eprintid: 10051777
rev_number: 18
eprint_status: archive
userid: 608
dir: disk0/10/05/17/77
datestamp: 2018-07-11 17:20:45
lastmod: 2021-09-20 22:22:51
status_changed: 2018-07-11 17:20:45
type: article
metadata_visibility: show
creators_name: Portelius, E
creators_name: Olsson, B
creators_name: Höglund, K
creators_name: Cullen, NC
creators_name: Kvartsberg, H
creators_name: Andreasson, U
creators_name: Zetterberg, H
creators_name: Sandelius, Å
creators_name: Shaw, LM
creators_name: Lee, VMY
creators_name: Irwin, DJ
creators_name: Grossman, M
creators_name: Weintraub, D
creators_name: Chen-Plotkin, A
creators_name: Wolk, DA
creators_name: McCluskey, L
creators_name: Elman, L
creators_name: McBride, J
creators_name: Toledo, JB
creators_name: Trojanowski, JQ
creators_name: Blennow, K
title: Cerebrospinal fluid neurogranin concentration in neurodegeneration: relation to clinical phenotypes and neuropathology
ispublished: inpress
divisions: UCL
divisions: B02
divisions: C07
divisions: D07
divisions: F86
keywords: Alzheimer’s disease, Biomarker, Cerebrospinal fluid, Neurogranin, Neuropathology
note: Copyright © The Author(s) 2018
Open Access
This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
abstract: Neurogranin (Ng) is a post-synaptic protein that previously has been shown to be a biomarker for synaptic function when measured in cerebrospinal fluid (CSF). The CSF concentration of Ng is increased in Alzheimer's disease dementia (ADD), and even in the pre-dementia stage. In this prospective study, we used an enzyme-linked immunosorbent assay that quantifies Ng in CSF to test the performance of Ng as a marker of synaptic function. In 915 patients, CSF Ng was evaluated across several different neurodegenerative diseases. Of these 915 patients, 116 had a neuropathologically confirmed definitive diagnosis and the relation between CSF Ng and topographical distribution of different pathologies in the brain was evaluated. CSF Ng was specifically increased in ADD compared to eight other neurodegenerative diseases, including Parkinson's disease (p < 0.0001), frontotemporal dementia (p < 0.0001), and amyotrophic lateral sclerosis (p = 0.0002). Similar results were obtained in neuropathologically confirmed cases. Using a biomarker index to evaluate whether CSF Ng contributed diagnostic information to the core AD CSF biomarkers (amyloid β (Aβ), t-tau, and p-tau), we show that Ng significantly increased the discrimination between AD and several other disorders. Higher CSF Ng levels were positively associated with greater Aβ neuritic plaque (Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuritic plaque score, p = 0.0002) and tau tangle pathology (Braak neurofibrillary tangles staging, p = 0.0007) scores. In the hippocampus and amygdala, two brain regions heavily affected in ADD with high expression of Ng, CSF Ng was associated with plaque (p = 0.0006 and p < 0.0001), but not with tangle, α-synuclein, or TAR DNA-binding protein 43 loads. These data support that CSF Ng is increased specifically in ADD, that high CSF Ng concentrations likely reflect synaptic dysfunction and that CSF Ng is associated with β-amyloid plaque pathology.
date: 2018-04-26
date_type: published
official_url: http://doi.org/10.1007/s00401-018-1851-x
oa_status: green
full_text_type: pub
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 1553072
doi: 10.1007/s00401-018-1851-x
pii: 10.1007/s00401-018-1851-x
lyricists_name: Zetterberg, Henrik
lyricists_id: HZETT94
actors_name: Cuccu, Clara
actors_id: CCCUC40
actors_role: owner
full_text_status: public
publication: Acta Neuropathologica
event_location: Germany
issn: 1432-0533
citation:        Portelius, E;    Olsson, B;    Höglund, K;    Cullen, NC;    Kvartsberg, H;    Andreasson, U;    Zetterberg, H;                                                         ... Blennow, K; + view all <#>        Portelius, E;  Olsson, B;  Höglund, K;  Cullen, NC;  Kvartsberg, H;  Andreasson, U;  Zetterberg, H;  Sandelius, Å;  Shaw, LM;  Lee, VMY;  Irwin, DJ;  Grossman, M;  Weintraub, D;  Chen-Plotkin, A;  Wolk, DA;  McCluskey, L;  Elman, L;  McBride, J;  Toledo, JB;  Trojanowski, JQ;  Blennow, K;   - view fewer <#>    (2018)    Cerebrospinal fluid neurogranin concentration in neurodegeneration: relation to clinical phenotypes and neuropathology.                   Acta Neuropathologica        10.1007/s00401-018-1851-x <https://doi.org/10.1007/s00401-018-1851-x>.    (In press).    Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10051777/1/Portelius2018_Article_CerebrospinalFluidNeurograninC.pdf