Your browser doesn't support javascript.
loading
Conclusive demonstration of iatrogenic Alzheimer's disease transmission in a model of stem cell transplantation.
Singh, Chaahat S B; Johns, Kelly Marie; Kari, Suresh; Munro, Lonna; Mathews, Angela; Fenninger, Franz; Pfeifer, Cheryl G; Jefferies, Wilfred A.
Afiliación
  • Singh CSB; Michael Smith Laboratories, University of British Columbia, 2185 East Mall, Vancouver, BC V6T 1Z4, Canada; The Vancouver Prostate Centre, Vancouver General Hospital, 2660 Oak Street, Vancouver, BC V6H 3Z6, Canada; Centre for Blood Research, University of British Columbia, 2350 Health Sciences Mall,
  • Johns KM; Michael Smith Laboratories, University of British Columbia, 2185 East Mall, Vancouver, BC V6T 1Z4, Canada; The Vancouver Prostate Centre, Vancouver General Hospital, 2660 Oak Street, Vancouver, BC V6H 3Z6, Canada; Centre for Blood Research, University of British Columbia, 2350 Health Sciences Mall,
  • Kari S; Michael Smith Laboratories, University of British Columbia, 2185 East Mall, Vancouver, BC V6T 1Z4, Canada; The Vancouver Prostate Centre, Vancouver General Hospital, 2660 Oak Street, Vancouver, BC V6H 3Z6, Canada; Centre for Blood Research, University of British Columbia, 2350 Health Sciences Mall,
  • Munro L; Michael Smith Laboratories, University of British Columbia, 2185 East Mall, Vancouver, BC V6T 1Z4, Canada; The Vancouver Prostate Centre, Vancouver General Hospital, 2660 Oak Street, Vancouver, BC V6H 3Z6, Canada; Centre for Blood Research, University of British Columbia, 2350 Health Sciences Mall,
  • Mathews A; Michael Smith Laboratories, University of British Columbia, 2185 East Mall, Vancouver, BC V6T 1Z4, Canada; The Vancouver Prostate Centre, Vancouver General Hospital, 2660 Oak Street, Vancouver, BC V6H 3Z6, Canada; Centre for Blood Research, University of British Columbia, 2350 Health Sciences Mall,
  • Fenninger F; Michael Smith Laboratories, University of British Columbia, 2185 East Mall, Vancouver, BC V6T 1Z4, Canada; The Vancouver Prostate Centre, Vancouver General Hospital, 2660 Oak Street, Vancouver, BC V6H 3Z6, Canada; Centre for Blood Research, University of British Columbia, 2350 Health Sciences Mall,
  • Pfeifer CG; Michael Smith Laboratories, University of British Columbia, 2185 East Mall, Vancouver, BC V6T 1Z4, Canada; The Vancouver Prostate Centre, Vancouver General Hospital, 2660 Oak Street, Vancouver, BC V6H 3Z6, Canada; Centre for Blood Research, University of British Columbia, 2350 Health Sciences Mall,
  • Jefferies WA; Michael Smith Laboratories, University of British Columbia, 2185 East Mall, Vancouver, BC V6T 1Z4, Canada; The Vancouver Prostate Centre, Vancouver General Hospital, 2660 Oak Street, Vancouver, BC V6H 3Z6, Canada; Centre for Blood Research, University of British Columbia, 2350 Health Sciences Mall,
Stem Cell Reports ; 19(4): 456-468, 2024 Apr 09.
Article en En | MEDLINE | ID: mdl-38552634
ABSTRACT
The risk of iatrogenic disease is often underestimated as a concern in contemporary medical procedures, encompassing tissue and organ transplantation, stem cell therapies, blood transfusions, and the administration of blood-derived products. In this context, despite the prevailing belief that Alzheimer's disease (AD) manifests primarily in familial and sporadic forms, our investigation reveals an unexpected transplantable variant of AD in a preclinical context, potentially indicating iatrogenic transmission in AD patients. Through adoptive transplantation of donor bone marrow stem cells carrying a mutant human amyloid precursor protein (APP) transgene into either APP-deficient knockout or normal recipient animals, we observed rapid development of AD pathological hallmarks. These pathological features were significantly accelerated and emerged within 6-9 months post transplantation and included compromised blood-brain barrier integrity, heightened cerebral vascular neoangiogenesis, elevated brain-associated ß-amyloid levels, and cognitive impairment. Furthermore, our findings underscore the contribution of ß-amyloid burden originating outside of the central nervous system to AD pathogenesis within the brain. We conclude that stem cell transplantation from donors harboring a pathogenic mutant allele can effectively transfer central nervous system diseases to healthy recipients, mirroring the pathogenesis observed in the donor. Consequently, our observations advocate for genomic sequencing of donor specimens prior to tissue, organ, or stem cell transplantation therapies, as well as blood transfusions and blood-derived product administration, to mitigate the risk of iatrogenic diseases.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de Alzheimer Límite: Animals / Humans Idioma: En Revista: Stem Cell Reports Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de Alzheimer Límite: Animals / Humans Idioma: En Revista: Stem Cell Reports Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos