It was with great interest that we read this paper, as it was the first paper to quantitatively compare measures of Aß burden, atrophy, and hypometabolism in Alzheimer's disease (AD) patients using a voxel-based method. The authors' finding that "Aß deposition did not correlate to either atrophy or hypometabolism" substantiates the widely reported differences between these measures in the literature. It was the same obse...
It was with great interest that we read this paper, as it was the first paper to quantitatively compare measures of Aß burden, atrophy, and hypometabolism in Alzheimer's disease (AD) patients using a voxel-based method. The authors' finding that "Aß deposition did not correlate to either atrophy or hypometabolism" substantiates the widely reported differences between these measures in the literature. It was the same observation of inconsistencies in regional distribution patterns--namely, unexpectedly high uptake of amyloid-PET radiotracers in the frontal cortex and white matter, along with surprisingly low uptake in temporoparietal regions-- that led us to publish an editorial on the subject in February of 2012 (Moghbel et al., 2012).
This discrepancy between Aß burden, as measured by amyloid-PET, and other assessments of neurodegeneration has been met by a number of hypotheses. It has been suggested that Aß may be responsible for neurodegeneration in preclinical stages of AD, but not in symptomatic stages. If this were true, the patterns of atrophy and hypometabolism would be expected to align with those of Aß deposition, albeit with a temporal delay. However, even in the medial temporal lobe, where neurodegeneration is most pronounced at the earliest stages of the disease, a "predominance of atrophy and hypometabolism" is observed alongside "low Aß burden." An alternate hypothesis proposes that Aß causes neurodegeneration at a distance rather than locally in humans. But as the authors themselves note, this lies in contrast to what has been documented in animal models, which reveal "severe neurite abnormalities...in the vicinity of Aß deposits."
Other explanations that could account for the poor correlation between Aß and other neurodegerative measures include the apparent non- specificity of amyloid-PET probes such as [18F]florbetapir, as well as the possibly limited role of Aß in causing neuronal damage at any stage of AD. The former account would necessitate more specific assays of Aß deposition, while the latter would challenge the validity of Aß as a surrogate marker. The limited correlation that has been demonstrated between Aß burden and the clinical endpoint of neurodegeneration suggests to us that assessments of Aß deposition, most notably through amyloid-PET imaging, may not be appropriate for diagnostic purposes. La Joie et al.'s findings therefore lead us to believe that other avenues to the diagnosis of AD may prove more clinically valuable.
Reference
Moghbel MC, Saboury B, Basu S, Metzler SD, Torigian DA, Langstrom B, Alavi A (2012) Amyloid-ß imaging with PET in Alzheimer's disease: is it feasible with current radiotracers and technologies? (2012) Eur J Nucl Med Mol Imaging 39(2):202-8.
None declared