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sTREM 2 cerebrospinal fluid levels are a potential biomarker for microglia activity in early ‐ stage Alzheimer's disease and associate with neuronal injury markers

View Article: PubMed Central - PubMed

ABSTRACT

TREM2 is an innate immune receptor expressed on the surface of microglia. Loss‐of‐function mutations of TREM2 are associated with increased risk of Alzheimer's disease (AD). TREM2 is a type‐1 protein with an ectodomain that is proteolytically cleaved and released into the extracellular space as a soluble variant (sTREM2), which can be measured in the cerebrospinal fluid (CSF). In this cross‐sectional multicenter study, we investigated whether CSF levels of sTREM2 are changed during the clinical course of AD, and in cognitively normal individuals with suspected non‐AD pathology (SNAP). CSF sTREM2 levels were higher in mild cognitive impairment due to AD than in all other AD groups and controls. SNAP individuals also had significantly increased CSF sTREM2 compared to controls. Moreover, increased CSF sTREM2 levels were associated with higher CSF total tau and phospho‐tau181P, which are markers of neuronal degeneration and tau pathology. Our data demonstrate that CSF sTREM2 levels are increased in the early symptomatic phase of AD, probably reflecting a corresponding change of the microglia activation status in response to neuronal degeneration.

No MeSH data available.


CSF sTREM2 levels in the different diagnostic groupsScatter plot showing levels of CSF sTREM2 (log‐transformed) in the different diagnostic groups. Red bars represent the mean and the 95% CI. P‐values were assessed by a linear mixed model adjusted by age and gender (fixed effects) and center (random effects).
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emmm201506123-fig-0002: CSF sTREM2 levels in the different diagnostic groupsScatter plot showing levels of CSF sTREM2 (log‐transformed) in the different diagnostic groups. Red bars represent the mean and the 95% CI. P‐values were assessed by a linear mixed model adjusted by age and gender (fixed effects) and center (random effects).

Mentions: CSF sTREM2 differed between diagnostic groups, controlled for age, gender, and center (F3,517 = 4.9, P = 0.002). Levels of CSF sTREM2 were significantly higher in MCI‐AD than in controls (P = 0.002) and AD dementia (P = 0.013) groups. There was a tendency for higher CSF sTREM2 levels in MCI‐AD compared to preclinical AD (P = 0.062). No other group differences were found (Fig 2 and Table 2). In order to confirm the robustness of the results, we also calculated the means and 95% CI of CSF sTREM2 in each diagnostic group based on 1,000 bootstrap samples and the group comparison based on the overlap of the 95% CI confirmed the significant increase of CSF sTREM2 in MCI‐AD compared to the control and AD dementia groups.


sTREM 2 cerebrospinal fluid levels are a potential biomarker for microglia activity in early ‐ stage Alzheimer's disease and associate with neuronal injury markers
CSF sTREM2 levels in the different diagnostic groupsScatter plot showing levels of CSF sTREM2 (log‐transformed) in the different diagnostic groups. Red bars represent the mean and the 95% CI. P‐values were assessed by a linear mixed model adjusted by age and gender (fixed effects) and center (random effects).
© Copyright Policy - creativeCommonsBy
Related In: Results  -  Collection

License
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getmorefigures.php?uid=PMC5120370&req=5

emmm201506123-fig-0002: CSF sTREM2 levels in the different diagnostic groupsScatter plot showing levels of CSF sTREM2 (log‐transformed) in the different diagnostic groups. Red bars represent the mean and the 95% CI. P‐values were assessed by a linear mixed model adjusted by age and gender (fixed effects) and center (random effects).
Mentions: CSF sTREM2 differed between diagnostic groups, controlled for age, gender, and center (F3,517 = 4.9, P = 0.002). Levels of CSF sTREM2 were significantly higher in MCI‐AD than in controls (P = 0.002) and AD dementia (P = 0.013) groups. There was a tendency for higher CSF sTREM2 levels in MCI‐AD compared to preclinical AD (P = 0.062). No other group differences were found (Fig 2 and Table 2). In order to confirm the robustness of the results, we also calculated the means and 95% CI of CSF sTREM2 in each diagnostic group based on 1,000 bootstrap samples and the group comparison based on the overlap of the 95% CI confirmed the significant increase of CSF sTREM2 in MCI‐AD compared to the control and AD dementia groups.

View Article: PubMed Central - PubMed

ABSTRACT

TREM2 is an innate immune receptor expressed on the surface of microglia. Loss‐of‐function mutations of TREM2 are associated with increased risk of Alzheimer's disease (AD). TREM2 is a type‐1 protein with an ectodomain that is proteolytically cleaved and released into the extracellular space as a soluble variant (sTREM2), which can be measured in the cerebrospinal fluid (CSF). In this cross‐sectional multicenter study, we investigated whether CSF levels of sTREM2 are changed during the clinical course of AD, and in cognitively normal individuals with suspected non‐AD pathology (SNAP). CSF sTREM2 levels were higher in mild cognitive impairment due to AD than in all other AD groups and controls. SNAP individuals also had significantly increased CSF sTREM2 compared to controls. Moreover, increased CSF sTREM2 levels were associated with higher CSF total tau and phospho‐tau181P, which are markers of neuronal degeneration and tau pathology. Our data demonstrate that CSF sTREM2 levels are increased in the early symptomatic phase of AD, probably reflecting a corresponding change of the microglia activation status in response to neuronal degeneration.

No MeSH data available.