AstraZeneca presented the preclinical data on [18F]AZD4694 at the 9th International AD/PD meeting in Prague. In our preclinical studies, AZD4694 shows high affinity to amyloid plaque with very low non-specific interactions with white matter regions devoid of amyloid plaque. This low non-specific background provides a higher contrast and should support the potential to detect very low levels of amyloid. AZD4694 is currently in a Phase 1 study (in collaboration with Karolinska Institutet, Stockholm) with the objective to test clinical utility of this ligand. Our first data look very promising. We are supportive of ADNI, which has already made significant contributions to the field, and we have planned to make our ligand available for the sites in ADNI 2. The elegant study by Rosen et al., 2009, showing that PIB may be selective for pathological human-specific conformation of aggregated Aβ, indicates that we should be cautious when comparing results from different methods for evaluating Aβ plaque load in vitro (i.e., in vitro PET tracer...  Read more

AstraZeneca presented the preclinical data on [18F]AZD4694 at the 9th International AD/PD meeting in Prague. In our preclinical studies, AZD4694 shows high affinity to amyloid plaque with very low non-specific interactions with white matter regions devoid of amyloid plaque. This low non-specific background provides a higher contrast and should support the potential to detect very low levels of amyloid. AZD4694 is currently in a Phase 1 study (in collaboration with Karolinska Institutet, Stockholm) with the objective to test clinical utility of this ligand. Our first data look very promising. We are supportive of ADNI, which has already made significant contributions to the field, and we have planned to make our ligand available for the sites in ADNI 2. The elegant study by Rosen et al., 2009, showing that PIB may be selective for pathological human-specific conformation of aggregated Aβ, indicates that we should be cautious when comparing results from different methods for evaluating Aβ plaque load in vitro (i.e., in vitro PET tracer binding, ELISA for insoluble Aβ, and IHC). The data from Rosen et al. suggest that one should include PIB or another amyloid selective PET tracer when evaluating plaque load in vitro, to support translation to the in-vivo situation. Clearly more work is needed to unravel the molecular mechanism of amyloid ligand binding.

View all comments by Samuel Svensson

This paper is very interesting. Longitudinal data will be the key to proving an anatomic pattern of progression, and the data here suggest a leading candidate hypothesis. These results are consistent with some findings we reported last year (Becker et al., 2011) relating amyloid more strongly to posterior cingulate/precuneus thinning of cortex than to hippocampal volume loss. The confound that many (including myself) are hoping to probe for this issue is the contribution of tau deposition in the medial temporal lobe versus other cortices. Ligands for that are coming.

References:
Becker JA, Maye J, Gidicsin C, Rentz DR, Hedden T, Marshall G, Olson L, Buckner RL, Sperling RA, Johnson KA. FDG metabolism, amyloid deposition and APOE status in cognitively normal elderly subjects. Human Amyloid Imaging 2011 Meeting Abstracts. 2011 Jan 15. Abstract

View all comments by Keith Johnson