Plasma soluble TREM2 and its association with other biomarkers in cognitively normal older adults at risk of Alzheimer's disease — The Association Specialists
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Plasma soluble TREM2 and its association with other biomarkers in cognitively normal older adults at risk of Alzheimer's disease (22032)

Prita Asih 1 , Cameron Morris 2 , Wang Hong 2 , Steve Pedrini 3 , Kathryn Goozee 1 , Kevin Taddei 3 , Hamid Sohrabi 4 , Simon Laws 3 , Stephanie Rainey-Smith 4 , Pratishtha Chatterjee 5 , Ralph Martins 1 3
  1. Macquarie University, Macquarie Park, NSW, Australia
  2. Eli Lilly and Company, Indianapolis, IN, USA
  3. Edith Cowan University, Perth, WA, Australia
  4. Murdoch University, Perth, WA, Australia
  5. The Florey Institute, Melbourne, Victoria, Australia

Objective: Investigate the association of plasma sTREM2 levels with Neocortical Amyloid-β Load (NAL) and other AD biomarkers in cognitively normal elderly at risk of AD (high NAL) compared to those with low NAL. Also, to investigate the effect of AD-linked TREM2 variants on plasma sTREM2 levels and preclinical AD features.

Methods: Plasma sTREM2 concentrations were measured employing the Meso Scale Discovery (MSD) assay in the KARVIAH cohort, aged 65–90 years. Genetic data, levels of microglial serum kynurenine pathway (KP) metabolites, plasma GFAP, total tau, phosphorylated tau, and NFL were included for correlation analysis. Based on NAL SUVR (low NAL (n = 65) and high NAL (n = 35), clinical plasma sTREM2 levels, APOE and TREM2 genotypes, subgroup analysis was carried out. Results: No significant difference in plasma sTREM2 was observed between high NAL and low NAL participants; however, among APOE ε4 carriers, higher NAL levels were observed in individuals with higher sTREM2 concentrations. Furthermore, plasma sTREM2 positively correlated with NAL and plasma NFL in high NAL participants only. Additionally, plasma sTREM2 positively correlated with plasma KP metabolites, pTau181, and pTau231, albeit independently of NAL status. Interestingly, plasma sTREM2 in high NAL with R47H carriers positively correlated with NAL and negatively with cognitive performance.

Conclusions: Plasma sTREM2 is closely associated with amyloid-β positivity, neuroinflammation, and tau-induced neurodegeneration in cognitively normal older adults at risk of AD. This study also unveiled a critical genetic association between APOE and TREM2 which may synergistically affect brain amyloid-β load at the early stage of AD.