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
- Dioraphte Foundation [1402 1300]
- European Joint Programme - Neurodegenerative Disease Research (JPND, PreFrontALS)
- NIH [AG017586]
- Wyncote Foundation
- Arking Family Fund
- Invetissements d'avenir [ANR11INBS0011]
- Swedish Research Council [201502926, 201802754, 201902248]
- Swedish Alzheimer's Foundation
- Brain Foundation
- Demensfonden
- Stiftelsen for Gamla Tjanarinnor
- Stohnes foundation
- Region Stockholm (ALF project)
- Schorling FoundationSwedish FTD Initiative
- Bluefield Project to Cure Frontotemporal Dementia
- Deltaplan Dementie (The Netherlands Organisation for Health Research and Development )
- Deltaplan Dementie ( Alzheimer Nederland) [7330550813, 733050103]
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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