Isotope-labeled amyloid-ß does not transmit to the brain in a prion-like manner after peripheral administration.
EMBO Rep
; 23(7): e54405, 2022 07 05.
Article
en En
| MEDLINE
| ID: mdl-35620875
Findings of early cerebral amyloid-ß deposition in mice after peripheral injection of amyloid-ß-containing brain extracts, and in humans following cadaveric human growth hormone treatment raised concerns that amyloid-ß aggregates and possibly Alzheimer's disease may be transmissible between individuals. Yet, proof that Aß actually reaches the brain from the peripheral injection site is lacking. Here, we use a proteomic approach combining stable isotope labeling of mammals and targeted mass spectrometry. Specifically, we generate 13 C-isotope-labeled brain extracts from mice expressing human amyloid-ß and track 13 C-lysine-labeled amyloid-ß after intraperitoneal administration into young amyloid precursor protein-transgenic mice. We detect injected amyloid-ß in the liver and lymphoid tissues for up to 100 days. In contrast, injected 13 C-lysine-labeled amyloid-ß is not detectable in the brain whereas the mice incorporate 13 C-lysine from the donor brain extracts into endogenous amyloid-ß. Using a highly sensitive and specific proteomic approach, we demonstrate that amyloid-ß does not reach the brain from the periphery. Our study argues against potential transmissibility of Alzheimer's disease while opening new avenues to uncover mechanisms of pathophysiological protein deposition.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Priones
/
Enfermedad de Alzheimer
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
EMBO Rep
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2022
Tipo del documento:
Article
País de afiliación:
Noruega
Pais de publicación:
Reino Unido