Protein deposits linked to Alzheimer's disease can be triggered by peripheral administration outside the brain.
A team of researchers from the Hertie Institute of Clinical Brain Research (HIH, University Hospital Tübingen, University of Tübingen) and the German Center for Neurodegenerative Diseases (DZNE) has show that pathological “protein deposits linked to Alzheimer's disease and cerebral amyloid angiopathy can be triggered not only by the administration of pathogenic misfolded protein fragments directly into the brain but also by peripheral administration outside the brain.”
Publishing their results in Science, the researchers have added to previous reports that injecting dilute extracts from Alzheimer’s disease brain tissue or from Aβ-laden mouse brain tissue into trangeneic mice brains stimulates aggregation of Aβ in the mouse brain. With intraperitoneal administration of mouse brain extract that contained misfolded Aβ, they saw induction of Aβ deposition that was most related with the vasculature, but was also seen as amyloid plaques between nerve cells. Induction of amyloid deposition took much longer with peripheral than direct brain administration, but with both, amyloid deposition triggered “several neurodegenerative and neuroinflammatory changes commonly observed in the brains of patients with Alzheimer´s disease and cerebral beta-amyloid angiopathy.”
"The finding that mechanisms exist allowing for the transport of Aβ aggregates from the periphery to the brain raises the question of whether protein aggregation and propagation, which may also be involved in other neurodegenerative brain diseases, can be induced by agents originating in the periphery," said co-author, professor MathiasJucker. “The present findings provide new clues on pathogenetic mechanisms underlying Alzheimer's disease; further investigation will likely lead to new strategies for prevention and treatment.”
The molecular principle of inducing protein aggregation is similar to that of prion diseases. Prion disease can also be initiation by introducing prions at sites that are peripheal to the brain, something the current study found isn’t a unique characteristic of prion diseases, which had been assumed. However, despite this finding, as well as the suggested mechanistic similarities between prion diseases and Alzheimer’s disease, no evidence exists to show that Alzheimer’s disease or cerebral amyloid angiopathy are transmitted in the same way as prion diseases between beings.
How do these findings impact your practice and your patients who either have Alzheimer’s disease or are at risk for developing Alzheimer’s disease? Do theyimpact your practice? Will you hold out hope that the findings could lead to future agents for preventing or treating cerebrovascular diseases? Tell us what you think? Post a comment below, and let’s a get a dialog started!