CSF sTREM2 in deliriumrelation to Alzheimer's disease CSF biomarkers Aβ42, t-tau and p-tau

BackgroundDelirium and dementia share symptoms of cognitive dysfunctions, and mechanisms of neuroinflammation appear involved in both conditions. Triggering receptor expressed on myeloid cells 2 (TREM2) is linked to dementia and neurodegenerative disease. It encodes expression of an innate immune receptor in the brain expressed by microglia. The level of the soluble fragment of TREM2 (sTREM2) is reported to increase in the cerebrospinal fluid (CSF) already in prodromal and asymptomatic Alzheimer's disease.MethodsWe analyzed the level of CSF sTREM2 in relation to delirium and dementia. The study included patients with or without pre-existing dementia who underwent acute hip fracture surgery (n=120), and some of the patients developed delirium (n=65). A medical delirium cohort (n=26) was also examined. ELISA was used to determine the level of sTREM2 in CSF.ResultsDelirium was associated with a higher level of CSF sTREM2 only among those without pre-existing dementia (p=0.046, n=15, n=44), particularly among patients developing delirium after CSF sampling (p=0.02, n=7, n=44). Between patients with dementia, there was no group difference, but the CSF sTREM2 level increased with waiting time for surgery (r(S)=0.39, p=0.002, n=60) and correlated well with the CSF Alzheimer's disease biomarkers, A42, and t-tau/p-tau (r(S)=0.40, p=0.002, r(S)=0.46, p<0.001/ r(S)=0.49, p<0.001, n=60). Among patients with dementia, the level of A38 and A40 also correlated positively with sTREM2 in CSF (A38(MSD)r(S)=0.44, p=0.001; A40(MSD)r(S)=0.48, p<0.001; A42(MSD)r(S)=0.43, p<0.001, n=60).ConclusionThe findings reinforce the involvement of neuroinflammation in delirium, yet with separate responses in patients with or without pre-existing dementia. Our findings support the concept of primed microglia in neurodegenerative disease and central immune activation after a peripheral trauma in such patients. A CSF biomarker panel of neuroinflammation might be valuable to prevent delirium by identifying patients at risk.