CSF sTREM2 is elevated in a subset in GRN-related frontotemporal dementia
van der Ende, Emma L (Alzheimer Center Rotterdam and Dept. of Neurology. Erasmus University Medical Center)
Morenas-Rodriguez, Estrella (Ludwig-Maximilians-Universität München)
McMillan, Corey T. (Penn Frontotemporal Degeneration Center. University of Pennsylvania Perelman School of Medicine)
Grossman, Murray (Penn Frontotemporal Degeneration Center. University of Pennsylvania Perelman School of Medicine)
Irwin, David J. (Penn Frontotemporal Degeneration Center. University of Pennsylvania Perelman School of Medicine)
Sanchez-Valle, Raquel (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Graff, Caroline (Unit of Hereditary Dementia. Theme Aging. Karolinska University Hospital-Solna)
Vandenberghe, Rik (Laboratory for Cognitive Neurology. Department of Neurosciences. Leuven Brain Institute)
Pijnenburg, Yolande (Alzheimer Center Amsterdam. Department of Neurology. Amsterdam Neuroscience. Vrije Universiteit Amsterdam)
Laforce, Robert Jr (Clinique Interdisciplinaire de Mémoire du CHU de Québec. département des Sciences Neurologiques. Université Laval)
Le Ber, Isabelle (Sorbonne Université. Paris Brain Institute. Institut du Cerveau. ICM. Inserm U1127. CNRS UMR 7225. APHP. Hôpital Pitié-Salpêtrière)
Lleó, Alberto (Institut d'Investigació Biomèdica Sant Pau)
Haass, Christian (Munich Cluster for Systems Neurology (SyNergy))
Suárez-Calvet, Marc (German Center for Neurodegenerative Diseases (DZNE) Munich)
van Swieten, John Cornelis (Alzheimer Center Rotterdam and Dept. of Neurology. Erasmus University Medical Center)
Seelaar, Harro (Alzheimer Center Rotterdam and Dept. of Neurology. Erasmus University Medical Center)

Date:	2021
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.
Note:	Altres ajuts: Deltaplan Dementie (The Netherlands Organisation for Health Research and Development and Alzheimer Nederland grant numbers 7330550813, 733050103); Dioraphte Foundation (grant number 1402 1300); the European Joint Programme - Neurodegenerative Disease Research (JPND, PreFrontALS); NIH (grant number AG017586); Wyncote Foundation; Arking Family Fund; Invetissements d'avenir (grant number ANR-11-INBS-0011); Schörling Foundation - Swedish FTD Initiative; Swedish Research Council (2015-02926, 2018-02754, 2019-02248); Swedish Alzheimer's Foundation; Brain Foundation; Demensfonden, Stiftelsen för Gamla Tjänarinnor; Stohnes foundation; Region Stockholm (ALF project).
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Frontotemporal dementia ; Biomarker ; Cerebrospinal fluid ; Microglia ; Strem2
Published in:	Neurobiology of Aging, Vol. 103 (july 2021) , p. 158.e1-158.e5, ISSN 1558-1497

DOI: 10.1016/j.neurobiolaging.2021.02.024
PMID: 33896652

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