Temporal T807 binding correlates with CSF tau and phospho-tau in normal elderly

Abstract

Objective: To better understand cross-sectional relationships between CSF and PET measures of tau pathology, we compared regional and global measures of 18 F-T807 (AV-1451) PET to CSF protein levels of total tau (t-tau), phosphorylated tau (p-tau), and b-amyloid 1-42 (Ab42).Methods: T-tau, p-tau, and Ab42 levels were assessed using INNOTEST xMAP immunoassays.Linear regression was used to compare regional and global measures of 18 F-T807 standardized uptake value ratios (SUVR) to CSF protein levels using data from 31 cognitively unimpaired elderly participants in the Harvard Aging Brain study.Results: After controlling for sex and age, total cortical 18 F-T807 binding was significantly correlated with p-tau (partial r 5 0.48; p , 0.01) and at trend level with t-tau (partial r 5 0.30; p 5 0.12). Regional 18 F-T807 measures were more strongly correlated with CSF protein levels than the global measure, with both t-tau and p-tau significantly correlated with 18 F-T807 SUVR in entorhinal, parahippocampal, and inferior temporal cortical regions (partial r 5 0.53-0.73). Peak correlations between CSF and PET measures of tau were similar to those between CSF and PET measures of amyloid burden. Finally, we observed significantly higher temporal T807 SUVR in individuals with high amyloid burden.Conclusions: These data support the link between 18 F-T807 PET and CSF measures of tau pathology. In these cognitively normal individuals with 18 F-T807 binding largely restricted to the temporal lobe, 18 F-T807 SUVR in temporal regions appeared more reflective of CSF t-tau and p-tau than a total cortical measure. Neurology ® 2016;87:920-926 GLOSSARY Ab 5 b-amyloid; Ab42 5 b-amyloid 1-42; AD 5 Alzheimer disease; ADNI 5 Alzheimer's Disease Neuroimaging Initiative; CNE 5 cognitively normal elderly; DVR 5 distribution volume ratio; FLR 5 frontal, parietal, retrosplenial, and lateral temporal cortical regions; HAB 5 Harvard Aging Brain; ITC 5 inferior temporal neocortex; MCI 5 mild cognitive impairment; MGH 5 Massachusetts General Hospital; MMSE 5 Mini-Mental State Examination; MTC 5 middle temporal neocortex; NFT 5 neurofibrillary tangle; p-tau 5 phosphorylated tau; PiB 5 Pittsburgh compound B; ROI 5 region of interest; SUVR 5 standardized uptake value ratio; t-tau 5 total tau.Accumulations of b-amyloid (Ab) and intracellular tau are defining characteristics of Alzheimer disease (AD) pathology. CSF assays of Ab 1-42 (Ab42), total tau (t-tau), and tau phosphorylated at residue 181 (p-tau) proteins are commonly used tools for identifying individuals harboring AD pathology. These CSF-based assays are increasingly being supplemented with imaging biomarkers reflecting molecular pathology in vivo. Following the initial description of 11 C Pittsburgh compound B (PiB), 1 PET-based measures of amyloid pathology have come into increasing use in research and clinical settings. Several groups have demonstrated that PET measures of amyloid burden correlate well with CSF Ab42 measurements, and can be used in concert with other biomarkers as p...

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