Moscoso, Alexis;
Wren, Melissa C;
Lashley, Tammaryn;
Arstad, Erik;
Murray, Melissa E;
Fox, Nick C;
Sander, Kerstin;
(2022)
Imaging tau pathology in Alzheimer's disease with positron emission tomography: lessons learned from imaging-neuropathology validation studies.
Molecular Neurodegeneration
, 17
(1)
, Article 39. 10.1186/s13024-022-00543-x.
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Abstract
Though the presence of both amyloid-β (Aβ) plaques and tau neurofibrillary tangles is necessary for neuropathologic diagnosis of Alzheimer’s disease (AD), it is now widely recognized that tau burden correlates more strongly with neurodegeneration and cognitive impairment in life than the development of Aβ plaques [1]. Recent developments of tau-sensitive radiotracers for imaging with positron emission tomography (PET) have, for the first time, enabled visualisation, mapping, and quantification of inclusions of aggregated, paired helical filament (PHF) tau associated with AD in the living brain [2]. In-depth characterisation of tau PET tracers, and in particular comparison of antemortem PET readings with postmortem neuropathologic findings, were of paramount importance to understand the clinical potential and limitations of the new imaging tools. In the case of [18F]flortaucipir, the most widely used tau PET ligand, these cross-validation studies, together with autoradiography evaluations, provided information about the specificity of this tracer to PHF-tau in AD but also revealed substantial undesired (off-target) binding and limited ability to detect PHF-tau at the earliest Braak stages [3,4,5,6,7]. The combined data subsequently underpinned the implementation of an effective method for the clinical interpretation of [18F]flortaucipir PET scans [3]. Ultimately, these efforts have led to the approval of [(18)^F]flortaucipir by the US Food and Drug Administration (FDA) as the first PET radiopharmaceutical indicated to ‘estimate the density and distribution of aggregated neurofibrillary tangles in patients with cognitive impairment who are being evaluated for AD (Tauvid prescribing information, https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/212123s000lbl.pdf).
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