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iNature
Soluble trigger receptors expressed on myeloid cell 2 (TREM2) play an important role
in the clearance of pathological amyloid β (Aβ) in Alzheimer's disease (AD).
On December 15, 2022, Liu Jun, Deng Yulei and Li Yuanyuan of Shanghai Jiao Tong University jointly published a joint newsletter entitled "Soluble TREM2 levels associate with conversion from mild cognitive impairment to" online in the Journal of Clinical Investigation (IF=19).
Alzheimer's disease", which showed that soluble TREM2 levels were associated
with the transition from mild cognitive impairment to Alzheimer's disease.
The results showed that patients with MCI with low levels of CSF sTREM2 and Aβ1-42 were more likely to develop AD
.
In participants with positive Aβ deposition, elevated CSF sTREM2 levels were associated with
a reduced risk of MCI conversion to AD as assessed by AV45 imaging.
Meanwhile, in the NRHAD cohort, individuals with high plasma levels of sTREM2 in the MCI group were at greater risk of developing AD, while lowAβ1-42 with high plasma levels of sTREM2 was associated with
faster cognitive decline.
In addition, CSF sTREM2 levels were highly correlated
with plasma sTREM2 levels in the CABLE database.
These findings suggest that sTREM2 may be a potential predictive biomarker for MCI-AD conversion
.
in regulating microglia phagocytosis and response to inflammatory stimuli.
The extracellular domain of TREM2 cleaves to soluble TREM2 (sTREM2) and releases into cerebrospinal fluid (CSF) and is considered an indicator
of microglial activity.
In Alzheimer's disease (AD), microglia are critical for the recognition and clearance of pathological amyloid β (Aβ), while sTREM2 mediates the response of various microglia to Aβ during neurodegeneration and regulates microglia-plaque interactions
.
Studies in AD animal models confirmed that sTREM2 plays a protective role
in Aβ pathology in AD models.
However, clinical studies on the relationship between sTREM2 and Aβ have not been consistent
.
One study showed that sTREM2 levels correlated
with Aβ1-42 levels in the cerebrospinal fluid of patients with mild cognitive impairment (MCI).
Conversely, other studies have reported that in AD, CSF sTREM2 levels are associated with CSF Tau rather than Aβ1-42 levels
.
Therefore, in-depth studies are needed to elucidate the clinical significance
of sTREM2 as a potential central and peripheral biomarker for AD.
Correlation between CSF and plasma sTREM2 levels in the CABLE cohort (Image from Journal of Clinical Investigation) In addition, a recent study showed that the proportion of sTREM2 and phosphorylated Tau (sTREM2/p-Tau) in CSF was associated
with cognitive decline 。 Previous studies have shown that sTREM2 concentrations change dynamically during AD progression and peak in the early symptom phase, suggesting that an early increase in CSF sTREM2 can be used to predict MCI-to-AD conversion
.
Although multiple studies have shown that higher levels of TREM2 mRNA in peripheral blood correlate with MCI-AD conversion, the predictive power of plasma sTREM2 in peripheral blood has not been fully studied
.
Therefore, the study first investigated changes in CSF sTREM2 concentrations
in different subgroups in the ADNI database classified according to CSF Aβ1-42 levels and 18F-labeledradioligand PET imaging (AV45) results in a cross-sectional longitudinal cohort study 。 In addition, to explore the potential role of peripheral blood sTREM2 in MCI-AD transformation, the study examined whether plasma sTREM2 could predict cognitive decline in patients with MCI and evaluated the presence of
amyloid pathology in the authors' clinical cohort.
The study suggests that soluble TREM2 levels are associated
with the transition from mild cognitive impairment to Alzheimer's disease.
The results showed that patients with MCI with low levels of CSF sTREM2 and Aβ1-42 were more likely to develop AD
.
In participants with positive Aβ deposition, elevated CSF sTREM2 levels were associated with
a reduced risk of MCI conversion to AD as assessed by AV45 imaging.
Meanwhile, in the NRHAD cohort, individuals with high plasma levels of sTREM2 in the MCI group were at greater risk of developing AD, while low Aβ1-42 with high plasma levels of sTREM2 was associated with
faster cognitive decline.
In addition, CSF sTREM2 levels were highly correlated
with plasma sTREM2 levels in the CABLE database.
These findings suggest that sTREM2 may be a potential predictive biomarker for MCI-AD conversion
.
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The content is [iNature]
