CSF sTREM2 is elevated in a subset in GRN-related frontotemporal dementia

Emma L. van der Ende, Estrella Morenas-Rodriguez, Corey McMillan, Murray Grossman, David Irwin, Raquel Sanchez-Valle, Caroline Graff, Rik Vandenberghe, Yolande A. L. Pijnenburg, Robert Laforce, Isabelle Le Ber, Alberto Lleo, Christian Haass, Marc Suarez-Calvet, John C. van Swieten, Harro Seelaar*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Excessive microglial activation might be a central pathological process in GRN-related frontotemporal dementia (FTD-GRN). We measured soluble triggering receptor expressed on myeloid cells 2 (sTREM2), which is shed from disease-associated microglia following cleavage of TREM2, in cerebrospinal fluid of 34 presymptomatic and 35 symptomatic GRN mutation carriers, 6 presymptomatic and 32 symptomatic C9orf72 mutation carriers and 67 healthy noncarriers by ELISA. Although no group differences in sTREM2 levels were observed (GRN: symptomatic (median 5.2 ng/mL, interquartile range [3.9–9.2]) vs. presymptomatic (4.3 ng/mL [2.6–6.1]) vs. noncarriers (4.2 ng/mL [2.6–5.5]): p = 0.059; C9orf72: symptomatic (4.3 [2.9–7.0]) vs. presymptomatic (3.2 [2.2–4.2]) vs. noncarriers: p = 0.294), high levels were seen in a subset of GRN, but not C9orf72, mutation carriers, which might reflect differential TREM2-related microglial activation. Interestingly, 2 presymptomatic carriers with low sTREM2 levels developed symptoms after 1 year, whereas 2 with high levels became symptomatic after >5 years. While sTREM2 is not a promising diagnostic biomarker for FTD-GRN or FTD-C9orf72, further research might elucidate its potential to monitor microglial activity and predict disease progression.
Original languageEnglish
Pages (from-to)158.e1-158.e5
JournalNeurobiology of Aging
Volume103
DOIs
Publication statusPublished - 1 Jul 2021

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