Tau extent is associated with lower cognition in Down syndrome‐related Alzheimer's disease
- 1University of Wisconsin‐Madison Waisman Center Madison Wisconsin USA
- 2Alzheimer's Therapeutic Research Institute Keck School of Medicine of University of Southern California San Diego California USA
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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BibTeX
@article{zammit2026extent,
title = {{Tau extent is associated with lower cognition in Down syndrome‐related Alzheimer's disease}},
author = {Matthew D. Zammit and Sigan L. Hartley and Bradley T. Christian and Michael S. Rafii},
journal = {Alzheimer's \& Dementia},
year = {2026},
month = oct,
doi = {10.1002/alz.71925},
url = {https://doi.org/10.1002/alz.71925},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Tau extent is associated with lower cognition in Down syndrome‐related Alzheimer's disease
AU - Matthew D. Zammit
AU - Sigan L. Hartley
AU - Bradley T. Christian
AU - Michael S. Rafii
PY - 2026
DA - 2026/10/01
JO - Alzheimer's & Dementia
DO - 10.1002/alz.71925
UR - https://doi.org/10.1002/alz.71925
AB - 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.
SN - 1552-5260
SN - 1552-5279
ER -