P4-550: association of plasma-soluble trem2 with neocortical amyloid-β load in cognitively normal elderly participants

Neuroinflammation and activation of innate immunity such as activated microglia are early events in neurodegenerative diseases including Alzheimer's disease (AD). Recently, a rare mutation in the Triggering receptor expressed on myeloid cells 2 (TREM2) gene has been associated with increased risk of late onset AD. Its product of proteolytic processing and shedding, soluble TREM2 (sTREM2), can be measured in the cerebrospinal fluid (CSF) and serum and is a surrogate marker of TREM2-mediated microglia function. CSF and serum sTREM2 have been documented to increase at different clinical stages of AD, however, alterations with respect to Neocortical Amyloid-β Load (NAL) remains unclear. Plasma sTREM2 concentrations were measured employing the sTREM2 Meso Scale Discovery (MSD) assay in participants from the Kerr Anglican Retirement Village Initiative in Ageing Health cohort, aged 65–90 years. Participants underwent a battery of neuropsychological testing to evaluate cognitive performance and were categorized as low NAL (NAL-, n = 65) and high NAL (NAL+, n = 35) as assessed by PET imaging. No significant difference in plasma sTREM2 level was observed between NAL+ and NAL- participants; however, within APOE ε4 carriers, higher NAL was observed in individuals with higher sTREM2 concentrations within quartiles 4 (versus quartile 1). Furthermore, plasma sTREM2 level was positively correlated with NAL within the NAL+ participants only. No significant correlation with cognitive performance. Additionally, plasma sTREM2 was positively correlated with serum kynurenine pathway metabolites (inflammation-related markers).