Peripheral Induction of Alzheimer-Like Brain Pathology in Mice

Photo: Brain substance

Stained brain slice of a transgenic
mouse after intraperitoneal adminis-
tration of an extract containing mis-
folded Abeta. The stainings show the
induced pathological amyloid deposits;
© Science (AAAS)/Eisele

Alzheimer’s disease and a brain vascular disorder called cerebral beta-amyloid angiopathy are characterized by the accumulation of a protein fragment known as Abeta. In Alzheimer´s disease, misfolded Abeta is deposited mainly in so-called amyloid plaques, whereas in cerebral beta-amyloid angiopathy, the Abeta protein aggregates in the walls of blood vessels, interfering with their function and, in some cases, causing them to rupture with subsequent intracerebral bleeding.

In the study, Professor Mathias Jucker and first author Yvonne Eisele, together with their research team report that Abeta deposition can be induced in the transgenic mouse brain by the intraperitoneal administration of mouse brain extract containing misfolded Abeta. This induced Abeta deposition was primarily associated with the vasculature, but was also evident as amyloid plaques between nerve cells. The time needed to induce amyloid deposition in the brain was much longer for peripheral as compared to direct brain administration.

In both cases, the induced amyloid deposition also 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 Abeta 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“, points out Jucker. The present findings provide new clues on pathogenetic mechanisms underlying Alzheimer’s disease; further investigations will likely lead to new strategies for prevention and treatment.

MEDICA.de; Source: Hertie-Institut für klinische Hirnforschung (HIH)