Tau and Aβ imaging, CSF measures, and cognition in Alzheimer’s disease
Science Translational Medicine
11 May 2016
Vol 8, Issue 338
p. 338ra66
A window into Alzheimer’s disease
Alzheimer’s disease is pathologically defined by the accumulation of β-amyloid (Aβ) plaques and tau tangles. The cognitive and pathological correlates of Aβ deposition have been well studied owing to the availability of PET imaging ligands. Using newly available tau imaging agents, Brier et al. now explore relationships among tau pathology and Aβ with PET imaging, cerebrospinal fluid measures of disease, and cognition. Overall, tau imaging provided a more robust predictor of disease status than did Aβ imaging. Thus, whereas Aβ imaging provides a good marker for early disease state, tau imaging is a more robust predictor of disease progression.
Abstract
Alzheimer’s disease (AD) is characterized by two molecular pathologies: cerebral β-amyloidosis in the form of β-amyloid (Aβ) plaques and tauopathy in the form of neurofibrillary tangles, neuritic plaques, and neuropil threads. Until recently, only Aβ could be studied in humans using positron emission tomography (PET) imaging owing to a lack of tau PET imaging agents. Clinical pathological studies have linked tau pathology closely to the onset and progression of cognitive symptoms in patients with AD. We report PET imaging of tau and Aβ in a cohort of cognitively normal older adults and those with mild AD. Multivariate analyses identified unique disease-related stereotypical spatial patterns (topographies) for deposition of tau and Aβ. These PET imaging tau and Aβ topographies were spatially distinct but correlated with disease progression. Cerebrospinal fluid measures of tau, often used to stage preclinical AD, correlated with tau deposition in the temporal lobe. Tau deposition in the temporal lobe more closely tracked dementia status and was a better predictor of cognitive performance than Aβ deposition in any region of the brain. These data support models of AD where tau pathology closely tracks changes in brain function that are responsible for the onset of early symptoms in AD.
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Supplementary Material
Summary
Methods
Fig. S1. PET tau and Aβ SUVR images from representative subjects in both the CDR0 and CDR>0 group.
Table S1. Analysis of variance (ANOVA) results related to SVD topographies.
Table S2. Mean PET and CSF correlation matrix.
Table S3. Regional regression β values.
Table S4. Comparison of PET tau SVD results.
Table S5. Leave-one-out analysis results.
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Published In
Science Translational Medicine
Volume 8 | Issue 338
May 2016
May 2016
Copyright
Copyright © 2016, American Association for the Advancement of Science.
Submission history
Received: 12 January 2016
Accepted: 22 April 2016
Acknowledgments
This study was funded by NIH grants P50AG05681, P01AG003991, P01AG026276, 5P30NS048056, 2UL1TR000448, and 5RO1AG04343404 and NSF grant DMS1300280. Funding was also provided by Charles F. and Joanne Knight Alzheimer’s Research Initiative, Hope Center for Neurological Disorders, and a generous support from Fred Simmons and Olga Mohan Fund and Paula and Rodger Riney Fund. Avid Radiopharmaceuticals (a wholly owned subsidiary of Eli Lilly) provided florbetapir doses and partial financial support for the florbetapir scanning sessions. Avid Radiopharmaceuticals also provided the precursor for T807 and radiopharmaceutical chemistry and technology for the Washington University Investigational New Drug, under which this study was performed. Author contributions: M.R.B. developed the methodology, performed formal analysis, and wrote the paper; B.G. performed formal analysis; K.F. curated the data and developed the methodology; J.M. and A.S. developed the methodology and computation; J.C. performed formal analysis and curated the data; P.A. performed project administration and was responsible for subject accrual; Y.S. developed the methodology; J.H. contributed resources; N.J.C., D.M.H., A.M.F., and J.C.M. contributed to study conception, resources, and project administration; and B.M.A. and T.L.S.B. provided supervision and conception of the study. The staff of the Imaging Core at the Knight Alzheimer’s Disease Research Center performed imaging acquisition. All authors critically revised the manuscript. Competing interests: D.M.H. is co-founder of and on the scientific advisory board for C2N Diagnostics and consults for Genentech, Eli Lilly, AbbVie, Denali, and NeuroPhage. A.M.F. is on the scientific advisory board for IBL International and Roche and is a consultant for DiamiR. J.M. consults for Lilly and Takeda. B.G. is participating in a clinical trial with Avid Radiopharmaceuticals. Data and materials availability: These data are available by request at the Knight Alzheimer’s Disease Research Center at Washington University in St. Louis. AV-1451 was produced under a material transfer agreement between Washington University and Avid Radiopharmaceuticals.
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