An autoradiographic evaluation of AV-1451 Tau PET in dementia

作者：Lowe, Val J.^*; Curran, Geoffry; Fang, Ping; Liesinger, Amanda M.; Josephs, Keith A.; Parisi, Joseph E.; Kantarci, Kejal; Boeve, Bradley F.; Pandey, Mukesh K.; Bruinsma, Tyler; Knopman, David S.; Jones, David T.; Petrucelli, Leonard; Cook, Casey N.; Graff-Radford, Neill R.; Dickson, Dennis W.; Petersen, Ronald C.; Jack, Clifford R., Jr.; Murray, Melissa E.

来源：Acta Neuropathologica Communications, 2016, 4(1): 58.

DOI：10.1186/s40478-016-0315-6

• AV-1451
• Tau
• Alzheimer's disease
• TDP-43
• Pick Disease
• Corticobasal degeneration
• Progressive supranuclear palsy
• Tauopathy
• Pick's disease
• Atypical Alzheimer's disease
• Frontotemporal dementia

Background: It is essential to determine the specificity of AV-1451 PET for tau in brain imaging by using pathological comparisons. We performed autoradiography in autopsy-confirmed Alzheimer disease and other neurodegenerative disorders to evaluate the specificity of AV-1451 binding for tau aggregates. @@@ Methods: Tissue samples were selected that had a variety of dementia-related neuropathologies including Alzheimer disease, primary age-related tauopathy, tangle predominant dementia, non-Alzheimer disease tauopathies, frontotemporal dementia, parkinsonism, Lewy body disease and multiple system atrophy (n = 38). Brain tissue sections were stained for tau, TAR DNA-binding protein-43, and alpha-synuclein and compared to AV-1451 autoradiography on adjacent sections. @@@ Results: AV-1451 preferentially localized to neurofibrillary tangles, with less binding to areas enriched in neuritic pathology and less mature tau. The strength of AV-1451 binding with respect to tau isoforms in various neurodegenerative disorders was: 3R + 4R tau (e.g., AD) > 3R tau (e.g., Pick disease) or 4R tau. Only minimal binding of AV-1451 to TAR DNA-binding protein-43 positive regions was detected. No binding of AV-1451 to a-synuclein was detected. "Off-target" binding was seen in vessels, iron-associated regions, substantia nigra, calcifications in the choroid plexus, and leptomeningeal melanin. @@@ Conclusions: Reduced AV-1451 binding in neuritic pathology compared to neurofibrillary tangles suggests that the maturity of tau pathology may affect AV-1451 binding and suggests complexity in AV-1451 binding. Poor association of AV-1451 with tauopathies that have preferential accumulation of either 4R tau or 3R tau suggests limited clinical utility in detecting these pathologies. In contrast, for disorders associated with 3R + 4R tau, such as Alzheimer disease, AV-1451 binds tau avidly but does not completely reflect the early stage tau progression suggested by Braak neurofibrillary tangle staging. AV-1451 binding to TAR DNA-binding protein-43 or TAR DNA-binding protein-43 positive regions can be weakly positive. Clinical use of AV-1451 will require a familiarity with distinct types of "off-target" binding.

• 出版日期2016-6-13