[P2–383]: COMPARISON OF REGIONAL FLORTAUCIPIR PET TO QUANTITATIVE TAU AND AMYLOID IMMUNOASSAY IN PATIENTS WITH ALZHEIMER's DISEASE PATHOLOGY: A PILOT CLINICO‐PATHOLOGICAL STUDY

Abstract

PET tracers for tau pathology in Alzheimer's disease (AD) are of increasing interest as diagnostics and as markers of disease severity. The objective of this study was to make a quantitative comparison of 18F flortaucipir (F18-AV-1451) PET uptake across a range of brain regions and density of tau and amyloid pathology observed at autopsy. Patients at end-of-life were recruited for this pilot phase of a pivotal clinical trial. Participants had an injection of ∼370 mBq 18F flortaucipir followed by PET imaging from 80–100 minutes after injection. After death, blocks of tissue from neocortical and limbic regions were obtained. Subject-specific PET regions of interest corresponding to pathology blocks were constructed for 14 regions in each hemisphere. Regions were hand drawn on the PET images using photographs of the gross pathology blocks as reference. SUVr values were calculated using a cerebellar reference region. Tau and amyloid pathology was assessed with a quantitative antibody capture assay (Histelide) using the AT8 and a abeta 1–42 specific antibody, respectively. Three participants with a clinical diagnosis of Alzheimer's disease were included. The intervals between imaging and death for the three cases were 4, 12 and 27 days. Braak staging by hemisphere ranged from IV to VI. Examination of individual tissue blocks showed that tau pathology ranged from absent in some blocks to frequent others. Regional flortaucipir SUVr values ranged from 1.02 to 2.60. There was a highly significant correlation for all patients between regional SUVr and quantitative tau immunoassay (pearson r = 0.82; p<0.0001). There was a significant correlation between density of amyloid and tau pathology as measured by immunoassay across regions (pearson r = 0.69; p<0.0001). As a result, there was an apparent correlation between flortaucipir SUVr and amyloid pathology that did not persist after adjustment for tau pathology. The results of this pilot study support a quantitative relationship between flortaucipir SUVr values and quantitative measures of tau pathology at autopsy. In addition, we found a correlation between density of tau and amyloid pathology across different brain regions. Additional research, including more cases, is needed to confirm the generalizability of these results.