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- Title
Validating novel tau positron emission tomography tracer [F-18]-AV-1451 (T807) on postmortem brain tissue.
- Authors
Marquié, Marta; Normandin, Marc D.; Vanderburg, Charles R.; Costantino, Isabel M.; Bien, Elizabeth A.; Rycyna, Lisa G.; Klunk, William E.; Mathis, Chester A.; Ikonomovic, Milos D.; Debnath, Manik L.; Vasdev, Neil; Dickerson, Bradford C.; Gomperts, Stephen N.; Growdon, John H.; Johnson, Keith A.; Frosch, Matthew P.; Hyman, Bradley T.; Gómez‐Isla, Teresa
- Abstract
<bold>Objective: </bold>To examine region- and substrate-specific autoradiographic and in vitro binding patterns of positron emission tomography tracer [F-18]-AV-1451 (previously known as T807), tailored to allow in vivo detection of paired helical filament-tau-containing lesions, and to determine whether there is off-target binding to other amyloid/non-amyloid proteins.<bold>Methods: </bold>We applied [F-18]-AV-1451 phosphor screen autoradiography, [F-18]-AV-1451 nuclear emulsion autoradiography, and [H-3]-AV-1451 in vitro binding assays to the study of postmortem samples from patients with a definite pathological diagnosis of Alzheimer disease, frontotemporal lobar degeneration-tau, frontotemporal lobar degeneration-transactive response DNA binding protein 43 (TDP-43), progressive supranuclear palsy, corticobasal degeneration, dementia with Lewy bodies, multiple system atrophy, cerebral amyloid angiopathy and elderly controls free of pathology.<bold>Results: </bold>Our data suggest that [F-18]-AV-1451 strongly binds to tau lesions primarily made of paired helical filaments in Alzheimer brains (eg, intraneuronal and extraneuronal tangles and dystrophic neurites), but does not seem to bind to a significant extent to neuronal and glial inclusions mainly composed of straight tau filaments in non-Alzheimer tauopathy brains or to lesions containing β-amyloid, α-synuclein, or TDP-43. [F-18]-AV-1451 off-target binding to neuromelanin- and melanin-containing cells and, to a lesser extent, to brain hemorrhagic lesions was identified.<bold>Interpretation: </bold>Our data suggest that [F-18]-AV-1451 holds promise as a surrogate marker for the detection of brain tau pathology in the form of tangles and paired helical filament-tau-containing neurites in Alzheimer brains but also point to its relatively lower affinity for lesions primarily made of straight tau filaments in non-Alzheimer tauopathy cases and to the existence of some [F-18]-AV-1451 off-target binding. These findings provide important insights for interpreting in vivo patterns of [F-18]-AV-1451 retention.
- Subjects
BRAIN; PROTEIN metabolism; ALZHEIMER'S disease; CEREBRAL hemorrhage; CELLS; DEAD; DEMENTIA; NERVE tissue proteins; NEURODEGENERATION; PYRIDINE; RADIOGRAPHY; RADIOPHARMACEUTICALS; RESEARCH funding; POSITRON emission tomography; FRONTOTEMPORAL lobar degeneration; TDP-43 proteinopathies
- Publication
Annals of Neurology, 2015, Vol 78, Issue 5, p787
- ISSN
0364-5134
- Publication type
journal article
- DOI
10.1002/ana.24517