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While the major focus of antibody-based therapy development was on A\u03b2, arguably with limited success in clinical trials, targeting tau has become an emerging strategy, possibly extending therapies to dementias with isolated tau pathology. Interestingly, low titres of autoantibodies to pathological tau have been described in humans and transgenic mouse models, but their pathophysiological relevance remained elusive. Here, we used two independent approaches to deplete the B-cell lineage and hence antibody formation in human P301S mutant tau transgenic mice, TAU58\/2. TAU58\/2 mice were either crossed with the B-cell-deficient <jats:italic>Ighm<\/jats:italic> knockout line (muMT<jats:sup>\u2212\/\u2212<\/jats:sup>) or treated with anti-CD20 antibodies that target B-cell precursors. In both models, B-cell depletion significantly reduced astrocytosis in TAU58\/2 mice. Only when B-cells were absent throughout life, in TAU58\/2.muMT<jats:sup>\u2212\/\u2212<\/jats:sup> mice, were spatial learning deficits moderately aggravated while motor performance improved as compared to B-cell-competent TAU58\/2 mice. This was associated with changes in brain region-specific tau solubility. No other relevant behavioural or neuropathological changes were observed in TAU58\/2 mice in the absence of B-cells\/antibodies. Taken together, our data suggests that the presence of antibodies throughout life contributes to astrocytosis in TAU58\/2 mice and limits learning deficits, while other deficits and neuropathological changes appear to be independent of the presence of B-cells\/antibodies.<\/jats:p>","DOI":"10.1038\/s41598-020-70845-x","type":"journal-article","created":{"date-parts":[[2020,8,14]],"date-time":"2020-08-14T12:27:09Z","timestamp":1597408029000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Contribution of endogenous antibodies to learning deficits and astrocytosis in human P301S mutant tau transgenic mice"],"prefix":"10.1038","volume":"10","author":[{"given":"Julia","family":"van der Hoven","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annika","family":"van Hummel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Przybyla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prita R.","family":"Asih","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehul","family":"Gajwani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Astrid F.","family":"Feiten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yazi D.","family":"Ke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arne","family":"Ittner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet","family":"van Eersel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars M.","family":"Ittner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,8,14]]},"reference":[{"key":"70845_CR1","volume-title":"World Alzheimer Report 2015: The Global Impact of Dementia: An Analysis of Prevalence, Incidence, Cost and Trends","author":"MJ Prince","year":"2015","unstructured":"Prince, M. 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