Journal Article

DZNE-2021-00888

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png CSF sTREM2 is elevated in a subset in GRN-related frontotemporal dementia.

van der Ende, E. L. ; Morenas-Rodriguez, E.DZNE* ; McMillan, C. ; Grossman, M. ; Irwin, D. ; Sanchez-Valle, R. ; Graff, C. ; Vandenberghe, R. ; Pijnenburg, Y. A. L. ; Laforce, R. ; Ber, I. L. ; Lleo, A. ; Haass, C.DZNE* ; Suarez-Calvet, M.DZNE* ; van Swieten, J. C. ; Seelaar, H.

2021
Elsevier Science Amsterdam [u.a.]

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Please use a persistent id in citations: doi:10.1016/j.neurobiolaging.2021.02.024

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.

Keyword(s): Adult (MeSH) ; Aged (MeSH) ; Biomarkers: cerebrospinal fluid (MeSH) ; C9orf72 Protein: genetics (MeSH) ; Female (MeSH) ; Frontotemporal Dementia: diagnosis (MeSH) ; Frontotemporal Dementia: genetics (MeSH) ; Heterozygote (MeSH) ; Humans (MeSH) ; Male (MeSH) ; Membrane Glycoproteins: cerebrospinal fluid (MeSH) ; Membrane Glycoproteins: metabolism (MeSH) ; Microglia: metabolism (MeSH) ; Microglia: physiology (MeSH) ; Middle Aged (MeSH) ; Mutation (MeSH) ; Progranulins: genetics (MeSH) ; Receptors, Immunologic: metabolism (MeSH) ; Biomarker ; Cerebrospinal fluid ; Frontotemporal dementia ; Microglia ; sTREM2

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Contributing Institute(s):

1. Molecular Neurodegeneration (AG Haass)

Research Program(s):

1. 352 - Disease Mechanisms (POF4-352) (POF4-352)

Appears in the scientific report 2021

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