Isotope-labeled amyloid-β does not transmit to the brain in a prion-like manner after peripheral administration

EMBO Rep. 2022 Jul 5;23(7):e54405. doi: 10.15252/embr.202154405. Epub 2022 May 27.


Findings of early cerebral amyloid-β deposition in mice after peripheral injection of amyloid-β-containing brain extracts, and in humans following cadaveric human growth hormone treatment raised concerns that amyloid-β aggregates and possibly Alzheimer's disease may be transmissible between individuals. Yet, proof that Aβ 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-β and track 13 C-lysine-labeled amyloid-β after intraperitoneal administration into young amyloid precursor protein-transgenic mice. We detect injected amyloid-β in the liver and lymphoid tissues for up to 100 days. In contrast, injected 13 C-lysine-labeled amyloid-β is not detectable in the brain whereas the mice incorporate 13 C-lysine from the donor brain extracts into endogenous amyloid-β. Using a highly sensitive and specific proteomic approach, we demonstrate that amyloid-β 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.

Keywords: Alzheimer’s disease; brain; multiple reaction monitoring immuno-mass spectrometry; prion-like; seeding.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease* / metabolism
  • Amyloid beta-Peptides / metabolism
  • Amyloid beta-Protein Precursor / genetics
  • Amyloid beta-Protein Precursor / metabolism
  • Animals
  • Brain / metabolism
  • Disease Models, Animal
  • Humans
  • Isotopes
  • Lysine
  • Mammals / metabolism
  • Mice
  • Mice, Transgenic
  • Prions* / metabolism
  • Proteomics


  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • Isotopes
  • Prions
  • Lysine