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In Alzheimer’s disease, neurofibrillary tangle pathology appears to spread along neuronal connections, proposed to be mediated by the release and uptake of abnormal, disease-specific forms of microtubule-binding protein tau MAPT. It is currently unclear whether transfer of tau between neurons is a toxic gain-of-function process in dementia or reflects a constitutive biological process. We report two entry mechanisms for monomeric tau to human neurons: a rapid dynamin-dependent phase typical of endocytosis and a second, slower actin-dependent phase of macropinocytosis. Aggregated tau entry is independent of actin polymerization and largely dynamin dependent, consistent with endocytosis and distinct from macropinocytosis, the major route for aggregated tau entry reported for non-neuronal cells. Anti-tau antibodies abrogate monomeric tau entry into neurons, but less efficiently in the case of aggregated tau, where internalized tau carries antibody with it into neurons. These data suggest that tau entry to human neurons is a physiological process and not a disease-specific phenomenon.

More information Original publication

DOI

10.1016/j.celrep.2018.03.021

Type

Journal article

Publisher

Cell Reports

Publication Date

3/2018

Volume

22

Pages

3612 - 3624

Addresses

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5896171/

Keywords

Alzheimer’s diseasefrontotemporal dementiaTauMAPTiPSCendocytosishuman neuronsintracellular transport