TY - JOUR
T1 - Associations between [18F]AV1451 tau PET and CSF measures of tau pathology in a clinical sample
AU - La Joie, Renaud
AU - Bejanin, Alexandre
AU - Fagan, Anne M.
AU - Ayakta, Nagehan
AU - Baker, Suzanne L.
AU - Bourakova, Viktoriya
AU - Boxer, Adam L.
AU - Cha, Jungho
AU - Karydas, Anna
AU - Jerome, Gina
AU - Maass, Anne
AU - Mensing, Ashley
AU - Miller, Zachary A.
AU - O'Neil, James P.
AU - Pham, Julie
AU - Rosen, Howard J.
AU - Tsai, Richard
AU - Visani, Adrienne V.
AU - Miller, Bruce L.
AU - Jagust, William J.
AU - Rabinovici, Gil D.
N1 - Funding Information:
R. La Joie and A. Bejanin report no disclosures relevant to the manuscript. A. Fagan is supported by NIH grants including P50AG005681, P01AG003991, P01AG026276, and UF01AG03243807. Dr. Fagan is on the Scientific Advisory Boards for Roche Diagnostics, IBL International, and AbbVie and consults for Biogen, DiamiR LLC, LabCorp, and Araclon Biotech/Griffols. N. Ayakta, S. Baker, and V. Bourakova report no disclosures relevant to the manuscript. A. Boxer receives research support from Avid, Biogen, Bristol Myers Squibb, C2N Diagnostics, Cortice Biosciences, Eli Lilly, Forum Pharmaceuticals, Genentech, and TauRx. He has served as a consultant for Asceneuron, Ipierian, Isis, Janssen, and Merck. He has stock/options in Alector and Delos. J. Cha, A. Karydas, G. Jerome, A. Maass, and A. Mensing report no disclosures relevant to the manuscript. Z. Miller is funded by an NIH grant (K23 AG048291). J. O’Neil receives research support from Genzyme Corp, the US Department of Energy, the US Army Medical Research & Materiel Command, and the NIH. J. Pham reports no disclosures relevant to the manuscript. H. Rosen receives research support from NIH/ National Institute on Aging, RO1 AG032306 (PI), PO1 AG019724 (Core leader), AG045333 (PI), and AG023501 (core leader). R. Tsai receives research support from the University of California. He also consulted for ExpertConnect and Grifols. A. Visani reports no disclosures relevant to the manuscript. B. Miller receives grant support from the NIH/ NIA and the Centers for Medicare & Medicaid Services as grants for the Memory and Aging Center. As an additional disclosure, Dr. Miller serves as Medical Director for the John Douglas French Foundation; Scientific Director for the Tau Consortium; Director/Medical Advisory Board of the Larry L. Hillblom Foundation; Scientific Advisory Board Member for the National Institute for Health Research Cambridge Biomedical Research Centre and its subunit, the Biomedical Research Unit in Dementia (UK); and Board Member for the American Brain Foundation (ABF). W. Jagust has served as a consultant to BioClinica, Genentech, and Novartis Pharmaceuticals. G. Rabinovici receives research support from Avid Radiopharmaceuticals, GE Healthcare, and Piramal, and has received consulting fees or speaking honoraria from Roche, Eisai, Lundbeck, Piramal, Genentech, Merck, and Putnam. Go to Neurology.org/N for full disclosures.
Funding Information:
Supported by the Alzheimer's Association (AARF-16-443577 to R.L.J.), Tau Consortium (to G.D.R. and W.J.J.), National Institute on Aging grants (R01-AG045611 to G.D.R., R01-AG034570 to W.J.J., P50-AG023501 to B.L.M. and G.D.R., P01-AG19724 to W.J.J. and B.L.M., 4TNIR01-AG038791 to A.L.B., G.D.R., and W.J.J., ARTFL U54-NS092089 to A.L.B., B.L.M., G.D.R., and H.J.R.), State of California Department of Health Services Alzheimer's Disease Research Centre of California grant (04-33516 to B.L.M.), and Michael J. Fox Foundation (to G.D.R. and W.J.J.). Avid Radiopharmaceuticals enabled use of the [18F]AV1451 tracer by providing precursor, but did not provide direct funding and was not involved in data analysis or interpretation.
Funding Information:
This study was funded by the Alzheimer’s Association, the Tau Consortium, several National Institute on Aging grants, the State of California Department of Health Services Alzheimer’s Disease Research Center of California grant, and the Michael J. Fox foundation. Go to Neurology.org/N for full disclosures.
Funding Information:
Supported by the Alzheimer’s Association (AARF-16-443577 to R.L.J.), Tau Consortium (to G.D.R. and W.J.J.), National Institute on Aging grants (R01-AG045611 to G.D.R., R01-AG034570 to W.J.J., P50-AG023501 to B.L.M. and G.D.R., P01-AG19724 to W.J.J. and B.L.M., 4TNIR01-AG038791 to A.L.B., G.D.R., and W.J.J., ARTFL U54-NS092089 to A.L.B., B.L.M., G.D.R., and H.J.R.), State of California Department of Health Services Alzheimer’s Disease Research Centre of California grant (04–33516 to B.L.M.), and Michael J. Fox Foundation (to G.D.R. and W.J.J.). Avid Radiopharmaceuticals enabled use of the [18F]AV1451 tracer by providing precursor, but did not provide direct funding and was not involved in data analysis or interpretation.
