[F-18]-AV-1451 binding correlates with postmortem neurofibrillary tangle Braak staging
| Autor: | Marc D. Normandin, Matthew P. Frosch, Prianca Ramanan, Ana C. Amaral, Eline E. Verwer, Teresa Gomez-Isla, Michael Siao Tick Chong, Jose J. Gonzalez, Nil Sáez-Calveras, Alejandro Antón-Fernández, Avery C. Meltzer, Marta Marquié |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Pathology medicine.medical_specialty Blotting Western Enzyme-Linked Immunosorbent Assay Plaque Amyloid tau Proteins Severity of Illness Index Article Pathology and Forensic Medicine White matter 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine mental disorders Medicine Dementia Humans Phosphorylation Aged Aged 80 and over business.industry Brain Neurofibrillary tangle Neurofibrillary Tangles Middle Aged medicine.disease Entorhinal cortex Immunohistochemistry 030104 developmental biology medicine.anatomical_structure Visual cortex Biomarker (medicine) Autoradiography Female Neurology (clinical) Radiopharmaceuticals business 030217 neurology & neurosurgery Immunostaining Braak staging Carbolines |
| Zdroj: | Acta neuropathologica. 134(4) |
| ISSN: | 1432-0533 |
| Popis: | [F-18]-AV-1451, a PET tracer specifically developed to detect brain neurofibrillary tau pathology, has the potential to facilitate accurate diagnosis of Alzheimer’s disease (AD), staging of brain tau burden and monitoring disease progression. Recent PET studies show that patients with mild cognitive impairment and AD dementia exhibit significantly higher in vivo [F-18]-AV-1451 retention than cognitively normal controls. Importantly, PET patterns of [F-18]-AV-1451 correlate well with disease severity and seem to match the predicted topographic Braak staging of neurofibrillary tangles (NFTs) in AD, although this awaits confirmation. We studied the correlation of autoradiographic binding patterns of [F-18]-AV-1451 and the stereotypical spatiotemporal pattern of progression of NFTs using legacy postmortem brain samples representing different Braak NFT stages (I-VI). We performed [F-18]-AV-1451 phosphor-screen autoradiography and quantitative tau measurements (stereologically based NFT counts and biochemical analysis of tau pathology) in three brain regions (entorhinal cortex, superior temporal sulcus and visual cortex) in a total of 22 cases: low Braak (I–II, n = 6), intermediate Braak (III–IV, n = 7) and high Braak (V–VI, n = 9). Strong and selective [F-18]-AV-1451 binding was detected in all tangle-containing regions matching precisely the observed pattern of PHF-tau immunostaining across the different Braak stages. As expected, no signal was detected in the white matter or other non-tangle containing regions. Quantification of [F-18]-AV-1451 binding was very significantly correlated with the number of NFTs present in each brain region and with the total tau and phospho-tau content as reported by Western blot and ELISA. [F-18]-AV-1451 is a promising biomarker for in vivo quantification of brain tau burden in AD. Neuroimaging–pathologic studies conducted on postmortem material from individuals imaged while alive are now needed to confirm these observations. |
| Databáze: | OpenAIRE |
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