The cellular prion protein does not affect tau seeding and spreading of sarkosyl-insoluble fractions from Alzheimer’s disease
The cellular prion protein (PrP<sup>C</sup>) plays many roles in the developing and adult brain. In addition, PrP<sup>C</sup> binds to several amyloids in oligomeric and prefibrillar forms and may act as a putative receptor of abnormal misfolded protein species. The role of PrP<sup>C</sup> 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<sup>+/+</sup>), Prnp<sup>0/0</sup> (ZH3 strain) mice, and mice over-expressing the secreted form of PrP<sup>C</sup> 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 Mapt<sup>0/0</sup> 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 PrP<sup>C</sup> does not affect tau seeding and spreading in vivo.
Authors
- Julia Sala‐Jarque (ORCID: https://orcid.org/0000-0002-9103-7305)
- Rosalina Gavı́n (ORCID: https://orcid.org/0000-0003-1982-2162)
- Mario Nuvolone (ORCID: https://orcid.org/0000-0001-8334-1684)
- Isidró Ferrer (ORCID: https://orcid.org/0000-0001-9888-8754)
- Adriano Aguzzi (ORCID: https://orcid.org/0000-0002-0344-6708)
- José Antonio del Rı́o (ORCID: https://orcid.org/0000-0002-5214-4909)
- Pol Andrés‐Benito (ORCID: https://orcid.org/0000-0003-3000-0338)
- Vanessa Gil (ORCID: https://orcid.org/0000-0002-7782-5575)
- Pol Picón-Pagès (ORCID: https://orcid.org/0000-0002-6471-3072)
- José Luis Lanciego (ORCID: https://orcid.org/0000-0003-2301-5419)
- Félix Hernández (ORCID: https://orcid.org/0000-0001-8753-8249)
- Jesús Ávila (ORCID: https://orcid.org/0000-0002-6288-0571)
- Inés Martínez-Soria
Institutions
- University of California, Santa Barbara (US)
- University of Zurich (CH)
- University of Pavia (IT)
- Bellvitge University Hospital (ES)
- Biomedical Research Networking Center on Neurodegenerative Diseases (ES)
- Centro de Biología Molecular Severo Ochoa (ES)
- Institute for Bioengineering of Catalonia (ES)
- Universidad Autónoma de Madrid (ES)
- Universitat de Barcelona (ES)
- Universidad de Navarra (ES)
Publication Details
- Journal
- Scientific Reports
- Published
- 2024-09-16
- DOI
- https://doi.org/10.1038/s41598-024-72232-2
- Primary Topic
- Prion Diseases and Protein Misfolding
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- “la Caixa” Foundation
- Ministerio de Ciencia e Innovación
- Fundación Tatiana Pérez de Guzmán el Bueno
- Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas
- Agència de Gestió d'Ajuts Universitaris i de Recerca