Publisher Copyright:
© 2018 American Academy of Neurology
PY - 2018/1/23
Y1 - 2018/1/23
N2 - Objective To assess the relationships between fluid and imaging biomarkers of tau pathology and compare their diagnostic utility in a clinically heterogeneous sample. Methods Fifty-three patients (28 with clinical Alzheimer disease [AD] and 25 with non-AD clinical neurodegenerative diagnoses) underwent β-amyloid (Aβ) and tau ([18F]AV1451) PET and lumbar puncture. CSF biomarkers (Aβ42, total tau [t-tau], and phosphorylated tau [p-tau]) were measured by multianalyte immunoassay (AlzBio3). Receiver operator characteristic analyses were performed to compare discrimination of Aβ-positive AD from non-AD conditions across biomarkers. Correlations between CSF biomarkers and PET standardized uptake value ratios (SUVR) were assessed using skipped Pearson correlation coefficients. Voxelwise analyses were run to assess regional CSF-PET associations. Results [18F]AV1451-PET cortical SUVR and p-tau showed excellent discrimination between Aβ-positive AD and non-AD conditions (area under the curve 0.92-0.94; ≤0.83 for other CSF measures), and reached 83% classification agreement. In the full sample, cortical [18F]AV1451 was associated with all CSF biomarkers, most strongly with p-tau (r = 0.75 vs 0.57 for t-tau and −0.49 for Aβ42). When restricted to Aβ-positive patients with AD, [18F]AV1451 SUVR correlated modestly with p-tau and t-tau (both r = 0.46) but not Aβ42 (r = 0.02). On voxelwise analysis, [18F]AV1451 correlated with CSF p-tau in temporoparietal cortices and with t-tau in medial prefrontal regions. Within AD, Mini-Mental State Examination scores were associated with [18F]AV1451-PET, but not CSF biomarkers. Conclusion [18F]AV1451-PET and CSF p-tau had comparable value for differential diagnosis. Correlations were robust in a heterogeneous clinical group but attenuated (although significant) in AD, suggesting that fluid and imaging biomarkers capture different aspects of tau pathology. Classification of evidence This study provides Class III evidence that, in a clinical sample of patients with a variety of suspected neurodegenerative diseases, both CSF p-tau and [18F]AV1451 distinguish AD from non-AD conditions.
AB - Objective To assess the relationships between fluid and imaging biomarkers of tau pathology and compare their diagnostic utility in a clinically heterogeneous sample. Methods Fifty-three patients (28 with clinical Alzheimer disease [AD] and 25 with non-AD clinical neurodegenerative diagnoses) underwent β-amyloid (Aβ) and tau ([18F]AV1451) PET and lumbar puncture. CSF biomarkers (Aβ42, total tau [t-tau], and phosphorylated tau [p-tau]) were measured by multianalyte immunoassay (AlzBio3). Receiver operator characteristic analyses were performed to compare discrimination of Aβ-positive AD from non-AD conditions across biomarkers. Correlations between CSF biomarkers and PET standardized uptake value ratios (SUVR) were assessed using skipped Pearson correlation coefficients. Voxelwise analyses were run to assess regional CSF-PET associations. Results [18F]AV1451-PET cortical SUVR and p-tau showed excellent discrimination between Aβ-positive AD and non-AD conditions (area under the curve 0.92-0.94; ≤0.83 for other CSF measures), and reached 83% classification agreement. In the full sample, cortical [18F]AV1451 was associated with all CSF biomarkers, most strongly with p-tau (r = 0.75 vs 0.57 for t-tau and −0.49 for Aβ42). When restricted to Aβ-positive patients with AD, [18F]AV1451 SUVR correlated modestly with p-tau and t-tau (both r = 0.46) but not Aβ42 (r = 0.02). On voxelwise analysis, [18F]AV1451 correlated with CSF p-tau in temporoparietal cortices and with t-tau in medial prefrontal regions. Within AD, Mini-Mental State Examination scores were associated with [18F]AV1451-PET, but not CSF biomarkers. Conclusion [18F]AV1451-PET and CSF p-tau had comparable value for differential diagnosis. Correlations were robust in a heterogeneous clinical group but attenuated (although significant) in AD, suggesting that fluid and imaging biomarkers capture different aspects of tau pathology. Classification of evidence This study provides Class III evidence that, in a clinical sample of patients with a variety of suspected neurodegenerative diseases, both CSF p-tau and [18F]AV1451 distinguish AD from non-AD conditions.
UR - http://www.scopus.com/inward/record.url?scp=85051184828&partnerID=8YFLogxK
U2 - 10.1212/WNL.0000000000004860
DO - 10.1212/WNL.0000000000004860
M3 - Article
C2 - 29282337
AN - SCOPUS:85051184828
VL - 90
SP - E282-E290
JO - Neurology
JF - Neurology
SN - 0028-3878
IS - 4
ER -