The Lancet Neurol: Association of soluble TREM2 with other markers of autosomal dominant Alzheimer's disease and cognitive function

Therapeutic modulation of TREM2-dependent microglial function may provide additional strategies to slow Alzheimer's disease progression
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Although studies in animal models suggest that TREM2 is protective against Alzheimer's disease , its impact on tau pathology and its potential beneficial effects in Alzheimer's disease patients remain unclear

TREM2 is protective against Alzheimer's disease

The aim of this study was to investigate the dynamics of soluble TREM2 (as a biomarker of TREM2 signaling) and amyloid beta (aβ) deposition, taue-related pathology, neuroimaging during autosomal dominant Alzheimer's disease progression Correlations between biological markers and cognitive decline
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Researchers conducted a longitudinal analysis of data from the Dominant Alzheimer's Disease Network (DIAN) observational study, with participants 18 years of age and older recruited between January 1, 2009, and July 31, 2019.
Patients with a family history of dominant Alzheimer's disease were divided into mutation carriers (n=155) and non-carriers (n=93) according to the pathogenic mutations in PSEN1, PSEN2 and APP genes
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Cerebrospinal fluid (CSF) samples from asymptomatic participants were tested for soluble TREM2 every two years

Changes in soluble TREM2 levels during pathogenesis in patients with and without pathogenic variants

In patients with the pathogenic variant, a higher baseline amyloid burden was the only predictor of the annual rate of increase in subsequent increases in soluble TREM2
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In presymptomatic carriers of the pathogenic variant, an increased annual rate of soluble TREM2 was associated with a reduced rate of amyloid deposition

In patients with the pathogenic variant, a higher baseline amyloid load was the only predictor of the annual rate of increase in subsequent increases in soluble TREM2 In patients with the pathogenic variant, a higher baseline amyloid load was The only predictor of the annual rate of increase in subsequent increases in soluble TREM2 in asymptomatic carriers of a pathogenic mutation with an annual rate of increase in soluble TREM2 below the median, the annual rate of increase in p-tau in the CSF correlates with PiB-PET signal There is a correlation between the annual growth rate of p-tau in the CSF and the annual growth rate of PiB-PET signal in asymptomatic carriers of a pathogenic mutation with a below-median annual growth rate of soluble TREM2 There is a certain correlation between

Association of p-tau, t-tau, and PiB-PET with the growth rate of soluble TREM2 in carriers of pathogenic variants

In addition, there was an inverse correlation between cerebrospinal fluid Aβ42 and PiB-PET uptake in pathogenic variant carriers with higher or lower rates of soluble TREM2 growth than the median, assessed longitudinally
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Finally, asymptomatic carriers of the pathogenic variant had increased annual increases in soluble TREM2 with reduced precuneus cortical contraction (r=0.

An inverse correlation exists between CSF Aβ42 and PiB-PET uptake in pathogenic variant carriers with a higher or lower rate of soluble TREM2 than the median pathogenic variant carrier with a higher or lower rate of soluble TREM2 Inverse correlations between cerebrospinal fluid Aβ42 and PiB-PET uptake in variant carriers

Taken together, our findings suggest that in autosomal dominant Alzheimer's disease, TREM2 responses immediately appear in the amyloid cascade following pathological changes in Aβ aggregation , further supporting the role of TREM2 in Aβ plaque deposition and deposition.
role in compaction
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Furthermore, these findings support a beneficial effect of TREM2 on Aβ deposition, Aβ-dependent tau pathology, cortical atrophy, and cognitive decline

In autosomal dominant Alzheimer's disease, the TREM2 response appears in the amyloid cascade immediately following pathological changes in Aβ aggregation In autosomal dominant Alzheimer's disease, once pathological changes in Aβ aggregation occur , the TREM2 response occurs immediately in the amyloid cascade

Original source:

Original source:

Morenas-Rodríguez Estrella,Li Yan,Nuscher Brigitte et al.

Soluble TREM2 in CSF and its association with other biomarkers and cognition in autosomal-dominant Alzheimer's disease: a longitudinal observational studyLeave a comment here