sTREM2 in discordant CSF Aβ₄₂ and p-tau181

INTRODUCTION: Little is known about the factors underpinning discordant cerebrospinal fluid (CSF) amyloid beta (Aβ)₄₂ versus p-tau181/Aβ₄₂ or CSF Aβ₄₂ versus Aβ positron emission tomography (PET). METHODS: We stratified 570 non-demented Alzheimer's Disease Neuroimaging Initiative (ADNI) participants by Aβ PET and further by CSF Aβ₄₂ or p-tau181/Aβ₄₂. We used analysis of covariance testing adjusting for covariates, followed by Tukey post hoc pairwise comparisons, to compare CSF soluble triggering receptor expressed on myeloid cells-2 (sTREM2) across four participant groups: CSF+ _Aβ42 with CSF− _p-tau/Aβ42, CSF− _Aβ42 with CSF+ _p-tau/Aβ42, and concordant CSF_Aβ42/CSF_p-tau/Aβ42. We also compared sTREM2 across discordant and concordant CSF_Aβ42/PET. RESULTS: Regardless of Aβ PET status, CSF+_Aβ42 with CSF−_p-tau/Aβ42 had lower sTREM2 than CSF−_Aβ42 with CSF+_p-tau/Aβ42. CSF sTREM2 was similarly also associated with discordant CSF Aβ42 /PET. DISCUSSION: Our study suggests the potential roles of sTREM2 in discordant CSF Aβ₄₂ and p-tau181/Aβ₄₂ and discordant CSF_Aβ42/PET. Low- and high-CSF sTREM2 may affect the accuracy of p-tau181/Aβ₄₂ during the clinical work-up of AD. Highlights: 17% of non-demented older adults had discordant CSF Aβ₄₂ versus p-tau181/Aβ₄₂. sTREM2 differed between discordant cases of CSF Aβ₄₂ versus p-tau181/Aβ₄₂. 20% of non-demented older adults had discordant CSF Aβ₄₂ versus Aβ PET. sTREM2 also differed between discordant cases of CSF Aβ₄₂ versus Aβ PET. p-tau181/Aβ₄₂ may miss 6.7% of PET+ non-demented older adults with low sTREM2.