De novo induction of amyloid-β deposition in vivo

Alzheimer's disease (AD), the most common type of senile dementia, is associated to the buildup of misfolded amyloid-beta (A beta) in the brain. Although compelling evidences indicate that the misfolding and oligomerization of A beta is the triggering event in AD, the mechanisms responsible for the initiation of A beta accumulation are unknown. In this study, we show that A beta deposition can be induced by injection of AD brain extracts into animals, which, without exposure to this material, will never develop these alterations. The accumulation of A beta deposits increased progressively with the time after inoculation, and the A beta lesions were observed in brain areas far from the injection site. Our results suggest that some of the typical brain abnormalities associated with AD can be induced by a prion-like mechanism of disease transmission through propagation of protein misfolding. These findings may have broad implications for understanding the molecular mechanisms responsible for the initiation of AD, and may contribute to the development of new strategies for disease prevention and intervention. Molecular Psychiatry (2012) 17, 1347-1353; doi: 10.1038/mp.2011.120; published online 4 October 2011