Author:

Keywords:

Science & Technology, Life Sciences & Biomedicine, Geriatrics & Gerontology, Neurosciences, Neurosciences & Neurology, Frontotemporal dementia, Biomarker, Cerebrospinal fluid, Microglia, sTREM2, FLUID SOLUBLE TREM2, CEREBROSPINAL-FLUID, ALZHEIMERS-DISEASE, PROGRANULIN, MICROGLIA, VARIANT, INJURY, Adult, Aged, Biomarkers, C9orf72 Protein, Female, Frontotemporal Dementia, Heterozygote, Humans, Male, Membrane Glycoproteins, Middle Aged, Mutation, Progranulins, Receptors, Immunologic, 1103 Clinical Sciences, 1109 Neurosciences, Neurology & Neurosurgery, 3209 Neurosciences, 5202 Biological psychology

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.