sTREM2 is associated with amyloid-related p-tau increases and glucose hypermetabolism in Alzheimer's disease.
Level 3 - non-randomized controlled study
Observational cohort study with cross-sectional and longitudinal biomarker analyses
PubMed 36620941 · doi:10.15252/emmm.202216987
What was done
The study examined 402 participants stratified by amyloid-beta (Aβ) status into controls (n = 131), early Aβ-accumulators (CSF Aβ1-42 positive / amyloid-PET negative, n = 70), and late Aβ-accumulators (CSF Aβ1-42 positive / amyloid-PET positive, n = 201). Investigators measured CSF sTREM2, CSF p-tau181, amyloid-PET centiloid, and brain glucose metabolism via FDG-PET to evaluate cross-sectional and longitudinal associations across disease stages.
What was found
In early Aβ-accumulators, higher amyloid-PET centiloid was associated with cross-sectional and longitudinal increases in sTREM2 and p-tau181. Mediation analysis showed that higher sTREM2 mediated the link between centiloid values and p-tau181 increases, and higher sTREM2 correlated with regional FDG-PET hypermetabolism. In late Aβ-accumulators, centiloid was no longer associated with sTREM2, but higher sTREM2 correlated cross-sectionally with higher p-tau181 and FDG-PET hypometabolism. The abstract reports directional associations and subgroup sample sizes but does not report numerical effect sizes, correlation values, or confidence intervals.
Why it matters
The findings delineate a stage-dependent role for TREM2-mediated microglial activation in Alzheimer's disease, suggesting that microglial reactivity begins at the earliest stages of fibrillar Aβ deposition, promotes tau phosphorylation, and transitions from metabolic hyperactivity to hypoactivity as the disease advances.
Limits
The abstract lacks specific statistical metrics, effect sizes, and confidence intervals. Observational biomarker associations cannot establish direct causality, and the early accumulator group was relatively small (n = 70). Follow-up duration and clinical progression endpoints were not reported in the abstract.
Cited by
- supports In the early stages of Alzheimer's disease, affected brain regions show an increase in energy demand and hypermetabolism before progressing to hypometabolism as symptoms emerge.