Identifying the role of neuroinflammation in frontotemporal dementia – a pathological and cerebrospinal fluid biomarker study
Award Number
MR/M018288/1Award Type
FellowshipStatus / Stage
ActiveDates
5 August 2015 -4 August 2018
Duration (calculated)
02 years 11 monthsFunder(s)
MRC (UKRI)Funding Amount
£220,957.58Funder/Grant study page
MRC UKRIContracted Centre
University College LondonPrincipal Investigator
Dr Woollacott, Ione OliviaWHO Catergories
Development of BiomarkersUnderstanding Underlying Disease
Disease Type
Frontotemporal Dementia (FTD)CPEC Review Info
| Reference ID | 264 |
|---|---|
| Researcher | Reside Team |
| Published | 12/06/2023 |
Data
| Award Number | MR/M018288/1 |
|---|---|
| Status / Stage | Active |
| Start Date | 20150805 |
| End Date | 20180804 |
| Duration (calculated) | 02 years 11 months |
| Funder/Grant study page | MRC UKRI |
| Contracted Centre | University College London |
| Funding Amount | £220,957.58 |
Abstract
Frontotemporal dementia (FTD) is a unique neurodegenerative syndrome characterised by progressive impairments of behaviour, social or language functioning. Although most patients have a sporadic form of FTD, a third of patients have an underlying mutation in one of three main genes: MAPT, C9ORF72 or GRN. We do not fully understand the steps in FTD disease pathogenesis, and there are no effective treatments. Previous research suggests a role for neuroinflammatory mechanisms in FTD, with small studies showing altered levels of inflammatory markers in brain tissue and cerebrospinal fluid (CSF) samples from patients with FTD. This project aims to identify CSF biomarkers of neuroinflammation in patients with FTD and to investigate their relationship with measures of disease severity and progression. Post-mortem brain tissue from patients with both genetic and sporadic FTD as well as healthy controls will be used initially to identify abnormalities in neuroinflammatory pathways. Assays of candidate biomarkers identified in these analyses will then be developed and tested in CSF samples from groups of patients with genetic subtypes of FTD, their presymptomatic relatives, sporadic FTD cases and healthy controls. These results will be used to examine whether such markers correlate with measures of disease severity and/or progression established from clinical and neuroimaging analyses. CSF biomarkers identified in this project, once validated, might be used to develop novel therapeutic targets, guide clinical trials of future or existing anti-inflammatory therapies, and predict more accurately progression of disease and response to treatment in sporadic or genetic forms of FTD.
Aims
This project aims to identify CSF biomarkers of neuroinflammation in patients with FTD and to investigate their relationship with measures of disease severity and progression. Post-mortem brain tissue from patients with both genetic and sporadic FTD as well as healthy controls will be used initially to identify abnormalities in neuroinflammatory pathways. Assays of candidate biomarkers identified in these analyses will then be developed and tested in CSF samples from groups of patients with genetic subtypes of FTD, their presymptomatic relatives, sporadic FTD cases and healthy controls. These results will be used to examine whether such markers correlate with measures of disease severity and/or progression established from clinical and neuroimaging analyses. CSF biomarkers identified in this project, once validated, might be used to develop novel therapeutic targets, guide clinical trials of future or existing anti-inflammatory therapies, and predict more accurately progression of disease and response to treatment in sporadic or genetic forms of FTD.