The presence of Aβ seeds, and not age per se, is critical to the initiation of Aβ deposition in the brain

The deposition of the beta-amyloid (A beta) peptide in senile plaques and cerebral A beta-amyloid angiopathy can be seeded in beta-amyloid precursor protein (APP)-transgenic mice by the intracerebral infusion of brain extracts containing aggregated A beta. Previous studies of seeded beta-amyloid induction have used relatively short incubation periods to dissociate seeded beta-amyloid induction from endogenous beta-amyloid deposition of the host, thus precluding the analysis of the impact of age and extended incubation periods on the instigation and spread of A beta lesions in brain. In the present study using R1.40 APP-transgenic mice (which do not develop endogenous A beta deposition up to 15 months of age) we show that: (1) seeding at 9 months of age does not induce more A beta deposition than seeding at 3 months of age, provided that the incubation period (6 months) is the same; and (2) very long-term (12 months) incubation after a focal application of the seed results in the emergence of A beta deposits throughout the forebrain. These findings indicate that the presence of A beta seeds, and not the age of the host per se, is critical to the initiation of A beta aggregation in the brain, and that A beta deposition, actuated in one brain area, eventually spreads throughout the brain.