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

Neurobiol Aging. 2021 Mar 4:S0197-4580(21)00079-8. doi: 10.1016/j.neurobiolaging.2021.02.024. Epub ahead of print. PMID: 33896652.

Authors/Editors: van der Ende EL, Morenas-Rodriguez E, McMillan C, Grossman M, Irwin D, Sanchez-Valle R, Graff C, Vandenberghe R, Pijnenburg YAL, Laforce R, Ber IL, Lleo A, Haass C, Suarez-Calvet M, van Swieten JC, Seelaar H.
Publication Date: 2021


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.

Keywords: Biomarker; Cerebrospinal fluid; Frontotemporal dementia; Microglia; sTREM2.


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