Amyloid accumulation in Down syndrome measured with amyloid load

Abstract

Introduction Individuals with Down syndrome (DS) show enhanced amyloid beta (Aβ) deposition in the brain. A new positron emission tomography (PET) index of amyloid load (AβL) was recently developed as an alternative to standardized uptake value ratios (SUVrs) to quantify Aβ burden with high sensitivity for detecting and tracking Aβ change.1 Methods AβL was calculated in a DS cohort (N = 169, mean age ± SD = 39.6 ± 8.7 years) using [C‐11]Pittsburgh compound B (PiB) PET imaging. DS‐specific PiB templates were created for Aβ carrying capacity (K) and non‐specific binding (NS). Results The highest values of Aβ carrying capacity were found in the striatum and precuneus. Longitudinal changes in AβL displayed less variability when compared to SUVrs. Discussion These results highlight the utility of AβL for characterizing Aβ deposition in DS. Rates of Aβ accumulation in DS were found to be similar to that observed in late‐onset Alzheimer's disease (AD; ≈3% to 4% per year), suggesting that AD progression in DS is of earlier onset but not accelerated.

Patterns of glucose hypometabolism in Down syndrome resemble sporadic Alzheimer's disease except for the putamen

“…While regional PiB SUVR was able to distinguish FDG change across Aβ+ and Aβ– groups, the global Aβ L measure displayed larger effect sizes and may be a more sensitive metric to predict FDG change. Previous studies have shown that the Aβ L metric improves quantification due to its suppression of nonspecific radioligand binding signal, resulting in greater sensitivity to detect small increases in Aβ 63,64 . This improved sensitivity to measure Aβ with Aβ L may translate to a more sensitive prediction of FDG change during the early stages of AD progression.…”

“…Standardized uptake value ratio (SUVR) images were generated by voxel normalization to cerebellar gray matter (PiB) or a cerebral global mean (FDG). Global Aβ was calculated from the PiB SUVR images using the Aβ L index following methodology specific to DS brains 64 . Regional values of SUVR were calculated for PiB and FDG in early‐stage AD regions (parietal cortex, precuneus/posterior cingulate), late‐stage regions (frontal cortex, temporal cortex, anterior cingulate), the caudate, and putamen.…”

Neurofibrillary tau depositions emerge with subthreshold cerebral beta-amyloidosis in down syndrome

“…This striatum-first pattern of Aβ deposition in Down syndrome is consistent with the observations in individuals with autosomal-dominant Alzheimer’s disease and APP duplication ( Bateman et al, 2012 , Klunk et al, 2007 , Remes et al, 2008 , Villemagne et al, 2009 ). Similar to late-onset Alzheimer’s disease, Down syndrome presents identical patterns of cortical Aβ retention ( Annus et al, 2016 , Cole et al, 2017 , Hartley et al, 2014 , Jennings et al, 2015 , Landt et al, 2011 , Lao et al, 2018 , Lao et al, 2016 , Mak et al, 2019 , Matthews et al, 2016 , Rafii et al, 2015 , Rafii et al, 2017 , Sabbagh et al, 2015 ) and shows longitudinal increases of ~3–4% per year, however with a wide variation in the age of Aβ onset ( Lao et al, 2017 , Tudorascu et al, 2019 , Zammit et al, 2020 ). In late-onset Alzheimer’s disease, striatal Aβ retention is observed much later in the disease progression ( Hanseeuw et al, 2018 ) compared to Down syndrome, indicating that the striatum can be used as an early marker of Alzheimer’s disease progression in this population ( Cohen et al, 2018 ).…”

Basal Forebrain Cholinergic Neurons: Linking Down Syndrome and Alzheimer’s Disease

“…With PET imaging, a pattern of early and prominent amyloid-β retention was identified in the dorsal and ventral striatum ( Handen et al, 2012 ); a pattern which has also been observed in other forms of early-onset AD ( Klunk et al, 2007 ; Remes et al, 2008 ; Villemagne et al, 2009 ; Bateman et al, 2012 ). Apart from the striatum, the cortical retention of amyloid-β in DS has an identical pattern to late-onset AD, with amyloid-β increasing at longitudinal rates of 3–4% annually ( Lao et al, 2017 ; Tudorascu et al, 2019 ; Zammit et al, 2020a , 2021 ).…”