Jasmeer P Chhatwal1, Aaron P Schultz1, Gad A Marshall1, Brendon Boot1, Teresa Gomez-Isla1, Julien Dumurgier1, Molly LaPoint1, Clemens Scherzer1, Allyson D Roe1, Bradley T Hyman1, Reisa A Sperling1, Keith A Johnson2. 1. From Harvard Medical School (J.P.C., A.P.S., G.A.M., B.B., T.G.-I., C.S., B.T.H., R.A.S., K.A.J.); Massachusetts General Hospital (J.P.C., A.P.S., G.A.M., B.B., T.G.-I., J.D., M.L., A.D.R., B.T.H., R.A.S., K.A.J.), Boston; Martinos Center for Biomedical Imaging (J.P.C., A.P.S., M.L., R.A.S., K.A.J.), Charlestown; Brigham and Women's Hospital (G.A.M., B.B., C.S., R.A.S., K.A.J.), Boston; Biogen (B.B.), Cambridge, MA; Lariboisiere Hospital Memory Center (J.D.), APHP, University Paris 7 Denis Diderot, France; and Harvard NeuroDiscovery Center (C.S.), Boston, MA. 2. From Harvard Medical School (J.P.C., A.P.S., G.A.M., B.B., T.G.-I., C.S., B.T.H., R.A.S., K.A.J.); Massachusetts General Hospital (J.P.C., A.P.S., G.A.M., B.B., T.G.-I., J.D., M.L., A.D.R., B.T.H., R.A.S., K.A.J.), Boston; Martinos Center for Biomedical Imaging (J.P.C., A.P.S., M.L., R.A.S., K.A.J.), Charlestown; Brigham and Women's Hospital (G.A.M., B.B., C.S., R.A.S., K.A.J.), Boston; Biogen (B.B.), Cambridge, MA; Lariboisiere Hospital Memory Center (J.D.), APHP, University Paris 7 Denis Diderot, France; and Harvard NeuroDiscovery Center (C.S.), Boston, MA. kajohnson@pet.mgh.harvard.edu.
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 β-amyloid 1-42 (Aβ42). METHODS: T-tau, p-tau, and Aβ42 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 = 0.48; p < 0.01) and at trend level with t-tau (partial r = 0.30; p = 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 = 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.
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 β-amyloid 1-42 (Aβ42). METHODS: T-tau, p-tau, and Aβ42 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 = 0.48; p < 0.01) and at trend level with t-tau (partial r = 0.30; p = 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 = 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.
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