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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.


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CSF sTREM2 levels in cognitively normal SNAPs and in MCI‐noADScatter plot showing CSF sTREM2 levels across different groups of cognitively normal individuals: SNAP, suspected non‐AD pathophysiology (n = 39); control subjects (n = 150); and preclinical AD (n = 63).Differences in CSF sTREM2 in MCI‐AD (n = 111) compared to MCI‐noAD (n = 103) and controls (n = 150).Data information: The red bars represent the mean and the 95% CI. P‐values were assessed by a linear mixed‐effects model adjusting by age and gender (fixed effects) and center (random effect).
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emmm201506123-fig-0004: CSF sTREM2 levels in cognitively normal SNAPs and in MCI‐noADScatter plot showing CSF sTREM2 levels across different groups of cognitively normal individuals: SNAP, suspected non‐AD pathophysiology (n = 39); control subjects (n = 150); and preclinical AD (n = 63).Differences in CSF sTREM2 in MCI‐AD (n = 111) compared to MCI‐noAD (n = 103) and controls (n = 150).Data information: The red bars represent the mean and the 95% CI. P‐values were assessed by a linear mixed‐effects model adjusting by age and gender (fixed effects) and center (random effect).

Mentions: As a secondary aim, we studied CSF samples from cognitively normal individuals with SNAP (n = 39), that is, individuals with abnormal neurodegeneration biomarkers (T‐tau and/or P‐tau181P) without the presence of significant amyloid pathology (as measured by abnormally decreased Aβ1–42) (Jack et al, 2012). We compared them with the rest of cognitively normal individuals, namely controls and preclinical AD group. Interestingly, we found that CSF sTREM2 levels differed between groups (F2,242 = 7.5, P = 0.0007) and were particularly increased in the SNAP group compared to the control (P = 0.0004) and the preclinical AD group (P = 0.024) (Fig 4A). These findings may indicate that an increase in CSF sTREM2 levels in response to neuronal injury (as measured by CSF tau levels) can occur without amyloidosis.


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 cognitively normal SNAPs and in MCI‐noADScatter plot showing CSF sTREM2 levels across different groups of cognitively normal individuals: SNAP, suspected non‐AD pathophysiology (n = 39); control subjects (n = 150); and preclinical AD (n = 63).Differences in CSF sTREM2 in MCI‐AD (n = 111) compared to MCI‐noAD (n = 103) and controls (n = 150).Data information: The red bars represent the mean and the 95% CI. P‐values were assessed by a linear mixed‐effects model adjusting by age and gender (fixed effects) and center (random effect).
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Related In: Results  -  Collection

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emmm201506123-fig-0004: CSF sTREM2 levels in cognitively normal SNAPs and in MCI‐noADScatter plot showing CSF sTREM2 levels across different groups of cognitively normal individuals: SNAP, suspected non‐AD pathophysiology (n = 39); control subjects (n = 150); and preclinical AD (n = 63).Differences in CSF sTREM2 in MCI‐AD (n = 111) compared to MCI‐noAD (n = 103) and controls (n = 150).Data information: The red bars represent the mean and the 95% CI. P‐values were assessed by a linear mixed‐effects model adjusting by age and gender (fixed effects) and center (random effect).
Mentions: As a secondary aim, we studied CSF samples from cognitively normal individuals with SNAP (n = 39), that is, individuals with abnormal neurodegeneration biomarkers (T‐tau and/or P‐tau181P) without the presence of significant amyloid pathology (as measured by abnormally decreased Aβ1–42) (Jack et al, 2012). We compared them with the rest of cognitively normal individuals, namely controls and preclinical AD group. Interestingly, we found that CSF sTREM2 levels differed between groups (F2,242 = 7.5, P = 0.0007) and were particularly increased in the SNAP group compared to the control (P = 0.0004) and the preclinical AD group (P = 0.024) (Fig 4A). These findings may indicate that an increase in CSF sTREM2 levels in response to neuronal injury (as measured by CSF tau levels) can occur without amyloidosis.

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