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.

Keywords: Alzheimer’s disease; BODIPY; near-infrared fluorescent probes; neurodegeneration; super-resolution imaging; tau; tauopathies.

Figure 1

Stochastic optical reconstruction microscopy (STORM) image of beta-amyloid plaque and neurofibrillary tangles (NFT) in Alzheimer’s disease (AD) patient brain slice. (A) Confocal microscopy image of beta-amyloid aggregates (in red) and neuro-fibrillary tangles (A1) from an AD patient brain specimen. Super-imposed images are shown in panel (A2). Same senile plaque as in panel (A), imaged by combining fluorescence microscopy for beta-amyloid aggregate (B) with STORM microscopy for NFT (B1). Super-imposed images are shown in panel (B2). Note the difference in resolution between image in panels (A2) and (B2). Modified from Codron et al. (2020) under the Creative Commons CC-BY-NC-ND.

Figure 2

4,4-difluoro-4-bora3a,4a-diaza-s-indacene (BODIPY)-based probe binds to neurofibrillary tangles in a mouse model of AD. (A) Near-infrared probes (NIR) Tau 1&2 bind to NFT structures. (B) Immunostaining showing the colocalization between pTau (green signal) and Tau1 (red signal) in the CA1 (upper panels) and CA3 (lower panels) hippocampal region of a mouse treated with okadaic acid. Colocalization of the two signals is shown. Adapted with permission from Verwilst et al. (2017). Copyright 2017 American Chemical Society.