Increased Abeta production leads to intracellular accumulation of Abeta in flotillin-1-positive endosomes.

Extracellular accumulation of Abeta in beta-amyloid plaques is thought to be associated with the neurodegeneration observed in Alzheimer's disease (AD) patients, although a lack of correlation with cognitive decline raised doubts on this hypothesis. In different transgenic mouse models Abeta accumulates inside the cells and mice develop behavioral deficits well before visible extracellular beta-amyloid accumulation. Here we show that intracellular Abeta accumulates in flotillin-1 positive endocytic vesicles. We also demonstrate that flotillin-1 is not only associated with intracellular Abeta in transgenic mice but also with extracellular beta-amyloid plaques in AD patient brain sections.