Amyloid seeds formed by cellular uptake, concentration, and aggregation of the amyloid-beta peptide.

ABSTRACT: One of the neuropathological hallmarks of Alzheimer's disease (AD) is the amyloid plaque, primarily composed of aggregated amyloid-beta (Abeta) peptide. In vitro, Abeta(1-42), the major alloform of Abeta found in plaques, self-assembles into fibrils at micromolar concentrations and acidic pH. Such conditions do not exist in the extracellular fluid of the brain where the pH is neutral and Abeta concentrations are in the nanomolar range. Here, we show that extracellular soluble Abeta (sAbeta) at concentrations as low as 1 nM was taken up by murine cortical neurons and neuroblastoma (SHSY5Y) cells but not by human embryonic kidney (HEK293) cells. Following uptake, Abeta accumulated in Lysotracker-positive acidic vesicles (likely late endosomes or lysosomes) where effective concentrations (>2.

SUBMITTER: Hu X 

PROVIDER: S-EPMC2787156 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature