Looking for the link between plaques and tangles

Abstract

We wished to develop a highly selective positron emission tomography (PET) imaging agent targeting PHF-tau in human Alzheimer's disease (AD) brains.To screen potential tau binders, human AD brain sections were used as a source of native paired helical filament (PHF)-tau and Aβ rather than synthetic tau aggregates or Aβ fibrils generated in vitro to measure the affinity and selectivity of [18F]T807 to tau and Aβ. Brain uptake and biodistribution of [18F]T807 in mice were also tested.In vitro autoradiography results show that [18F]T807 exhibits strong binding to PHF-tau-positive human brain sections. A dissociation constant (Kd) of [18F]T807 (14.6 nM) was measured using brain sections from the frontal lobe of AD patients. A comparison of autoradiography and double immunohistochemical staining of PHF-tau and Aβ on adjacent sections demonstrated that [18F]T807 binding colocalized with immunoreactive PHF-tau pathology, but did not highlight Aβ plaques. In vivo studies in mice demonstrated that [18F]T807 was able to cross the blood–brain barrier and washed out quickly.[18F]T807 demonstrates high affinity and selectivity to PHF-tau as well as favorable in vivo properties, making this a promising candidate as an imaging agent for AD.