CSF sTREM2 is elevated in a subset in GRN-related frontotemporal dementia
Por:
van der Ende, EL, Morenas-Rodriguez, E, McMillan, C, Grossman, M, Irwin, D, Sanchez-Valle, R, Graff, C, Vandenberghe, R, Pijnenburg, YAL, Laforce, R, Le Ber, I, Lleo, A, Haass, C, Suarez-Calvet, M, van Swieten, JC, Seelaar, H
Publicada:
1 jul 2021
Ahead of Print:
1 may 2021
Resumen:
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. (C) 2021 The Authors. Published by Elsevier Inc.
Filiaciones:
van der Ende, EL:
Erasmus MC, Alzheimer Ctr Rotterdam, Rotterdam, Netherlands
Erasmus MC, Dept Neurol, Rotterdam, Netherlands
Morenas-Rodriguez, E:
German Ctr Neurodegenerat Dis DZNE Munich, Munich, Germany
Ludwig Maximillians Univ Munchen, Fac Med, Biomed Ctr BMC, Metab Biochem, Munich, Germany
McMillan, C:
Univ Penn, Dept Neurol, Perelman Sch Med, Penn Frontotemporal Degenerat Ctr, Philadelphia, PA 19104 USA
Grossman, M:
Univ Penn, Dept Neurol, Perelman Sch Med, Penn Frontotemporal Degenerat Ctr, Philadelphia, PA 19104 USA
Irwin, D:
Univ Penn, Dept Neurol, Perelman Sch Med, Penn Frontotemporal Degenerat Ctr, Philadelphia, PA 19104 USA
Sanchez-Valle, R:
Univ Barcelona, Hosp Clin Barcelona, Alzheimers Dis & Other Cognit Disorders Unit, IDIBAPS, Barcelona, Spain
Graff, C:
Karolinska Inst, Dept NVS, Div Neurogeriatr, Bioclinicum, Stockholm, Sweden
Karolinska Univ Hosp Solna, Unit Hereditary Dementia, Theme Aging, Stockholm, Sweden
Vandenberghe, R:
Leuven Brain Inst, Dept Neurosci, Lab Cognit Neurol, Leuven, Belgium
Pijnenburg, YAL:
Vrije Univ Amsterdam, Alzheimer Ctr Amsterdam, Dept Neurol, Amsterdam Neurosci, Amsterdam, Netherlands
Laforce, R:
Univ Laval, Dept Sci Neurol, Clin Interdisciplinaire Memoire, CHU Quebec, Quebec City, PQ, Canada
Le Ber, I:
Hop La Pitie Salpetriere, AP HP, Reference Ctr Rare Early Onset Dementias, IM2A,Dept Neurol, Paris, France
Sorbonne Univ, Hop Pitie Salpetriere, AP HP, Paris Brain Inst,Inst Cerveau,ICM,Inserm U1127,CN, Paris, France
Lleo, A:
Hosp Santa Creu & Sant Pau, Neurol Dept, Barcelona, Spain
Haass, C:
German Ctr Neurodegenerat Dis DZNE Munich, Munich, Germany
Ludwig Maximillians Univ Munchen, Fac Med, Biomed Ctr BMC, Metab Biochem, Munich, Germany
Munich Cluster Syst Neurol SyNergy, Munich, Germany
Suarez-Calvet, M:
German Ctr Neurodegenerat Dis DZNE Munich, Munich, Germany
van Swieten, JC:
Erasmus MC, Alzheimer Ctr Rotterdam, Rotterdam, Netherlands
Erasmus MC, Dept Neurol, Rotterdam, Netherlands
Seelaar, H:
Erasmus MC, Alzheimer Ctr Rotterdam, Rotterdam, Netherlands
Erasmus MC, Dept Neurol, Rotterdam, Netherlands
Green Published, hybrid
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