[f3–07–02]: tau immunotherapy prevents the spread and promotes the clearance of pathology in mice

In Alzheimer's disease (AD) all six isoforms of tau are abnormally hyperphosphorylated. Tau pathology in the absence of Abeta pathology is a hallmark of a family of neurodegenerative disorders, called tauopathies. Without exception tau pathology is made up of hyperphosphorylated protein. Given the involvement of six isoforms there are multiple possible patterns of tau hyperphosphorylation. Unlike normal tau which binds to microtubule protein subunit tubulin and promotes its assembly and stabilizes the microtubule network, the ptau instead binds to normal tau and templates it in a prion-like fashion into tau oligomers and filaments. We took advantage of this finding and carried out immunization with tau antibodies 43D against tau6–18 and 77E9 against tau184–195, targeting the amino-terminal domains of tau in 3xTg-AD mouse model of AD and frontotemporal dementia. We found that with this strategy we can rescue not only tau but also Abeta pathology and cognitive impairment in 3xTg-AD mice. Furthermore, we found that the immunotherapy can also prevent the spread of AD-ptau induced pathology in tau transgenic mice. Immunization targeting the amino-terminal domain of tau has the potential to lead to an effective disease modifying treatment for AD and related tauopathies.