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

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

Automated summary

Using stable isotope labeling and targeted mass spectrometry, the study shows that amyloid-beta does not reach the brain from the periphery, contradicting the theory of transmissibility in Alzheimer's disease.