated in a cohort of 17 patients with sporadic FTD, 13 patients with sporadic Alzheimer's disease (AD) and 10 healthy controls (HCs) of similar age. Results In the GENFI cohort, miR-204-5p and miR-632 were significantly decreased in symptomatic compared with presymptomatic mutation carriers. Decrease of miR-204-5p and miR-632 revealed receiver operator characteristics with an area of 0.89 (90% CI 0.79 to 0.98) and 0.81 (90% CI 0.68 to 0.93), respectively, and when combined an area of 0.93 (90% CI 0.87 to 0.99). In sporadic FTD, only miR-632 was significantly decreased compared with AD and HCs. Decrease of miR-632 revealed an area of 0.90 (90% CI 0.81 to 0.98). Conclusions Exosomal miR-204-5p and miR-632 have potential as diagnostic biomarkers for genetic FTD and miR-632 also for sporadic FTD.

引用

页码：851 / 858

页数：8

共 42 条

[1] Progranulin deficiency induces overactivation of WNT5A expression via TNF-α/NF-κB pathway in peripheral cells from frontotemporal dementia-linked granulin mutation carriers [J].