Increased Aβ Production Leads to Intracellular Accumulation of Aβ in Flotillin-1-Positive EndosomesRajendran L. · Knobloch M. · Geiger K.D. · Dienel S. · Nitsch R. · Simons K. · Konietzko U.
aMax Planck Institute of Molecular Cell Biology and Genetics, and bNeuropathology, Uniklinikum, Techincal University of Dresden, Dresden, Germany; cPsychiatry Research, University of Zurich, Zurich, Switzerland
Extracellular accumulation of Aβ in β-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 Aβ accumulates inside the cells and mice develop behavioral deficits well before visible extracellular β-amyloid accumulation. Here we show that intracellular Aβ accumulates in flotillin-1 positive endocytic vesicles. We also demonstrate that flotillin-1 is not only associated with intracellular Aβ in transgenic mice but also with extracellular β-amyloid plaques in AD patient brain sections.
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