[18F]-AV1451 Autoradiography Signal Correlates with Anti-pathological Tau IHC Signal in AD Post-Mortem Cortical Tissue Sections

Objectives Background: Previous studies have shown that [18F]-AV1451 is a specific PET imaging tracer to detect pathological tau in Alzheimer’s disease (AD). This study has a direct comparison of the localization of [18F]-AV-1451 with the localization of AT8 anti-tau antibody in AD patient post-mortem cortical brain tissue sections having a wide range of pathological tau accumulation. Objective: To determine if the autoradiography (ARG) signal from [18F]-AV1451 matches closely with the distribution and signal intensity of the Tau-antibody AT8 IHC in the same brain section of AD patients and normal controls.

Methods Methods: [18F]-AV1451 (20 µCi) was added to fresh frozen brain sections (10 µm) from 30 AD and 10 age-matched controls to obtain autoradiography (ARG) images. The location and radioactivity levels of bound 18F tracer in the brain section were recorded by a Fuji Film Bio-Imaging System FLA-7000. The same tissue sections were stained with the phospho-Tau antibody AT-8 and labeled with a fluorescent dye. The IF preparations were imaged using a NanoZoomer 2.0HT (Hamamatsu), which allows for both a macroscopic and microscopic view of the immunofluorescence signal. Further analysis of section areas and signal intensity were performed using Photoshop and Image J software.

Results Results: The [18F]-AV1451 ARG signal is well matched to anti-tau IHC signal in the same AD brain section (Figure 1). There is a good correlation (r = 0.842, P < 0.0001) between the area of AT8 IHC signal and that of the [18F]AV-1451 ARG signal in AD brain sections (Figure 2). In addition, the intensity of the ARG signal matched the amount of pathological tau in the gray matter region of sections from 30 AD and 3 normal brains as shown by IF with cross-subject correlation of 0.68 (Figure 3).

Conclusions Conclusion: [18F]-AV1451 ARG signal correlates well with the distribution of pathological tau when immunostaining with AT-8 tau antibody is performed on the same section as ARG. These results further support [18F]-AV1451 as a PET imaging tracer for pathological tau aggregation in AD.