Discovering correlates of off‐target 18F‐MK6240 signal in community‐dwelling adults

Background 18F‐MK6240 binds hyperphosphorylated tau protein in neurofibrillary tangles, a hallmark of Alzheimer’s disease(AD); however, the tracer may also bind to other similarly structured molecules, known as off‐target binding. Off‐target binding is inconsistent across individuals and can lead to biased quantitative assessment, making it difficult to accurately identify neurofibrillary tangle pathology. We examined variable off‐target binding by performing a correlation analysis with demographic factors, vascular risk, lifestyle factors, and co‐morbidities. Method Ninety‐five participants (65±3yrs; 67% women; 42/58% White/Black; 66% Hispanic; 12±4yrs education) in the Northern Manhattan Study of Metabolism and Mind(NOMEM) underwent 18F‐MK6240(90‐110min) and 18F‐Florbetaben(90‐110min) PET imaging and completed surveys, including age, sex, education, exercise levels, and medical history. Only visually‐determined amyloid‐negative participants were included to increase the likelihood that elevated tau PET signal was off‐target. Tau SUVR (cerebellar gray matter reference region) was calculated for composite Braak stages (I/II, III/IV, V/VI) and two known off‐target regions, the choroid plexus and the extra‐cerebral space around the brain. The extra‐cerebral mask was generated by dilating the gray/CSF boundary of the ANTs probability map and then subtracting the brain. Percent of variance explained (r2) from general linear models are reported between off‐target regions and factors of interest. Result Descriptively, 18F‐MK6240 off‐target binding in choroid plexus was positively correlated with SUVR in Braak stage regions I/II (r2 = 0.37;p