The cellular prion protein does not affect tau seeding and spreading of sarkosyl-insoluble fractions from Alzheimer's disease

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....

Descripción completa

Detalles Bibliográficos
Autores: Sala-Jarque, Julia, Gil, Vanessa, Andrés-Benito, Pol, Martínez-Soria, Inés, Picón-Pagès, Pol, Ávila, Jesús, Lanciego, José Luis, Nuvolone, Mario, Aguzzi, Adriano, Gavín, Rosalina, Ferrer, Isidro, del Rio, Jose Antonio, Hernández Pérez, Félix
Tipo de recurso: artículo
Fecha de publicación:2024
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/717481
Acceso en línea:http://hdl.handle.net/10486/717481
https://dx.doi.org/10.1038/s41598-024-72232-2
Access Level:acceso abierto
Palabra clave:PrPC
Prnp
Tau
Mapt
alzheimer’s disease
seeding
spreading
Biología y Biomedicina / Biología
Descripción
Sumario: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