@article {Zammit42, author = {Matthew Zammit and Alexandra DiFilippo and Tyler Tullis and Andrew McVea and Dana Tudorascu and Charles Laymon and Ann Cohen and Shahid Zaman and Beau Ances and Sigan Hartley and Sterling Johnson and Charles Stone and Chester Mathis and William Klunk and Benjamin Handen and Bradley Christian}, title = {Neurofibrillary tau emerges in adults with Down syndrome during the earliest stages of Aβ accumulation}, volume = {62}, number = {supplement 1}, pages = {42--42}, year = {2021}, publisher = {Society of Nuclear Medicine}, abstract = {42Introduction: Adults with Down syndrome (DS) are genetically predisposed to Alzheimer{\textquoteright}s disease (AD) and accumulate beta-amyloid plaques (Aβ) early in life. The aim of this study was to evaluate neurofibrillary tau deposition in DS adults that are classified as PET amyloid-negative (A-). Methods: A total of 130 A- adults with DS (mean age: 36.5 [6.77] years) and 40 healthy, non-DS sibling controls (43.2 [12.6] years) underwent T1w-MRI, [C-11]PiB and [F-18]AV-1451 PET scans. MRI images were processed using FreeSurfer v5.3.0 to generate ROI masks encompassing the Braak staging of tau pathology. PiB and AV-1451 SUVr images were generated using a cerebellar gray matter reference region. Global Aβ burden was calculated using the amyloid load metric (AβL). Regional tau was assessed using AV-1451 SUVr Z-scores relative to the control group. Partial volume correction was performed on AV-1451 SUVrs in the Braak I-II regions using the geometric transfer matrix method. N=26 DS adults had elevated Aβ at typical subthreshold detection levels (13.3 \< AβL \< 20) and were re-classified as subthreshold A+. AV-1451 images were averaged for the A- and subthreshold A+ groups, and the difference was taken between the two groups to generate a ΔSUVr image. Braak regional SUVr Z-scores were then compared across the two groups using Student{\textquoteright}s t-tests while adjusting for imaging site. The analysis was then repeated using an age-matched sample of A- (N=68) and subthreshold A+ (N=26) DS. Results: The SUVr difference image revealed higher AV-1451 uptake in Braak regions I-III for the subthreshold A+ group (Figure 1). Student{\textquoteright}s t-tests revealed significantly higher AV-1451 uptake in Braak regions I-III for the subthreshold A+ group (Table 1). No difference in AV-1451 uptake was observed between groups in Braak regions IV-VI (Table 1). Higher AV-1451 uptake in Braak regions I-III was also observed in the subthreshold A+ group when compared to the age-matched A- group (Table 2). Discussion: These results show that subthreshold Aβ in DS is accompanied by elevated tau in the early Braak stage regions. These findings indicate that there is a short latency between the onset of Aβ and the spread of neurofibrillary tau in DS.}, issn = {0161-5505}, URL = {https://jnm.snmjournals.org/content/62/supplement_1/42}, eprint = {https://jnm.snmjournals.org/content}, journal = {Journal of Nuclear Medicine} }