Regional profiles of the candidate tau PET ligand 18F-AV-1451 recapitulate key features of Braak histopathological stages.
Adam J. Schwarz,Peng Yu,Bradley B. Miller,Sergey Shcherbinin,James Dickson,Michael Navitsky,Abhinay D. Joshi,Michael D. Devous,Mark S. Mintun +8 more
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The estimated Braak stage was significantly associated with amyloid status, diagnostic category and measures of global cognition and could be classified into patterns similar to those prescribed by Braak neuropathological staging of tau pathology.Abstract:
SEE THAL AND VANDENBERGHE DOI101093/BRAIN/AWW057 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Post-mortem Braak staging of neurofibrillary tau tangle topographical distribution is one of the core neuropathological criteria for the diagnosis of Alzheimer's disease. The recent development of positron emission tomography tracers targeting neurofibrillary tangles has enabled the distribution of tau pathology to be imaged in living subjects. Methods for extraction of classic Braak staging from in vivo imaging of neurofibrillary tau tangles have not yet been explored. Standardized uptake value ratio images were calculated from 80-100 minute (18)F-AV-1451 (also known as T807) positron emission tomography scans obtained from n = 14 young reference subjects (age 21-39 years, Mini-Mental State Examination 29-30) and n = 173 older test subjects (age 50-95 years) comprising amyloid negative cognitively normal (n = 42), clinically-diagnosed mild cognitive impairment (amyloid positive, n = 47, and amyloid negative, n = 40) and Alzheimer's disease (amyloid positive, n = 28, and amyloid negative, n = 16). We defined seven regions of interest in anterior temporal lobe and occipital lobe sections corresponding closely to those used as decision points in Braak staging. An algorithm based on the Braak histological staging procedure was applied to estimate Braak stages directly from the region of interest profiles in each subject. Quantitative region-based analysis of (18)F-AV-1451 images yielded region of interest and voxel level profiles that mirrored key features of neuropathological tau progression including profiles consistent with Braak stages 0 through VI. A simple set of decision rules enabled plausible Braak stages corresponding to stereotypical progression patterns to be objectively estimated in 149 (86%) of test subjects. An additional 12 (7%) subjects presented with predefined variant profiles (relative sparing of the hippocampus and/or occipital lobe). The estimated Braak stage was significantly associated with amyloid status, diagnostic category and measures of global cognition. In vivo (18)F-AV-1451 positron emission tomography images across the Alzheimer's disease spectrum could be classified into patterns similar to those prescribed by Braak neuropathological staging of tau pathology.read more
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NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease
Clifford R. Jack,David A. Bennett,Kaj Blennow,Maria C. Carrillo,Billy Dunn,Samantha Budd Haeberlein,David M. Holtzman,William J. Jagust,Frank Jessen,Jason Karlawish,Enchi Liu,José Luis Molinuevo,Thomas J. Montine,Creighton H. Phelps,Katherine P. Rankin,Christopher C. Rowe,Philip Scheltens,Eric Siemers,Heather M. Snyder,Reisa A. Sperling,Cerise L Elliott,Eliezer Masliah,Laurie M. Ryan,Nina Silverberg +23 more
TL;DR: This research framework seeks to create a common language with which investigators can generate and test hypotheses about the interactions among different pathologic processes (denoted by biomarkers) and cognitive symptoms and envision that defining AD as a biological construct will enable a more accurate characterization and understanding of the sequence of events that lead to cognitive impairment that is associated with AD.
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Reconsideration of Amyloid Hypothesis and Tau Hypothesis in Alzheimer's Disease
Fuyuki Kametani,Masato Hasegawa +1 more
TL;DR: Recent findings indicate that the main factor underlying the development and progression of AD is tau, not Aβ, and the deficiencies of the amyloid hypothesis are described.
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TL;DR: The goal was to develop cut points for amyloid positron emission tomography (PET), tau PET, flouro‐deoxyglucose (FDG) PET, and MRI cortical thickness.
