Change search
ReferencesLink to record
Permanent link

Direct link
Binding of Human Proteins to Amyloid-beta Protofibrils
Swedish University of Agricultural Sciences (SLU), Sweden .ORCID iD: 0000-0001-9238-7246
2015 (English)In: ACS Chemical Biology, ISSN 1554-8929, E-ISSN 1554-8937, Vol. 10, no 3, 766-774 p.Article in journal (Refereed) Published
Abstract [en]

The progressive neurodegeneration in Alzheimers disease is believed to be linked to the presence of prefibrillar aggregates of the amyloid-beta (A beta) peptide in the brain. The exact role of these aggregates in the disease pathology is, however, still an open question. Any mechanism by which oligomeric A beta may cause damage to neuronal cells must, in one way or another, involve interactions with other molecules. Here, we identify proteins in human serum and cerebrospinal fluid that bind to stable protofibrils formed by an engineered variant of A beta 42 (A beta(42CC)). We find that the protofibrils attract a substantial number of protein binding partners. Many of the 101 identified proteins are involved in lipid transport and metabolism, the complement system, or in hemostasis. Binding of representative proteins from all of these groups with micromolar affinity was confirmed using surface plasmon resonance. In addition, binding of apolipoprotein E to the protofibrils with nanomolar affinity was demonstrated. We also find that aggregation of A beta enhances protein binding, as lower amounts of proteins bind monomeric A beta. Proteins that bind to A beta protofibrils might contribute to biological effects in which these aggregates are involved. Our results therefore suggest that an improved understanding of the mechanisms by which A beta causes cytotoxicity and neurodegeneration might be gained from studies carried out in biologically relevant matrices in which A beta-binding proteins are present.

Place, publisher, year, edition, pages
2015. Vol. 10, no 3, 766-774 p.
National Category
Biochemistry and Molecular Biology
URN: urn:nbn:se:kth:diva-165223DOI: 10.1021/cb5008663ISI: 000351558700015PubMedID: 25469473ScopusID: 2-s2.0-84925355903OAI: diva2:810171

QC 20150506

Available from: 2015-05-06 Created: 2015-04-24 Last updated: 2015-05-06Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMedScopus

Search in DiVA

By author/editor
Lendel, Christofer
In the same journal
ACS Chemical Biology
Biochemistry and Molecular Biology

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 15 hits
ReferencesLink to record
Permanent link

Direct link