Abstract
INTRODUCTION
18F-MK6240 is a second-generation tau positron emission tomography (PET) tracer with high dynamic range able to detect early tau pathology in Alzheimer’s disease, however, its binding characteristics have not been evaluated in Down syndrome (DS), which is a population at high risk for early Alzheimer’s disease onset. Past Down DS tau PET studies used 18F-Flortaucipir, which suffers from off-target binding in early-stage regions, limiting pathology confirmation. This study evaluates the binding of 18F-MK6240 in DS and examines the relationship between tau extent and cognition.
METHODS
Tau Extent was measured in participants from the Trial Ready Cohort-Down Syndrome using 18F-MK6240 and from the Alzheimer Alzheimer’s Biomarker Consortium—Down Syndrome using 18F-Flortaucipir. Data were compared, harmonized, and explored in relationship to cognitive endpoints with consideration of age, sex, apolipoprotein E (APOE) ε4 status, and level of intellectual disability.
RESULTS
18F-MK6240 showed binding in the mesial temporal lobe shortly following the onset of beta-amyloid plaques, similar to our observations with 18F-Flortaucipir. Increased tau extent correlated with lower episodic memory and overall cognitive performance scores. Age, intellectual disability level, and sex also influenced cognitive scores.
DISCUSSION
This first evaluation of 18F-MK6240 in DS demonstrates its suitability as a sensitive biomarker for Alzheimer’s disease tau pathology. Furthermore, the inverse associations between Tau Extent as measured by both 18F-MK6240 and 18F-Flortaucipir and cognitive outcomes highlight the potential of these biomarkers to evaluate signs of early cognitive change, underscoring the urgent need to include this population in early clinical interventions.
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This post is Copyright: | October 25, 2026
Neuro-Dementia