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Research article - Peer-reviewed, 2018

Protofibrillar and Fibrillar Amyloid-beta Binding Proteins in Cerebrospinal Fluid

Rahman, M. Mahafuzur; Westermark, Gunilla T.; Zetterberg, Henrik; Hard, Torleif; Sandgren, Mats


Aggregation and deposition of misfolded amyloid-beta (A beta) peptide in the brain is central to Alzheimer's disease (AD). Oligomeric, protofibrillar, and fibrillar forms of A beta are believed to be neurotoxic and cause neurodegeneration in AD, but the toxicity mechanisms are not well understood and may involve A beta-interacting molecular partners. In a previous study, we identified potential A beta(42) protofibrillar-binding proteins in serum and cerebrospinal fluid (CSF) using an engineered version of A beta(42) (A beta 42CC) that forms protofibrils, but not fibrils. Here we studied binding of proteins to A beta(42) fibrils in AD and non-AD CSF and compared these with protofibrillar A beta 42CC-binding partners. A beta(42) fibrils sequestered 2.4-fold more proteins than A beta 42CC protofibrils. Proteins with selective binding to fibrillar aggregates with low nanomolar affinity were identified. We also found that protofibrillar and fibrillar A beta-binding proteins represent distinct functional categories. A beta 42CC protofibrils triggered interactions with proteins involved in catalytic activities, like transferases and oxidoreductases, while A beta(42) fibrils were more likely involved in binding to proteoglycans, growth factors and neuron-associated proteins, e.g., neurexin-1, -2, and -3. Interestingly, 10 brain-enriched proteins were identified among the fibril-binding proteins, while protofibril-extracted proteins had more general expression patterns. Both types of A beta aggregates bound several extracellular proteins. Additionally, we list a set of CSF proteins that might have potential to discriminate between AD and non-AD CSF samples. The results may be of relevance both for biomarker studies and for studies of A beta-related toxicity mechanisms.


Alzheimer's disease; amyloid-beta; biomolecular interaction; cerebrospinal fluid; fibrils; protofibrils

Published in

Journal of Alzheimer's Disease
2018, volume: 66, number: 3, pages: 1053-1064
Publisher: IOS PRESS

Authors' information

Rahman, Mahafuzur
Swedish University of Agricultural Sciences, Department of Molecular Sciences
Westermark, Gunilla T.
Uppsala University
Zetterberg, Henrik
University of Gothenburg
Swedish University of Agricultural Sciences, Department of Molecular Sciences
Swedish University of Agricultural Sciences, Department of Molecular Sciences

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