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Abstract
The cellular prion protein (PrPC) plays many roles in the developing and adult brain. In addition, PrPC binds to several amyloids in oligomeric and prefibrillar forms and may act as a putative receptor of abnormal misfolded protein species. The role of PrPC in tau seeding and spreading is not known. In the present study, we have inoculated well-characterized sarkosyl-insoluble fractions of sporadic Alzheimer’s disease (sAD) into the brain of adult wild-type mice (Prnp+/+), Prnp0/0 (ZH3 strain) mice, and mice over-expressing the secreted form of PrPC lacking their GPI anchor (Tg44 strain). Phospho-tau (ptau) seeding and spreading involving neurons and oligodendrocytes were observed three and six months after inoculation. 3Rtau and 4Rtau deposits from the host tau, as revealed by inoculating Mapt0/0 mice and by using specific anti-mouse and anti-human tau antibodies suggest modulation of exon 10 splicing of the host mouse Mapt gene elicited by exogenous sAD-tau. However, no tau seeding and spreading differences were observed among Prnp genotypes. Our results show that PrPC does not affect tau seeding and spreading in vivo.
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1 Institute for Bioengineering of Catalonia (IBEC), Molecular and Cellular Neurobiotechnology, Barcelona, Spain (GRID:grid.424736.0) (ISNI:0000 0004 0536 2369); University of Barcelona, Department of Cell Biology, Physiology and Immunology, Faculty of Biology, Barcelona, Spain (GRID:grid.5841.8) (ISNI:0000 0004 1937 0247); Institute of Health Carlos III, Ciberned (Network Centre of Biomedical Research of Neurodegenerative Diseases), Madrid, Spain (GRID:grid.413448.e) (ISNI:0000 0000 9314 1427); University of Barcelona, Institute of Neuroscience, Barcelona, Spain (GRID:grid.5841.8) (ISNI:0000 0004 1937 0247); University of California Santa Barbara, Neuroscience Research Institute and Molecular, Cell and Developmental Biology, Santa Barbara, USA (GRID:grid.133342.4) (ISNI:0000 0004 1936 9676)
2 Institute for Bioengineering of Catalonia (IBEC), Molecular and Cellular Neurobiotechnology, Barcelona, Spain (GRID:grid.424736.0) (ISNI:0000 0004 0536 2369); University of Barcelona, Department of Cell Biology, Physiology and Immunology, Faculty of Biology, Barcelona, Spain (GRID:grid.5841.8) (ISNI:0000 0004 1937 0247); Institute of Health Carlos III, Ciberned (Network Centre of Biomedical Research of Neurodegenerative Diseases), Madrid, Spain (GRID:grid.413448.e) (ISNI:0000 0000 9314 1427); University of Barcelona, Institute of Neuroscience, Barcelona, Spain (GRID:grid.5841.8) (ISNI:0000 0004 1937 0247)
3 Institute of Health Carlos III, Ciberned (Network Centre of Biomedical Research of Neurodegenerative Diseases), Madrid, Spain (GRID:grid.413448.e) (ISNI:0000 0000 9314 1427); Bellvitge University Hospital-IDIBELL, Hospitalet de Llobregat, Department of Pathology and Experimental Therapeutics, University of Barcelona, Barcelona, Spain (GRID:grid.411129.e) (ISNI:0000 0000 8836 0780)
4 Institute of Health Carlos III, Ciberned (Network Centre of Biomedical Research of Neurodegenerative Diseases), Madrid, Spain (GRID:grid.413448.e) (ISNI:0000 0000 9314 1427); Centro de Biología Molecular ‘Severo Ochoa’ (CBMSO) CSIC/UAM, Madrid, Spain (GRID:grid.465524.4)
5 Institute of Health Carlos III, Ciberned (Network Centre of Biomedical Research of Neurodegenerative Diseases), Madrid, Spain (GRID:grid.413448.e) (ISNI:0000 0000 9314 1427); Universidad de Navarra, Department of Neurosciences, Center for Applied Medical Research (CIMA), Pamplona, Spain (GRID:grid.5924.a) (ISNI:0000 0004 1937 0271)
6 University of Zurich, Institute of Neuropathology, Zurich, Switzerland (GRID:grid.7400.3) (ISNI:0000 0004 1937 0650)
7 University of Pavia, Amyloidosis Research and Treatment Center, Foundation Scientific Institute Policlinico San Matteo, Department of Molecular Medicine, Pavia, Italy (GRID:grid.8982.b) (ISNI:0000 0004 1762 5736)