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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.


Related in: MedlinePlus

CSF sTREM2 is associated with ageScatter plot representing CSF sTREM2 as a function of age in the different diagnostic groups. Solid lines indicate the linear regression for each of the groups; the dashed line indicates the linear regression within the entire sample. P‐values were assessed by Pearson product‐moment correlations..
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emmm201506123-fig-0001: CSF sTREM2 is associated with ageScatter plot representing CSF sTREM2 as a function of age in the different diagnostic groups. Solid lines indicate the linear regression for each of the groups; the dashed line indicates the linear regression within the entire sample. P‐values were assessed by Pearson product‐moment correlations..

Mentions: Age was positively correlated with CSF sTREM2 in the pooled group of subjects (Pearson r = +0.391, P < 0.0001). The correlation was still significant when tested within each diagnostic group, including the control group (Pearson r = +0.177, P = 0.030), preclinical AD (Pearson r = +0.510, P < 0.0001), MCI‐AD (Pearson r = +0.289, P = 0.002), and AD dementia (Pearson r = +0.310, P < 0.0001) (Fig 1). Levels of CSF sTREM2 were not significantly affected by gender (F1,521 = 0.1, P = 0.719) nor by APOE ε4 status (F1,377 = 0.4, P = 0.552), controlled by age and center, when tested within the entire sample or each diagnostic group.


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 is associated with ageScatter plot representing CSF sTREM2 as a function of age in the different diagnostic groups. Solid lines indicate the linear regression for each of the groups; the dashed line indicates the linear regression within the entire sample. P‐values were assessed by Pearson product‐moment correlations..
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Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC5120370&req=5

emmm201506123-fig-0001: CSF sTREM2 is associated with ageScatter plot representing CSF sTREM2 as a function of age in the different diagnostic groups. Solid lines indicate the linear regression for each of the groups; the dashed line indicates the linear regression within the entire sample. P‐values were assessed by Pearson product‐moment correlations..
Mentions: Age was positively correlated with CSF sTREM2 in the pooled group of subjects (Pearson r = +0.391, P < 0.0001). The correlation was still significant when tested within each diagnostic group, including the control group (Pearson r = +0.177, P = 0.030), preclinical AD (Pearson r = +0.510, P < 0.0001), MCI‐AD (Pearson r = +0.289, P = 0.002), and AD dementia (Pearson r = +0.310, P < 0.0001) (Fig 1). Levels of CSF sTREM2 were not significantly affected by gender (F1,521 = 0.1, P = 0.719) nor by APOE ε4 status (F1,377 = 0.4, P = 0.552), controlled by age and center, when tested within the entire sample or each diagnostic group.

View Article: PubMed Central - PubMed

ABSTRACT

TREM2 is an innate immune receptor expressed on the surface of microglia. Loss&#8208;of&#8208;function mutations of TREM2 are associated with increased risk of Alzheimer's disease (AD). TREM2 is a type&#8208;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&#8208;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&#8208;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&#8208;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.


Related in: MedlinePlus