Advances in Brain Amyloid Imaging.

Abstract

Amyloid-β (Aβ) PET imaging has now been available for over 15 years. The ability to detect Aβ in vivo has greatly improved the clinical and research landscape of Alzheimer's disease (AD) and other neurodegenerative conditions. Aβ imaging provides very reliable, accurate, and reproducible measurements of regional and global Aβ burden in the brain. It has proved invaluable in anti-Aβ therapy trials, and is now recognized as a powerful diagnostic tool. The appropriate use of Aβ PET, when combined with comprehensive clinical evaluation by a dementia-trained specialist, can improve the accuracy of a clinical diagnosis of AD and substantially alter management. It can assist in differentiating AD from other neurodegenerative conditions, often by its ability to rule out the presence of Aβ. When combined with tau imaging, further increase in specificity for the diagnosis of AD can be achieved. The integration of Aβ PET, in conjunction with biomarkers of tau, neurodegeneration and neuroinflammation, into large, longitudinal, observational cohort studies continues to increase our understanding of the development of AD. Its incorporation into clinical trials has been pivotal in defining the most effective anti-Aβ biological therapies and optimal dosing so that effective disease modifying therapy now appears imminent. Aβ deposition is a gradual and protracted process, permitting a wide treatment window for anti-Aβ therapies and Aβ PET has made trials in this preclinical AD period feasible. Continuing improvement in Aβ tracer target to background ratio is allowing trials in earlier AD that tailor drug dosage to Aβ level. The quest to standardize quantification and define universally applicable thresholds for all Aβ tracers has produced the Centiloid method. Centiloid values that correlate well with neuropathologic findings and prognosis have been identified. Rapid cloud-based automated individual scan analysis is now possible and does not require MRI. Challenges remain, particularly around cross camera standardized uptake value ratio variation that need to be addressed. This review will compare available Aβ radiotracers, discuss approaches to quantification, as well as the clinical and research applications of Aβ PET.