Molecular Imaging of Tau Protein: New Insights and Future Directions

Abstract

Tau is a microtubule-associated protein (MAPT) that is highly expressed in neurons and implicated in several cellular processes. Tau misfolding and self-aggregation give rise to proteinaceous deposits known as neuro-fibrillary tangles. Tau tangles play a key role in the genesis of a group of diseases commonly referred to as tauopathies; notably, these aggregates start to form decades before any clinical symptoms manifest. Advanced imaging methodologies have clarified important structural and functional aspects of tau and could have a role as diagnostic tools in clinical research. In the present review, recent progresses in tau imaging will be discussed. We will focus mainly on super-resolution imaging methods and the development of near-infrared fluorescent probes.

Rational Design and Synthesis of a Novel BODIPY-based Probe for Selective Imaging of Tau Tangles in Human iPSC-derived Cortical Neurons

“…Thus, the need for non-toxic uorescence dyes bearing better selectivity, a nity, and speci city for tau proteins is fostering the development of a novel generation of tracers 25,26 . In this regard, the recent characterization of tau protein structure at the atomic 27,28 might represent an outstanding milestone for better tackling such needs 29 .…”

Revisiting the grammar of Tau aggregation and pathology formation: how new insights from brain pathology are shaping how we study and target Tauopathies

“…19,21 These studies have enabled structure based classification of Tauopathies, thus paving the way for a rational design of disease-specific therapeutics and and diagnostics. 575 Recently, Cryo-EM was used to directly map the ligand-binding sites within the AD Tau fold. 576 It showed that fibril core residues in multiple diseases primarily comprise the MTBR repeats R3 and R4, which is important in designing the antibodies with epitopes directed outside of these regions.…”

Ferritin nanocage-enabled detection of pathological tau in living human retinal cells

“…In all clinical trials on AD, inclusion criteria from patient enrollment to concluding evaluation at the end of the study, require careful evaluation of suitable biomarkers 4 . MRI is the most common entry-level analysis collected as an outcome measure, followed by amyloid PET and tau PET 4 – 6 . The current trend for novel clinical trials, however, increasingly requires advances in ultra-sensitive methods to detect proteins in cerebrospinal fluid (CSF) and plasma that enable the identification of pathological changes along the AD continuum.…”