4.5 Article

CSF sTREM2 is elevated in a subset in GRN-related frontotemporal dementia

期刊

NEUROBIOLOGY OF AGING
卷 103, 期 -, 页码 -

出版社

ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2021.02.024

关键词

Frontotemporal dementia; Biomarker; Cerebrospinal fluid; Microglia; sTREM2

资金

  1. Dioraphte Foundation [1402 1300]
  2. European Joint Programme - Neurodegenerative Disease Research (JPND, PreFrontALS)
  3. NIH [AG017586]
  4. Wyncote Foundation
  5. Arking Family Fund
  6. Invetissements d'avenir [ANR11INBS0011]
  7. Swedish Research Council [201502926, 201802754, 201902248]
  8. Swedish Alzheimer's Foundation
  9. Brain Foundation
  10. Demensfonden
  11. Stiftelsen for Gamla Tjanarinnor
  12. Stohnes foundation
  13. Region Stockholm (ALF project)
  14. Schorling FoundationSwedish FTD Initiative
  15. Bluefield Project to Cure Frontotemporal Dementia
  16. Deltaplan Dementie (The Netherlands Organisation for Health Research and Development )
  17. Deltaplan Dementie ( Alzheimer Nederland) [7330550813, 733050103]

向作者/读者索取更多资源

Excessive microglial activation may play a central role in GRN-related frontotemporal dementia. sTREM2 levels were measured in cerebrospinal fluid of presymptomatic and symptomatic GRN and C9orf72 mutation carriers, as well as healthy noncarriers, revealing high levels in a subset of GRN carriers. While sTREM2 is not a promising diagnostic biomarker, it may have potential in monitoring microglial activity and predicting disease progression.
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.

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