Beta‐amyloid plaque accumulation comparison in down syndrome and non‐down syndrome cohorts

Abstract Background Down syndrome (DS) is characterized by earlier beta‐amyloid (Aβ) plaque accumulation and an increased prevalence of Alzheimer’s disease (AD) due to trisomy 21 and triplication of the amyloid precursor protein (APP) gene. While the age of AD onset is earlier in DS, AD pathology progression in non‐DS populations follows similar trends to the DS cohort. This study compares the accumulation rate of Aβ between DS and non‐DS populations measured with [C‐11]PiB at same site using the same scanning procedures. Methods Individuals with at least one Aβ+ [C‐11]PiB scan (Global SUVR>1.40), and at least one Aβ‐ scan from our site at the University of Wisconsin were selected for this study. 12 out of 58 DS participants in the Neurodegeneration in Aging DS (NiAD) study and 14 out of 246 non‐DS subjects from the PREDICT study fit this criteria. All images were collected on an ECAT HR+ scanner from 50‐70 minutes injection (i.d. = 15mCi). Reconstructed PET images were aligned and summed before being normalized into MNI‐152 space and converted into an SUVR image using cerebellar grey matter as a reference region. We determined rate of Aβ accumulation as the change in global SUVR per year, defined as the average of grey matter regions in the anterior cingulate, frontal cortex, parietal cortex, precuneus, temporal cortex, and striatum, and focused on the period when participants became Aβ+. Results Plotting global [C‐11]PiB SUVR and age (Fig 1) there is no age overlap between the two groups. The average rate of amyloid accumulation per year when becoming Aβ+ in the DS group was 0.058±0.026 compared to 0.059±0.028 for the non‐DS sample. The two groups have notably similar mean values, although when organized into box plots (Fig 2), the interquartile range of the DS subjects is 0.044 compared to a tighter 0.019 for non‐DS. Conclusions The pattern of Aβ accumulation in DS and non‐DS groups becoming Aβ+ have similar distributions. While we might expect a higher rate in the DS population due to the additional APP gene, our findings do not support this hypothesis. However, considerable variability in the rate of accumulation is observed requiring further investigation towards understanding this process.