Abstract | OBJECTIVE: 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. METHODS: RESULTS: 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. INTERPRETATION: 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.
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Authors | Marta Marquié, Marc D Normandin, Charles R Vanderburg, Isabel M Costantino, Elizabeth A Bien, Lisa G Rycyna, William E Klunk, Chester A Mathis, Milos D Ikonomovic, Manik L Debnath, Neil Vasdev, Bradford C Dickerson, Stephen N Gomperts, John H Growdon, Keith A Johnson, Matthew P Frosch, Bradley T Hyman, Teresa Gómez-Isla |
Journal | Annals of neurology
(Ann Neurol)
Vol. 78
Issue 5
Pg. 787-800
(Nov 2015)
ISSN: 1531-8249 [Electronic] United States |
PMID | 26344059
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Copyright | © 2015 American Neurological Association. |
Chemical References |
- Amyloid
- Carbolines
- Radiopharmaceuticals
- tau Proteins
- 7-(6-fluoropyridin-3-yl)-5H-pyrido(4,3-b)indole
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Topics |
- Aged
- Aged, 80 and over
- Alzheimer Disease
(diagnostic imaging)
- Amyloid
(metabolism)
- Autoradiography
- Brain
(diagnostic imaging)
- Cadaver
- Carbolines
- Dementia
(diagnostic imaging)
- Female
- Frontotemporal Lobar Degeneration
(diagnostic imaging)
- Humans
- Inclusion Bodies
(diagnostic imaging)
- Intracranial Hemorrhages
(diagnostic imaging)
- Male
- Middle Aged
- Positron-Emission Tomography
- Radiopharmaceuticals
- TDP-43 Proteinopathies
(diagnostic imaging)
- Tauopathies
(diagnostic imaging)
- tau Proteins
(metabolism)
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