BEST IN PHYSICS (RADIOPHARMACEUTICALS): Early Detection of Alzheimer’s Disease Tau Accumulation Measured with [¹⁸F]AV1451 PET at Low Levels of Amyloid Burden In Adults with Down Syndrome
Abstract
Purpose
Alzheimer’s disease (AD) progression can be monitored with longitudinal PET imaging. Changes in amyloid and tau; two characteristic AD proteins, are measured using [11C]PiB and [18F]AV1451, similar to how serial imaging with [18F]FDG is used to clinically assess disease progression and treatment response. Adults with Down syndrome (DS) are genetically predisposed to AD resulting in an accelerated disease timeline with a shortened latency period between amyloid and tau emergence. This work examines whether PET longitudinal changes in tau deposition measured with [¹⁸F]AV1451 are detectable at low levels of amyloid burden in adults with DS.
Methods
131 DS participants with ≥1 paired [¹¹C]PiB amyloid and [18F]AV1451 tau scans were recruited from the Alzheimer Biomarkers Consortium - Down Syndrome (ABC-DS) study. Amyloid burden was measured in Centiloids (CL), with early amyloid positivity defined by elevated striatum uptake (Aβ+: SUVr > 1.07). Tau burden was measured in the mesial temporal region. Longitudinal trajectories of individuals with CL<33 were grouped by Aβ status and aligned by an individual’s first tau observation. Individuals with CL<18 were evaluated cross-sectionally for elevated tau burden in Aβ+ and Aβ- groups.
Results
Longitudinal trajectories demonstrated increasing tau accumulation in Aβ+ individuals at a rate of 0.03 SUVr/year, whereas no significant tau accumulation was observed in participants who remained Aβ-. Cross-sectional analyses demonstrated elevated tau burden at low amyloid levels, indicating tau emergence prior to PET-measurable cortical amyloid burden in DS.
Conclusion
Early tau accumulation is detectable with [18F]AV1451 stratified at low levels of amyloid burden in adults with DS. Characterizing tau emergence, which is strongly correlated with cognitive decline, will help clinical trials evaluate whether disease-modifying therapies are effective at altering tau progression in DS.