Cerebrospinal fluid soluble TREM2 levels in frontotemporal dementia differ by genetic and pathological subgroup
Ione OC Woollacott1, Jennifer M Nicholas2, Amanda Heslegrave3,4 Carolin Heller3,4, Martha S Foiani3,4, Katrina M Dick1, Lucy L Russell1, Ross W Paterson1, Ashvini Keshavan1, Nick C Fox FRCP1,4, Jason D Warren1, Jonathan M Schott1, Henrik Zetterberg3,4,5,6, Jonathan D Rohrer1 1Dementia Research Centre, Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK; 2Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK; 3Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, UK; 4UK Dementia Research Institute, London, UK; 5Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; 6Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden
Background:Cerebrospinal fluid (CSF) soluble triggering receptor expressed on myeloid cells 2 (sTREM2) levels are elevated in Alzheimer's disease (AD) but have not been fully explored in frontotemporal dementia (FTD). We examined CSF sTREM2 levels in FTD and healthy controls. Methods: CSF sTREM2 and AD biomarker (T-tau, P-tau and Aβ42) levels were measured using immunoassay in 17 controls and 64 individuals with FTD (behavioural variant FTD or primary progressive aphasia; 10 with familial FTD). Multivariable regressions compared sTREM2 levels between FTD and controls and across clinical and genetic FTD subtypes, and explored relationships with AD CSF biomarkers. Results: CSF sTREM2 levels did not differ overall between FTD and controls, or between clinical FTD subgroups. However, progranulin mutation carriers had higher sTREM2 levels than controls and other mutation carriers. CSF sTREM2 levels were also higher in individuals with FTD and AD-like CSF than those with non-AD-like CSF, and were associated with CSF T-tau levels in controls and FTD, but with T-tau and P-tau levels in FTD with AD-like CSF. Conclusions: Although CSF sTREM2 levels are not raised in FTD overall, they are higher in individuals with progranulin mutations or AD pathology, perhaps due to more intense microglial activation. CSF sTREM2 levels correlate with a marker of neuronal injury therefore could be a promising biomarker of disease intensity in future studies of FTD.
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