PET Imaging Can Assist In Identifying Alzheimer's Disease Stage

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The findings suggest that interactions between beta-amyloid and tau lead to neurodegeneration in Alzheimer's.
The findings suggest that interactions between beta-amyloid and tau lead to neurodegeneration in Alzheimer's.

In a new study reported in JAMA Neurology, researchers at Washington University in St Louis, Missouri, and the University of Alabama, Birmingham, explored the potential of [18F]-AV-1451 positron emission tomography (PET) imaging to serve as a marker of disease staging in Alzheimer's disease (AD) and to elucidate interactions between β-amyloid and tauopathy.

Multiple imaging studies have found that the PET tracer [18F]-AV-1451 is one that binds to aggregated tau, and some findings have shown increased binding of this tracer in the neocortical areas of AD patients vs controls. In the current study, researchers investigated the utility of [18F]-AV-1451 PET imaging in 59 participants (64% male) with a mean age of 74 who had either AD dementia or were cognitively normal (CN).

Participants underwent [18F]-AV-1451 PET imaging and brain MRI, and a subset of the group was further assessed for cerebrospinal fluid levels of Aβ42 (CSF Aβ42), total tau, and ptau181. The authors compared binding in the hippocampus and previously defined AD cortical signature regions with hippocampal volume, AD signature cortical thickness, and CSF ptau181.

 

They also examined interactions between β-amyloid (Aβ), tau, and volume loss with the aim of further characterizing AD pathophysiology. They noted that according to emerging data, Aβ and age-related hippocampal tauopathy may not be sufficient to contribute to AD pathophysiology on their own; interaction between the 2 may be required for the development of the disease.

The results revealed the following observations:

  • AD participants could be distinguished from the CN group by the standardized uptake value ratio (SUVR) of [18F]-AV-1451 in the hippocampus and AD cortical signature regions (area under the receiver operating characteristic curve range [95% confidence interval, CI], 0.89 [0.73-1.00] to 0.98 [0.92-1.00]).
  • Cerebrospinal fluid Aβ42-positive (Aβ+) AD participants and cerebrospinal fluid Aβ42-negative (Aβ−) CN participants were best differentiated with an [18F]-AV-1451 SUVR cutoff value of 1.19 (sensitivity, 100%; specificity, 86%) from AD cortical signature regions, and the same cutoff value further differentiated Aβ+ CN participants into low vs high tau groups.
  • The presence of Aβ+ was linked with an increased [18F]-AV-1451 SUVR in AD cortical signature regions but not in the hippocampus, and no association was observed between the presence of Aβ+ alone and hippocampal volume or AD signature cortical thickness.
  • Volumetric loss in the hippocampus and AD cortical signature regions was associated with an increased [18F]-AV-1451 SUVR, and this relationship was “modified by Aβ status in the hippocampus but not in AD cortical signature regions,” the authors reported.
  • Aβ+ participants, but not Aβ- participants, showed an inverse association between hippocampal [18F]-AV-1451 SUVR and volume (R2 = 0.55; P < .001 and R2 = 0; P = .97, respectively).

The findings support the potential utility of [18F]-AV-1451 for staging preclinical AD and suggest that “interactions between Aβ and tau are the key for neurodegeneration due to AD,” the authors wrote. “In the hippocampus, Aβ likely transforms preexisting tauopathy to a more toxic species that results in neuronal injury,” and it may “intensify the spread of tauopathy, which in turn leads to neuronal loss that follows a topography that is similar to the observed spread of neurofibrillary tangles at autopsy,” they explained.  

Reference

Wang L, Benzinger TL, Su Y, et al. Evaluation of Tau Imaging in Staging Alzheimer Disease and Revealing Interactions Between β-Amyloid and Tauopathy. JAMA Neurol. 2016; doi:10.1001/jamaneurol.2016.2078

 

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