LAUSR

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 13C‐isotope‐labeled brain extracts from mice expressing human amyloid‐β and track 13C‐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 13C‐lysine‐labeled amyloid‐β is not detectable in the brain whereas the mice incorporate 13C‐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.