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.
| Original language | English |
|---|---|
| Pages (from-to) | 158.e1-158.e5 |
| Journal | Neurobiology of Aging |
| Volume | 103 |
| DOIs | |
| Publication status | Published - Jul 2021 |
Bibliographical note
Funding Information:This work was supported by 2 Memorabel grants from Deltaplan Dementie (The Netherlands Organisation for Health Research and Development and Alzheimer Nederland; grant numbers 7330550813 and 733050103); The Bluefield Project to Cure Frontotemporal Dementia; the Dioraphte Foundation (grant number 1402 1300); the European Joint Programme ? Neurodegenerative Disease Research (JPND, PreFrontALS); NIH (grant number AG017586); the Wyncote Foundation; Arking Family Fund; Invetissements d'avenir (grant number ANR-11-INBS-0011); the Sch?rling Foundation - Swedish FTD Initiative, Swedish Research Council (2015-02926, 2018-02754, and 2019-02248: JPND GENFI-PROX), Swedish Alzheimer's Foundation, Brain Foundation, Demensfonden, Stiftelsen f?r Gamla Tj?narinnor, Stohnes foundation, and Region Stockholm (ALF project).
Funding Information:
This work was supported by 2 Memorabel grants from Deltaplan Dementie ( The Netherlands Organisation for Health Research and Development and Alzheimer Nederland ; grant numbers 7330550813 and 733050103 ); The Bluefield Project to Cure Frontotemporal Dementia; the Dioraphte Foundation (grant number 1402 1300 ); the European Joint Programme – Neurodegenerative Disease Research (JPND, PreFrontALS); NIH (grant number AG017586 ); the Wyncote Foundation ; Arking Family Fund; Invetissements d'avenir (grant number ANR-11-INBS-0011 ); the Schörling Foundation - Swedish FTD Initiative, Swedish Research Council ( 2015-02926 , 2018-02754 , and 2019-02248 : JPND GENFI-PROX), Swedish Alzheimer's Foundation , Brain Foundation, Demensfonden, Stiftelsen för Gamla Tjänarinnor, Stohnes foundation, and Region Stockholm (ALF project).
Publisher Copyright:
© 2021 The Authors