Spatial Distribution Of Neurofibrillary Tau With A Beta Load Distinguish Cases Of Cognitive Impairment And Alzheimer'S Disease From Cognitively Stable Individuals With Down Syndrome

218 Background: Adults with Down syndrome (DS) are predisposed to Alzheimer’s disease (AD), with most developing clinical dementia by their late 60s. While Aβ pathology has been previously characterized in this population, its relationship with neurofibrillary tau is much less well understood.\n Objectives: The focus of this study is to determine the associations between global Aβ and regional tau in DS, as well as assess the differences in these biomarkers between cognitively stable adults with DS (CS) and cases of cognitive impairment (MCI/AD).\n Methods: A total of 140 adults with DS (age = 39.3 ± 8.4 years) were evaluated for Aβ and tau using [C-11]PiB and [F-18]AV-1451 PET as part of the ongoing Alzheimer’s Biomarker Consortium-Down Syndrome study (ABC-DS). A consensus on the cognitive status was determined through neuropsychological examination and caregiver report - independent of the PET scans. The MCI/AD group consisted of 13 participants while the CS group contained 117. Cognitive status was unable to be determined for the remaining 10 (excluded from the group analysis). 50-70 minute PiB SUVr and 80-100 minute AV-1451 SUVr images were created using cerebellar gray matter as a reference region. The Amyloid Load index (AβL) was calculated from the PiB SUVr images to determine global Aβ burden. Participants were classified as Aβ(+) if their AβL exceeded 20% (Zammit, 2020). Regional AV-1451 SUVr values were extracted based on ROIs encompassing the six Braak stage regions of tau pathology. Associations between AβL and AV-1451 SUVr in each Braak region were determined using Pearson’s correlations. Differences between AβL and AV-1451 SUVr between the CS and MCI/AD groups were evaluated using the Welch’s t-test.\n Results: Significant positive associations (all p \u003c .00001) were observed between AβL and regional tau for each Braak region (presented as Pearson’s r [95% CI’s]): Braak 1: 0.77 [0.69, 0.83]; Braak 2: 0.78 [0.71, 0.84]; Braak 3: 0.87 [0.82, 0.91]; Braak 4: 0.85 [0.80, 0.89]; Braak 5: 0.84 [0.78, 0.88]; Braak 6: 0.70 [0.61, 0.78] (Figure 1). Significant differences in Aβ and tau burden across all regions (presented as mean ± STD) were observed between the CS and MCI/AD groups (Table 1).\n Conclusions: These findings reveal a highly significant association between global Aβ and regional tau in DS in all six Braak regions, as previously reported in the non-DS population. Additionally, the amount of Aβ and tau deposition (in all six Braak regions) was shown to distinguish cases of MCI/AD from CS individuals with DS.