TY  - JOUR
KW  - All Genetics
KW  -  All Cognitive Disorders/Dementia
KW  -  Cerebrospinal Fluid
KW  -  Frontotemporal Dementia
N2  - OBJECTIVE: A rare cause of familial frontotemporal dementia (FTD) is a mutation in the CHMP2B gene on chromosome 3 (FTD-3), described in a Danish family. Here we examine whether CSF biomarkers change in the preclinical phase of the disease. METHODS: In this cross-sectional explorative study, we analyzed CSF samples from 16 mutation carriers and 14 noncarriers from the Danish FTD-3 family. CSF biomarkers included total tau (t-tau) and neurofilament light chain (NfL) as a marker for neurodegeneration, phosphorylated tau (p-tau) as a marker for tau pathology, ?-amyloid (A?) 38, 40, and 42 (A???, A???, and A???). to monitor A? metabolism, and YKL-40 as a marker of neuroinflammation. A? isoform concentrations were measured using a multiplexed immunoassay; t-tau, p-tau, NfL, and YKL-40 concentrations were measured using sandwich ELISAs. RESULTS: CSF NfL concentration was significantly increased in mutation carriers vs noncarriers. Further, CSF NfL concentration was significantly higher in symptomatic mutation carriers compared to presymptomatic carriers, and also significantly higher in presymptomatic carriers compared to noncarriers. No differences in t-tau and p-tau and YKL-40 concentrations between controls and mutation carriers were observed. CSF concentrations of the A? peptides A??? and A??? but not A??? were significantly lower in mutation carriers compared to noncarriers. CONCLUSIONS: Increased NfL levels in presymptomatic individuals and in symptomatic patients with FTD-3 indicate a continuous process of neurodegeneration from the presymptomatic to symptomatic state. Although not specific for FTD-3 pathology, our data suggest that CSF NfL could serve as a valuable biomarker to detect onset of neurodegeneration in FTD-3 mutation carriers.
ID  - discovery10051932
PB  - LIPPINCOTT WILLIAMS & WILKINS
TI  - CSF neurofilament light concentration is increased in presymptomatic CHMP2B mutation carriers
AV  - public
Y1  - 2018/01/09/
EP  - e163
JF  - Neurology
A1  - Rostgaard, N
A1  - Roos, P
A1  - Portelius, E
A1  - Blennow, K
A1  - Zetterberg, H
A1  - Simonsen, AH
A1  - Nielsen, JE
UR  - https://doi.org/10.1212/WNL.0000000000004799
SN  - 0028-3878
IS  - 2
N1  - © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/).
VL  - 90
SP  - e157
ER  -