Aβ Imaging: feasible, pertinent, and vital to progress in Alzheimer’s disease

Abstract

We acknowledge that there are a number of caveats with regard to the clinical value of Aβ imaging. This includes disorders other than AD which may show Aβ deposition (such as dementia with Lewy bodies), the unknown time to conversion in healthy Aβ-positive persons or the relative plateauing of the Aβ burden in later stages of disease [79, 87–90]. However, these caveats are not related to the proven functionality of the tracers and should not hamper the application and further evaluation of in vivo Aβ imaging with PET. The fact that Aβ deposits can be detected by Aβ imaging in vivo is, in our opinion, a fact substantiated by a wealth of peer-reviewed data. 18F-Labeled Aβ imaging radiotracers may be approved for clinical use in the near future. If so, this will be the first PET radiopharmaceutical developed commercially and the first PET tracer approved for clinical use by the US Food and Drug Administration (FDA) since FDG. As such, it represents a landmark moment in the field of molecular imaging and should encourage further commercial investment and development in the field. The functionality, sensitivity, and specificity of Aβ plaque imaging agents has by now been demonstrated in a level of detail and reliability (including in vivo-to-postmortem autopsy correlations) that has not been required or provided for most other imaging tracers clinically used today. Many of the concerns raised by Moghbel and colleagues in their current editorial in the European Journal of Nuclear Medicine and Molecular Imaging have been resolved previously, and we attempted to summarize the available information on these issues, to allow a future rational discussion on common grounds of knowledge. As is the case for any clinical test, Aβ imaging does not represent a perfect tool and some justified concerns remain, such as the nonspecific white matter retention or the effects of atrophy and partial volume on quantification. However, none of these concerns reasonably question the general feasibility of Aβ imaging or have been demonstrated to hamper the value of this procedure for detection of fibrillar Aβ pathology. A discussion regarding clinical indications for Aβ imaging is as welcome and important as the debate about the causal role of Aβ pathology in the genesis of AD. However, both of these topics clearly need to be treated independently from the feasibility of Aβ imaging itself. Thus, we believe that the remaining issues do not justify a call to slow the clinical development of these radiotracers and to withhold the availability of this technology from those it could potentially help. In contrast, we believe that hindering the progress of this exciting new molecular imaging approach could send an erroneous and discouraging signal to groups interested in the development of other new diagnostic agents. The inability to obtain the information provided by Aβ imaging would most certainly slow down the urgently needed progress in understanding the basics of neurodegeneration and in the development of new approaches aiming to treat these devastating disorders. Aβ imaging has been repeatedly held up as one of the major successes of the past decade in the fight against AD. Thus, rather than to unnecessarily question the general feasibility of Aβ imaging, we believe we should vigorously foster the application of this unique new tool to improve our understanding of AD pathophysiology, to aid clinical diagnosis, and to advance the development of effective therapy.