Biomarkers – FTD Talk

Fluid Biomarkers

Our fluid biomarker team are embedded in the UK Dementia Research Institute Biomarker Lab at UCL run by Henrik Zetterberg. We also collaborate with the Mass Spectrometry Lab at the UCL Institute of Child Health run by Kevin Mills. We have recently written a review of fluid biomarkers in FTD, highlighting our work so far and our plans for the future.

Ongoing projects include:

Validation of assays to measure progranulin and related proteins
Understanding the role of neuroinflammation in FTD
Investigation of lysosomal dysfunction in FTD
Understanding synaptic health in FTD
Development of an assay for TBK1
Measurement of markers in plasma exosomes
Development of a hypothalamic peptide panel
Development of novel biomarkers of tau and TDP-43 pathology
Urinary biomarkers in FTD

We collaborate with a number of groups including the CORAL consortium.

Watch this video to see the work of the team in the lab:

Team Members

Postdoctoral Researcher

Aitana Sogorb Esteve

PhD Student

Carolin Heller

PhD Student

Rachelle Shafei

PhD Student

Imogen Swift

Research Assistant

Kathryn Knowles

Posters

AAIC 2021 (virtual, July 2021): Differential synaptic marker involvement in the different genetic forms of frontotemporal dementia
Vesicle Trafficking and Pathways to Neurodegeneration 2021 (virtual, May 2021): Differential synaptic marker involvement in the different genetic forms of frontotemporal dementia – see video description here
Vesicle Trafficking and Pathways to Neurodegeneration 2021 (virtual, May 2021): Differential patterns of lysosomal dysfunction are seen in different clinicopathological forms of primary progressive aphasia
BNA 2021 (virtual, April 2021): Differential chemokine changes are seen in the different variants of primary progressive aphasia – see video description here
ARUK 2021 (virtual, March 2021): Differential chemokine changes are seen in the different variants of primary progressive aphasia
ARUK 2021 (virtual, March 2021): A systematic review of progranulin concentrations in biofluids in over 7,000 people – assessing the pathogenicity of GRN mutations and other influencing factors
Connectome 2019 (Birmingham, October 2019): Proteomic differences in FTLD pathologies
ABN Annual Meeting (Edinburgh, May 2019): Proteomic analysis of TDP-43 pathology in frontotemporal dementia
11th ICFTD (Sydney, November 2018): Measuring novel CSF biomarkers in frontotemporal dementia
11th ICFTD (Sydney, November 2018): Plasma GFAP levels are increased in symptomatic FTD mutation carriers within the GENFI cohort
11th ICFTD (Sydney, November 2018): CSF synaptic protein concentrations are raised in those with Alzheimer’s disease pathology but not in those with FTD
First International Symposium on PSP & CBD (London, October 2018): Searching for novel CSF biomarkers of primary tauopathies
EMBO Practical Course – Quantitative proteomics (Heidelberg, June 2018): In search of novel biomarkers of frontotemporal dementia – developing a hypothalamic peptide panel
ABN Annual Meeting (Birmingham, May 2018): Cerebrospinal fluid sTREM2 levels in frontotemporal dementia differ by genetic and pathological subgroup
ARUK Conference 2018 (London, March 2018): Identification of biofluid markers of TDP-43 pathology
AAIC 2017 (London, July 2017): Serum ferritin is increased in a subset of patients with FTD
AAIC 2017 (London, July 2017): Measurement of CSF hypothalamic peptides in frontotemporal dementia
10th ICFTD (Munich, September 2016): Serum neurofilament light chain protein is a measure of disease intensity in frontotemporal dementia
ARUK 2016 (Manchester, March 2016): Serum neurofilament light chain protein is a measure of disease intensity in frontotemporal dementia

