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

2021; Elsevier BV; Volume: 103; Linguagem: Inglês

10.1016/j.neurobiolaging.2021.02.024

1558-1497

Emma L. van der Ende, Estrella Morenas‐Rodríguez, Corey T. McMillan, Murray Grossman, David J. Irwin, Raquel Sánchez‐Valle, Caroline Graff, Rik Vandenberghe, Yolande A.L. Pijnenburg, Robert Laforce, Isabelle Le Ber, Alberto Lleó, Christian Haass, Marc Suárez‐Calvet, John C. van Swieten, Harro Seelaar,

Neurological Disease Mechanisms and Treatments

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.