Mechanism of amyloid plaque formation suggests an intracellular basis of Aβ pathogenicity

• DOI: 10.1073/pnas.0904532106
• Publication Date: 2010-01-20T04:53:28Z
• Authors: Ralf P. Friedrich; Katharina Tepper; Raik Rönicke; Malle Soom; Martin Westermann; Klaus Reymann; Christoph Kaether; Marcus Fändrich
• Keywords: Amyloid (mycology); P3 peptide; Cell membrane

The formation of extracellular amyloid plaques is a common patho-biochemical event underlying several debilitating human conditions, including Alzheimer’s disease (AD). Considerable evidence implies that AD damage arises primarily from small oligomeric forms Aβ peptide, but the precise mechanism pathogenicity remains to be established. Using cell culture system reproducibly leads plaques, we show here single plaque represents template-dependent process critically involves presence endocytosis- or phagocytosis-competent cells. Internalized peptide becomes sorted multivesicular bodies where fibrils grow out, thus penetrating vesicular membrane. Upon formation, cells undergo death and intracellular structures become released into space. These data imply pathogenic activity attributed, at least in part, aggregates.