RT Journal Article
SR Electronic
T1 Differential contributions of Amyloid and Tau burden to Neurodegeneration in Alzheimer’s Disease: A multimodal in vivo PET study
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 124
OP 124
VO 57
IS supplement 2
A1 Gérard Bischof
A1 Jochen Hammes
A1 Thilo van Eimeren
A1 Alexander Drzezga
YR 2016
UL http://jnm.snmjournals.org/content/57/supplement_2/124.abstract
AB 124Objectives In Alzheimer’s Disease (AD), extracellular beta-amyloid plaques (Aβ) and intracellular neurofibrillary tangles (tau) represent the primary pathological hallmarks. However, the relative contributions of these protein aggregations to neurodegeneration remain elusive. Although modern molecular imaging methods allow to address this question in vivo, previous studies have failed to show a direct relationship between Aβ-deposition (as measured with [11C]PiB PET) and regional neurodegeneration (as measured with [18F]FDG-PET). With the advent of a novel PET tracer for tau imaging ([18F]AV-1451 aka T807) that shows high affinity to intracellular tangle pathology, it may now be possible to establish the missing link between protein aggregation pathology and neurodegeneration. A better understanding of the relative contribution of tau and Aβ pathology to neurodegeneration in AD will advance our knowledge of disease mechanisms and provide crucial information for disease-modifying interventions. Here, we assessed the relationship of tau and Aβ pathology to regional and global measures of hypometabolism in AD patients using multimodal PET.Methods We examined glucose hypometabolism (assessed by [18F]FDG PET), measures of Tau ([18F]AV-1451 PET), and Aβ ([11C]PiB PET) in ten AD patients. After spatial normalization, we created standardized uptake value ratio (SUVR) images normalized by the non-specific binding potential of the cerebellum. We created mean and standard deviation images of glucose metabolism and tau deposition using modality-specific reference samples of age-matched healthy controls. We then calculated z-score deviation maps to examine disease-related patterns of hypometabolism and tau deposition. A structure-based parcellation of cortical and hippocampal brain regions using the automatic anatomic labeling atlas (AAL) was applied to the deviation images. Z-scores and SUVR values from the [11C]PiB images for each individual were extracted. We performed correlational and multivariate analyses to investigate the relationship of tau deposition and amyloid burden to hypometabolism.Results Across brain regions, we found a strong linear relationship between tau deposition and hypometabolism (r=.71, p<.001), whereas measures of Aβ were not related to hypometabolism (r=-.17, ns). Within regions, association of tau deposition and hypometabolism was most pronounced in the parietal, temporal and occipital lobe. Interestingly, in the very same regions, we also found an association of hypometabolism and Aβ measures. Multivariate analysis revealed that frontal and temporal hypometabolism was predicted only by tau deposition, whereas for occipital brain regions, we found interactive effects of tau and amyloid best predicting hypometabolism.Conclusions Measuring tau deposition using [18F]AV-1451 PET in conjunction with [18F]FDG PET and [11C]PiB PET offers novel insights into the neurodegenerative characteristics in AD. Our results provide evidence for the hypothesis that tau pathology may represent a direct instigator of neuronal injury and, thus, of regional neurodegeneration in AD. In contrast, effects of Aβ deposition on neuronal function (if present) were observed only in dependence of tau pathology. This implicates a more indirect role of Aβ aggregation in causing neurodegeneration. This study emphasizes that tau pathology may prove to be an instrumental target for disease-modifying strategies in AD.