Quantitative Comparison of Dense-Core Amyloid Plaque Accumulation in Amyloid-? Protein Precursor Transgenic Mice.

ABSTRACT: There exist several dozen lines of transgenic mice that express human amyloid-? protein precursor (A?PP) with Alzheimer's disease (AD)-linked mutations. A?PP transgenic mouse lines differ in the types and amounts of A? that they generate and in their spatiotemporal patterns of expression of A? assemblies, providing a toolkit to study A? amyloidosis and the influence of A? aggregation on brain function. More complete quantitative descriptions of the types of A? assemblies present in transgenic mice and in humans during disease progression should add to our understanding of how A? toxicity in mice relates to the pathogenesis of AD. Here, we provide a direct quantitative comparison of amyloid plaque burdens and plaque sizes in four lines of A?PP transgenic mice. We measured the fraction of cortex and hippocampus occupied by dense-core plaques, visualized by staining with Thioflavin S, in mice from young adulthood through advanced age. We found that the plaque burdens among the transgenic lines varied by an order of magnitude: at 15 months of age, the oldest age studied, the median cortical plaque burden in 5XFAD mice was already ?4.5 times that of 21-month-old Tg2576 mice and ?15 times that of 21-24-month-old rTg9191 mice. Plaque-size distributions changed across the lifespan in a line- and region-dependent manner. We also compared the dense-core plaque burdens in the mice to those measured in a set of pathologically-confirmed AD cases from the Nun Study. Cortical plaque burdens in Tg2576, APPSwePS1?E9, and 5XFAD mice eventually far exceeded those measured in the human cohort.

SUBMITTER: Liu P 

PROVIDER: S-EPMC5272806 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature