Amyloid Load: A More Sensitive Biomarker for Amyloid Imaging

Abstract

Amyloid-β (Aβ) plays a key role in the pathogenesis of Alzheimer disease (AD) and can be imaged in vivo using 18 F-florbetapir PET. A composite SUV ratio (SUVr) is a commonly used outcome measure for quantifying the global Aβ burden; however, sensitivity is suboptimal and can lead to low power in clinical trials. We introduce amyloid load, Aβ L , as a novel biomarker to quantify the global Aβ burden along with an automated algorithm for its calculation (Amyloid IQ). Aβ L is evaluated on cross-sectional and longitudinal data obtained from the Alzheimer's Disease Neuroimaging Initiative. The cross-sectional data consisted of 769 subjects across the disease spectrum (211 healthy controls, 223 patients with early mild cognitive impairment, 204 with late mild cognitive impairment, and 132 with AD). The distributions of Aβ L in the 4 different classifications were compared, and the same analyses were applied to a composite SUVr outcome measure. The effect sizes (Hedges g) between all but one classification were higher for Aβ L than for composite SUVr, with the mean difference being 46%. Of the patients with early mild cognitive impairment, 147 had a 2-y follow-up scan, and the effect size between baseline and follow-up for Aβ L was 0.49, compared with 0.36 for a composite SUVr, demonstrating an equivalent increase in power for longitudinal data. These results offer evidence that Aβ L will be a valuable outcome measure in future Aβ imaging studies, providing a substantial increase in power over currently used SUVr methods.

Amyloid accumulation in Down syndrome measured with amyloid load

“…Both global and regional PiB SUVrs have been used to distinguish Aβ‐positivity in preclinical AD, 33 and demonstrated to detect increases in Aβ signal over time in DS 29,30 . Although SUVr is used routinely to track changes in Aβ burden for longitudinal studies, it can be prone to high variability during assessment of longitudinal Aβ change, 34,35 resulting in lower power to detect biological significance from the data 1 …”

“…The metric of amyloid load ( Aβ L ) was developed as a global (ie, whole brain) outcome measure to reduce variability by utilizing template‐based images of Aβ‐specific and non‐specific radioligand uptake 1 . Proper voxel‐based weighting of these images can then be used to provide a global estimate of Aβ L .…”

Improving PET Imaging Acquisition and Analysis With Machine Learning: A Narrative Review With Focus on Alzheimer's Disease and Oncology

“…An equivalent increase in effect size was found for longitudinal data, assessing patients who had a follow-up PET scan after 2 years. 50 The authors envision that providing expert knowledge as commercially available software would allow clinical trials to run more efficiently by decreasing trial size, timelines, and cost.…”

An improved preparation of [18F]AV‐45 by simplified solid‐phase extraction purification

“…Florbetapir f18 PET imaging study is now being used to determine the presence of amyloid load in the brain as a significant risk factor for developing AD. Amyloid‐β plaques in the brain are associated with mild cognitive impairment or dementia of uncertain etiology . The original method for preparing [ 18 F]AV‐45 ([ 18 F] 5 ) was based on the final HPLC purification .…”

“…Amyloidβ plaques in the brain are associated with mild cognitive impairment or dementia of uncertain etiology. 11,12 The original method for preparing [ 18 F]AV-45 ([ 18 F]5) was based on the final HPLC purification. 13,14 Similar to the [ 18 F]FDG production described above, we previously reported an effort to streamline the [ 18 F]AV-45 ([ 18 F]5) production.…”