TY  - JOUR
AU  - van der Ende, Emma L
AU  - Morenas-Rodriguez, Estrella
AU  - McMillan, Corey
AU  - Grossman, Murray
AU  - Irwin, David
AU  - Sanchez-Valle, Raquel
AU  - Graff, Caroline
AU  - Vandenberghe, Rik
AU  - Pijnenburg, Yolande A L
AU  - Laforce, Robert
AU  - Ber, Isabelle Le
AU  - Lleo, Alberto
AU  - Haass, Christian
AU  - Suarez-Calvet, Marc
AU  - van Swieten, John C
AU  - Seelaar, Harro
TI  - CSF sTREM2 is elevated in a subset in GRN-related frontotemporal dementia.
JO  - Neurobiology of aging
VL  - 103
SN  - 0197-4580
CY  - Amsterdam [u.a.]
PB  - Elsevier Science
M1  - DZNE-2021-00888
SP  - 158.e1 - 158.e5
PY  - 2021
AB  - 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.
KW  - Adult
KW  - Aged
KW  - Biomarkers: cerebrospinal fluid
KW  - C9orf72 Protein: genetics
KW  - Female
KW  - Frontotemporal Dementia: diagnosis
KW  - Frontotemporal Dementia: genetics
KW  - Heterozygote
KW  - Humans
KW  - Male
KW  - Membrane Glycoproteins: cerebrospinal fluid
KW  - Membrane Glycoproteins: metabolism
KW  - Microglia: metabolism
KW  - Microglia: physiology
KW  - Middle Aged
KW  - Mutation
KW  - Progranulins: genetics
KW  - Receptors, Immunologic: metabolism
KW  - Biomarker (Other)
KW  - Cerebrospinal fluid (Other)
KW  - Frontotemporal dementia (Other)
KW  - Microglia (Other)
KW  - sTREM2 (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:33896652
DO  - DOI:10.1016/j.neurobiolaging.2021.02.024
UR  - https://pub.dzne.de/record/155720
ER  -