%0 Journal Article
%A van der Ende, Emma L
%A Morenas-Rodriguez, Estrella
%A McMillan, Corey
%A Grossman, Murray
%A Irwin, David
%A Sanchez-Valle, Raquel
%A Graff, Caroline
%A Vandenberghe, Rik
%A Pijnenburg, Yolande A L
%A Laforce, Robert
%A Ber, Isabelle Le
%A Lleo, Alberto
%A Haass, Christian
%A Suarez-Calvet, Marc
%A van Swieten, John C
%A Seelaar, Harro
%T CSF sTREM2 is elevated in a subset in GRN-related frontotemporal dementia.
%J Neurobiology of aging
%V 103
%@ 0197-4580
%C Amsterdam [u.a.]
%I Elsevier Science
%M DZNE-2021-00888
%P 158.e1 - 158.e5
%D 2021
%X 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.
%K Adult
%K Aged
%K Biomarkers: cerebrospinal fluid
%K C9orf72 Protein: genetics
%K Female
%K Frontotemporal Dementia: diagnosis
%K Frontotemporal Dementia: genetics
%K Heterozygote
%K Humans
%K Male
%K Membrane Glycoproteins: cerebrospinal fluid
%K Membrane Glycoproteins: metabolism
%K Microglia: metabolism
%K Microglia: physiology
%K Middle Aged
%K Mutation
%K Progranulins: genetics
%K Receptors, Immunologic: metabolism
%K Biomarker (Other)
%K Cerebrospinal fluid (Other)
%K Frontotemporal dementia (Other)
%K Microglia (Other)
%K sTREM2 (Other)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:33896652
%R 10.1016/j.neurobiolaging.2021.02.024
%U https://pub.dzne.de/record/155720