Extracellular protein components of amyloid plaques and their roles in Alzheimer's disease pathology

Alzheimer's disease (AD) is pathologically defined by the presence of fibrillar amyloid beta (A beta) peptide in extracellular senile plaques and tau filaments in intracellular neurofibrillary tangles. Extensive research has focused on understanding the assembly mechanisms and neurotoxic effects of A beta during the last decades but still we only have a brief understanding of the disease associated biological processes. This review highlights the many other constituents that, beside A beta, are accumulated in the plaques, with the focus on extracellular proteins. All living organisms rely on a delicate network of protein functionality. Deposition of significant amounts of certain proteins in insoluble inclusions will unquestionably lead to disturbances in the network, which may contribute to AD and copathology. This paper provide a comprehensive overview of extracellular proteins that have been shown to interact with A beta and a discussion of their potential roles in AD pathology. Methods that can expand the knowledge about how the proteins are incorporated in plaques are described. Top-down methods to analyze post-mortem tissue and bottom-up approaches with the potential to provide molecular insights on the organization of plaque-like particles are compared. Finally, a network analysis of A beta-interacting partners with enriched functional and structural key words is presented.

Automated summary

Alzheimer's disease is pathologically defined by the presence of A beta in extracellular senile plaques and tau in intracellular neurofibrillary tangles. Besides A beta, other constituents are accumulated in the plaques, mainly focusing on extracellular proteins, which may contribute to disruptions in the protein network and lead to AD and copathology. This review provides an overview of extracellular proteins interacting with A beta and their potential roles in AD pathology, as well as methods to analyze the incorporation of proteins in plaques.