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Amyloid-β plaques enhance Alzheimer's brain tau-seeded pathologies by facilitating neuritic plaque tau aggregation.
Zhuohao He,Jing L. Guo,Jennifer D. McBride,Sneha Narasimhan,Hyesung Kim,Lakshmi Changolkar,Bin Zhang,Ronald J. Gathagan,Cuiyong Yue,Christopher G. Dengler,Anna Stieber,Magdalena Nitla,Douglas A. Coulter,Douglas A. Coulter,Ted Abel,Kurt R. Brunden,John Q. Trojanowski,Virginia M.-Y. Lee +17 more
TL;DR: It is found that Aβ plaques created a unique environment that facilitated the rapid amplification of proteopathic AD-tau seeds into large tau aggregates, initially appearing as NP tau, which was followed by the formation and spread of NFTs and NTs, likely through secondary seeding events.
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Antoine Leuzy,Konstantinos Chiotis,Konstantinos Chiotis,Laetitia Lemoine,Per-Göran Gillberg,Ove Almkvist,Ove Almkvist,Elena Rodriguez-Vieitez,Agneta Nordberg,Agneta Nordberg +9 more
TL;DR: Findings from in vitro and in vivo studies using both initial and new tau ligands are described and discussed, including their relation to biomarkers for amyloid-β and neurodegeneration, and cognitive findings.
References
More filters
Journal ArticleDOI
The diagnosis of dementia due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer's disease
Guy M. McKhann,Guy M. McKhann,David S. Knopman,Howard Chertkow,Bradley T. Hyman,Clifford R. Jack,Claudia H. Kawas,William E. Klunk,Walter J. Koroshetz,Jennifer J. Manly,Richard Mayeux,Richard C. Mohs,John C. Morris,Martin N. Rossor,Philip Scheltens,Maria C. Carrillo,Bill Thies,Sandra Weintraub,Creighton H. Phelps +18 more
TL;DR: The workgroup sought to ensure that the revised criteria would be flexible enough to be used by both general healthcare providers without access to neuropsychological testing, advanced imaging, and cerebrospinal fluid measures, and specialized investigators involved in research or in clinical trial studies who would have these tools available.
Journal ArticleDOI
Neuropathological stageing of Alzheimer-related changes.
Heiko Braak,Eva Braak +1 more
TL;DR: The investigation showed that recognition of the six stages required qualitative evaluation of only a few key preparations, permitting the differentiation of six stages.
Journal Article
The diagnosis of mild cognitive impairment due to Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease
Guy M. McKhann,David S. Knopman,Howard Chertkow,Bradley T. Hyman,C. R. Jack,Claudia H. Kawas,William E. Klunk,Walter J. Koroshetz,Jennifer J. Manly,Richard Mayeux,Richard C. Mohs,John C. Morris,Martin N. Rossor,Philip Scheltens,Maria C. Carrillo,Bill Thies,Sandra Weintraub,Creighton H. Phelps +17 more
Journal ArticleDOI
Tracking pathophysiological processes in Alzheimer's disease: an updated hypothetical model of dynamic biomarkers.
Clifford R. Jack,David S. Knopman,William J. Jagust,Ronald C. Petersen,Michael W. Weiner,Paul S. Aisen,Leslie M. Shaw,Prashanthi Vemuri,Heather J. Wiste,Stephen D. Weigand,Timothy G. Lesnick,Vernon S. Pankratz,Michael C. Donohue,John Q. Trojanowski +13 more
TL;DR: In this article, a model of the major biomarkers of Alzheimer's disease (AD) was proposed and the authors described the temporal evolution of AD biomarkers in relation to each other and to the onset and progression of clinical symptoms.
Journal ArticleDOI
Phases of Aβ-deposition in the human brain and its relevance for the development of AD
TL;DR: Aβ-deposition in the entire brain follows a distinct sequence in which the regions are hierarchically involved and expands anterogradely into regions that receive neuronal projections from regions already exhibiting Aβ.
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