Publications

Development of a sensitive trial-ready poly(GP) CSF biomarker assay for C9orf72-associated frontotemporal dementia and amyotrophic lateral sclerosis. Wilson KM, Katona E, Glaria I, Carcolé M, Swift IJ, Sogorb-Esteve A, Heller C, Bouzigues A, Heslegrave AJ, Keshavan A, Knowles K, Patil S, Mohapatra S, Liu Y, Goyal J, Sanchez-Valle R, Laforce RJ, Synofzik M, Rowe JB, Finger E, Vandenberghe R, Butler CR, Gerhard A, Van Swieten JC, Seelaar H, Borroni B, Galimberti D, de Mendonça A, Masellis M, Tartaglia MC, Otto M, Graff C, Ducharme S, Schott JM, Malaspina A, Zetterberg H, Boyanapalli R, Rohrer JD, Isaacs AM; Genetic FTD Initiative (GENFI). J Neurol Neurosurg Psychiatry. [Epub ahead of print.]
Differential chemokine alteration in the variants of primary progressive aphasia—a role for neuroinflammation. Sogorb-Esteve A, Swift IJ, Woollacott IOC, Warren JD, Zetterberg H, Rohrer JD. J Neuroinflammation. 2021 [Epub ahead of Print].
Differential Lipid Mediator Involvement in the Different Forms of Genetic Frontotemporal Dementia: Novel Insights into Neuroinflammation. Sogorb-Esteve A, Colas RA, Dalli J, Rohrer JD. J Alzheimers Dis. 2021 [Epub ahead of Print].
Plasma glial fibrillary acidic protein and neurofilament light chain are measures of disease severity in semantic variant primary progressive aphasia. Heller C, Chan E, Foiani MS, Todd E, Russell LL, Greaves CV, Heslegrave AJ, Warren JD, Zetterberg H, Bocchetta M, Rohrer JD. J Neurol Neurosurg Psychiatry. 2020 [Epub ahead of Print].
Fluid biomarkers in frontotemporal dementia: past, present and future. Swift IJ, Sogorb-Esteve A, Heller C, Synofzik M, Otto M, Graff C, Galimberti D, Todd E, Heslegrave AJ, van der Ende EL, Van Swieten JC, Zetterberg H, Rohrer JD. J Neurol Neurosurg Psychiatry. 2021;92(2):204-215.
Cerebrospinal Fluid YKL-40 and Chitotriosidase Levels in Frontotemporal Dementia Vary by Clinical, Genetic and Pathological Subtype. Woollacott IOC, Nicholas JM, Heller C, Foiani MS, Moore KM, Russell LL, Paterson RW, Keshavan A, Schott JM, Warren JD, Heslegrave A, Zetterberg H, Rohrer JD. Dement Geriatr Cogn Disord. 2020;49(1):56-76.
Plasma glial fibrillary acidic protein is raised in progranulin-associated frontotemporal dementia. Heller C, Foiani M, Moore KM, Convery R, Bocchetta M, Neason M, Cash DM, Thomas DL, Greaves CV, Woollacott IOC, Shafei R, van Swieten J, Moreno F, Sanchez-Valle R, Borroni B, Laforce Jr R, Masellis M, Tartaglia MC, Graff C, Galimberti D, Rowe JB, Finger E, Synofzik M, Vandenberghe R, de Mendonça A, Tagliavini F, Santana I, Ducharme S, Butler C, Gerhard A, Levin J, Danek A, Frisoni GB, Sorbi S, Otto M, Heslegrave A, Zetterberg H, Rohrer JD, on behalf of GENFI. J Neurol Neurosurg Psychiatry. 2020;91(3):263-270.
CSF synaptic protein concentrations are raised in those with atypical Alzheimer’s disease but not frontotemporal dementia. Clarke MTM, Brinkmalm A, Foiani M, Woollacott IOC, Heller C, Heslegrave A, Keshavan A, Fox NC, Schott JM, Warren JD, Blennow K, Zetterberg H, Jonathan Rohrer JD. Alzheimers Res Ther. 2019;11(1):105.
Searching for novel cerebrospinal fluid biomarkers of tau pathology in frontotemporal dementia: an elusive quest. Foiani MS, Cicognola C, Ermann N, Woollacott IOC, Heller C, Heslegrave AJ, Keshavan A, Paterson RW, Ye K, Kornhuber J, Fox NC, Schott JM, Warren JD, Lewczuk P, Zetterberg H, Blennow K, Höglund K, Rohrer JD. J Neurol Neurosurg Psychiatry. 2019;90(7):740-746.
Review: Fluid Biomarkers for Frontotemporal Dementias. Zetterberg H, van Swieten JC, Boxer AL, Rohrer JD. Neuropathol Appl Neurobiol. 2019;45(1):81-87.
Cerebrospinal fluid soluble TREM2 levels in frontotemporal dementia differ by genetic and pathological subgroup. Woollacott IOC, Nicholas JM, Heslegrave A, Heller C, Foiani MS, Dick KM, Russell LL, Paterson RW, Keshavan A, Fox NC, Warren JD, Schott JM, Zetterberg H, Rohrer JD. Alzheimers Res Ther. 2018;10(1):79.
Plasma tau is increased in frontotemporal dementia. Foiani MS, Woollacott IO, Heller C, Bocchetta M, Heslegrave A, Dick KM, Russell LL, Marshall CR, Mead S, Schott JM, Fox NC, Warren JD, Zetterberg H, Rohrer JD. J Neurol Neurosurg Psychiatry. 2018;89(8):804-807.
CSF pro-orexin and amyloid-b38 expression in Alzheimer’s disease and frontotemporal dementia. Heywood WE, Hallqvist J, Heslegrave AJ, Zetterberg H, Fenoglio C, Scarpini E, Rohrer JD, Galimberti D, Mills K. Neurobiol Aging. 2018;72:171-176.
Serum neurofilament light chain protein is a measure of disease intensity in frontotemporal dementia. Rohrer JD, Woollacott IO, Dick KM, Brotherhood E, Gordon E, Fellows A, Toombs J, Druyeh R, Cardoso MJ, Ourselin S, Nicholas JM, Norgren N, Mead S, Andreasson U, Blennow K, Schott JM, Fox NC, Warren JD, Zetterberg H. Neurology. 2016;87(13):1329-36.