TY - JOUR T1 - Neurofibrillary tau emerges in adults with Down syndrome during the earliest stages of Aβ accumulation JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 42 LP - 42 VL - 62 IS - supplement 1 AU - Matthew Zammit AU - Alexandra DiFilippo AU - Tyler Tullis AU - Andrew McVea AU - Dana Tudorascu AU - Charles Laymon AU - Ann Cohen AU - Shahid Zaman AU - Beau Ances AU - Sigan Hartley AU - Sterling Johnson AU - Charles Stone AU - Chester Mathis AU - William Klunk AU - Benjamin Handen AU - Bradley Christian Y1 - 2021/05/01 UR - http://jnm.snmjournals.org/content/62/supplement_1/42.abstract N2 - 42Introduction: Adults with Down syndrome (DS) are genetically predisposed to Alzheimer’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’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’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. ER -