In:
Molecular Neurodegeneration, Springer Science and Business Media LLC, Vol. 15, No. 1 ( 2020-12)
Kurzfassung:
Loss of function of triggering receptor expressed on myeloid cell 2 (TREM2), a key receptor selectively expressed by microglia in the brain, contributes to the development of Alzheimer’s disease (AD). Whether TREM2 levels are pathologically altered during the preclinical phase, and whether cerebrospinal fluid (CSF) soluble TREM2 protein (sTREM2) has a relationship with major pathological processes including Aβ and tau deposition are still unclear. Methods According to the NIA-AA criteria, 659 cognitively normal participants from the Chinese Alzheimer’s Biomarker and LifestylE (CABLE) cohort were divided into four groups, stage 0 (normal Aβ 1–42 , T-tau and P-tau), stage 1 (low Aβ 1–42 , normal T-tau and P-tau), stage 2 (low Aβ 1–42 and high T-tau or P-tau), and suspected non-AD pathology (SNAP) (normal Aβ 1–42 and high T-tau or P-tau), to examine changes of CSF sTREM2 in the preclinical AD. Biomarker cut-off was based on the assumption that one-third of adults with normal cognition have AD pathology. Results The level of CSF sTREM2 in the stage 1 decreased compared with the stage 0 ( P 〈 0.001), and then increased in the stage 2 ( P = 0.008). SNAP individuals also had significantly increased CSF sTREM2 (P 〈 0.001). Results of multiple linear regressions also showed positive correlations of CSF sTREM2 with Aβ 1–42 (β = 0.192, P 〈 0.001), T-tau (β = 0.215, P 〈 0.001) and P-tau (β = 0.123, P 〈 0.001). Conclusion CSF sTREM2 levels are dynamic in preclinical AD. Aβ pathology is associated with a decrease in CSF sTREM2 in the absence of tau deposition and neurodegeneration. However, tau pathology and neurodegeneration are associated with an increase in CSF sTREM2.
Materialart:
Online-Ressource
ISSN:
1750-1326
DOI:
10.1186/s13024-020-00374-8
Sprache:
Englisch
Verlag:
Springer Science and Business Media LLC
Publikationsdatum:
2020
ZDB Id:
2244557-2
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