Journal ArticleDOI
[18F]T807, a novel tau positron emission tomography imaging agent for Alzheimer's disease
Chunfang Xia,Janna Arteaga,Gang Chen,Umesh B. Gangadharmath,Luis F. Gomez,Dhanalakshmi Kasi,Chung Lam,Qianwa Liang,Changhui Liu,Vani P. Mocharla,Fanrong Mu,Anjana Sinha,Helen Su,A. Katrin Szardenings,Joseph C. Walsh,Eric Wang,Chul Yu,Wei Zhang,Tieming Zhao,Hartmuth C. Kolb +19 more
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TLDR
A highly selective positron emission tomography (PET) imaging agent targeting PHF‐tau in human Alzheimer's disease (AD) brains is developed.Abstract:
Objective We wished to develop a highly selective positron emission tomography (PET) imaging agent targeting PHF-tau in human Alzheimer's disease (AD) brains. Methods To screen potential tau binders, human AD brain sections were used as a source of native paired helical filament (PHF)-tau and Aβ rather than synthetic tau aggregates or Aβ fibrils generated in vitro to measure the affinity and selectivity of [ 18 F]T807 to tau and Aβ. Brain uptake and biodistribution of [ 18 F]T807 in mice were also tested. Results In vitro autoradiography results show that [ 18 F]T807 exhibits strong binding to PHF-tau-positive human brain sections. A dissociation constant ( K d ) of [ 18 F]T807 (14.6 nM) was measured using brain sections from the frontal lobe of AD patients. A comparison of autoradiography and double immunohistochemical staining of PHF-tau and Aβ on adjacent sections demonstrated that [ 18 F]T807 binding colocalized with immunoreactive PHF-tau pathology, but did not highlight Aβ plaques. In vivo studies in mice demonstrated that [ 18 F]T807 was able to cross the blood–brain barrier and washed out quickly. Conclusions [ 18 F]T807 demonstrates high affinity and selectivity to PHF-tau as well as favorable in vivo properties, making this a promising candidate as an imaging agent for AD.read more
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Journal ArticleDOI
Preclinical Alzheimer's disease: Definition, natural history, and diagnostic criteria.
Bruno Dubois,Harald Hampel,Harald Hampel,Howard Feldman,Philip Scheltens,Paul S. Aisen,Sandrine Andrieu,Hovagim Bakardjian,Habib Benali,Lars Bertram,Lars Bertram,Kaj Blennow,Karl Broich,Enrica Cavedo,Sebastian J. Crutch,Jean-François Dartigues,Charles Duyckaerts,Stéphane Epelbaum,Giovanni B. Frisoni,Serge Gauthier,Remy Genthon,Alida A. Gouw,Alida A. Gouw,Marie-Odile Habert,David M. Holtzman,Miia Kivipelto,Miia Kivipelto,Simone Lista,José Luis Molinuevo,Sid E. O'Bryant,Gil D. Rabinovici,Christopher C. Rowe,Stephen Salloway,Lon S. Schneider,Reisa A. Sperling,Reisa A. Sperling,Marc Teichmann,Maria C. Carrillo,Jeffrey L. Cummings,Cliff R. Jack +39 more
TL;DR: An updated review of the literature and evidence on the definitions and lexicon, the limits, the natural history, the markers of progression, and the ethical consequence of detecting the disease at this asymptomatic stage of Alzheimer's disease are provided.
Journal ArticleDOI
PET Imaging of Tau Deposition in the Aging Human Brain
Michael Schöll,Michael Schöll,Samuel N. Lockhart,Daniel R. Schonhaut,James P. O'Neil,Mustafa Janabi,Rik Ossenkoppele,Rik Ossenkoppele,Rik Ossenkoppele,Suzanne L. Baker,Jacob W. Vogel,Jamie Faria,Henry Schwimmer,Gil D. Rabinovici,Gil D. Rabinovici,Gil D. Rabinovici,William J. Jagust,William J. Jagust +17 more
TL;DR: In this paper, the authors defined patterns of tau tracer retention in normal aging in relation to age, cognition, and β-amyloid deposition, and found that older age was associated with increased tracers retention in regions of the medial temporal lobe, which predicted worse episodic memory performance.
Journal ArticleDOI
Tau PET patterns mirror clinical and neuroanatomical variability in Alzheimer's disease.
Rik Ossenkoppele,Rik Ossenkoppele,Rik Ossenkoppele,Daniel R. Schonhaut,Daniel R. Schonhaut,Michael Schöll,Michael Schöll,Samuel N. Lockhart,Nagehan Ayakta,Nagehan Ayakta,Suzanne L. Baker,James P. O'Neil,Mustafa Janabi,Andreas Lazaris,Averill Cantwell,Jacob W. Vogel,Miguel Santos,Zachary A. Miller,Brianne M. Bettcher,Brianne M. Bettcher,Keith A. Vossel,Joel H. Kramer,Maria Luisa Gorno-Tempini,Bruce L. Miller,William J. Jagust,William J. Jagust,Gil D. Rabinovici,Gil D. Rabinovici +27 more
TL;DR: Results are consistent with and expand upon findings from post-mortem, animal and cerebrospinal fluid studies, and suggest that the pathological aggregation of tau is closely linked to patterns of neurodegeneration and clinical manifestations of Alzheimer's disease.
Journal ArticleDOI
Tau positron emission tomographic imaging in aging and early Alzheimer disease
Keith A. Johnson,Aaron P. Schultz,Rebecca A. Betensky,J. Alex Becker,Jorge Sepulcre,Dorene M. Rentz,Dorene M. Rentz,Elizabeth C. Mormino,Jasmeer P. Chhatwal,Jasmeer P. Chhatwal,Rebecca E. Amariglio,Rebecca E. Amariglio,Kate V. Papp,Kate V. Papp,Gad A. Marshall,Gad A. Marshall,Mark W. Albers,Samantha Mauro,Lesley C. Pepin,Jonathan Alverio,Kelly Judge,Marlie Philiossaint,Timothy M. Shoup,Daniel Yokell,Bradford C. Dickerson,Teresa Gomez-Isla,Bradley T. Hyman,Neil Vasdev,Reisa A. Sperling +28 more
TL;DR: Detection of focal brain tau deposition during life could greatly facilitate accurate diagnosis of Alzheimer disease (AD), staging and monitoring of disease progression, and development of disease‐modifying therapies.
Journal ArticleDOI
The Evolution of Preclinical Alzheimer’s Disease: Implications for Prevention Trials
TL;DR: Recent progress in cognitive, imaging, and biomarker outcomes in the field of preclinical Alzheimer's disease, and the remaining gaps in knowledge are highlighted.
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