Older adults with Alzheimer’s disease exhibit an altered relationship between plasma sTREM2 and inflammatory markers

Abstract

AbstractBackgroundAlzheimer’s disease (AD) is the 6th leading cause of death in the US, and currently lacks a blood‐based biomarker for early detection. Triggering receptor expressed on myeloid cells 2 (TREM2) is an immune regulator shown to be protective against AD; a soluble form (sTREM2) circulates in peripheral blood and is a potential indicator of disease progression. Genetic variants of TREM2 are risk factors for AD and other neurodegenerative diseases. Multiple studies also have reported an altered peripheral immune response in AD. However, little is known about the relationship between plasma sTREM2 and the altered peripheral immune response in AD. Our objective was to examine the relationship between sTREM2 and inflammatory markers in a spectrum of older adults including cognitively normal (CN) controls, amnestic mild cognitive impairment (MCI) and AD. The hypothesis of this exploratory study was that TREM2‐related inflammatory activity is a stage specific (MCI or AD dementia) biomarker of AD.MethodStages of AD progression were characterized based on symptoms, designated in our study as CN controls, MCI, and AD. Alternatively, CSF amyloid beta, phosphorylated tau and total tau were measured, as described by the NIA‐AA Research Framework “ATN continuum”. Our study aims were to (1) define the relationship between sTREM2‐related inflammatory activity and AD clinical diagnosis, and (2) characterize sTREM2‐related inflammatory activity within the ATN continuum. Plasma sTREM2 and 38 cytokines were measured using the Luminex platform.ResultWe investigated this hypothesis in an exploratory cohort of CN, MCI, and AD subjects. We observed differential plasma sTREM2 and cytokines levels, correlations, and patterns across both AD groups defined by symptoms and the ATN continuum. This suggests the existence of alteration in normal peripheral sTREM2‐related inflammatory activity along AD and ATN stages.ConclusionThese data provide important support to the hypothesis that TREM2‐related inflammatory activity is a stage specific biomarker of AD progression. Our results provides the groundwork for future functional investigation and therapeutic strategy research.