A novel in vivo model of tau propagation with rapid and progressive neurofibrillary tangle pathology: the pattern of spread is determined by connectivity, not proximity

• DOI: 10.1007/s00401-014-1254-6
• Publication Date: 2014-02-17T15:16:21Z
• Authors: Zeshan Ahmed; Jane Cooper; Tracey K. Murray; Katya Garn; Emily McNaughton; Hannah Clarke; Samira Parhizkar; Mark A. Ward; Annalisa Cavallini; Samuel Jackson; Suchira Bose; Florence Clavaguera; Markus Tolnay; Isabelle Lavenir; Michel Goedert; Michael L. Hutton; Michael J. O’Neill
• Keywords: Tangle; Tau Pathology; Neurofibrillary tangle; Tauopathy; Tau protein; Corticobasal degeneration

Abstract Intracellular inclusions composed of hyperphosphorylated filamentous tau are a hallmark Alzheimer’s disease, progressive supranuclear palsy, Pick’s disease and other sporadic neurodegenerative tauopathies. Recent in vitro vivo studies have shown that aggregates do not only seed further aggregation within neurons, but can also spread to neighbouring cells functionally connected brain regions. This process is referred as ‘tau propagation’ may explain the stereotypic progression pathology brains patients. Here, we describe novel model propagation using human P301S transgenic mice infused unilaterally with extract containing aggregates. Infusion-related neurofibrillary tangle was first observed 2 weeks post-infusion increased stereotypic, time-dependent manner. Contralateral anterior/posterior evident nuclei strong synaptic connections (efferent afferent) site infusion, indicating dependent on connectivity rather than spatial proximity. notion supported by infusion-related white matter tracts interconnect these The rapid robust this will be valuable for both basic research drug discovery process.