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Biomacromolecules. 2019 Nov 11;20(11):4208-4217. doi: 10.1021/acs.biomac.9b01116. Epub 2019 Oct 22.

Differential Roles of Plasma Protein Corona on Immune Cell Association and Cytokine Secretion of Oligomeric and Fibrillar Beta-Amyloid.

Author information

1
ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash Institute of Pharmaceutical Sciences , Monash University , 381 Royal Parade , Parkville , Victoria 3052 , Australia.
2
Materials Research and Education Center , Auburn University , Auburn , Alabama 36849 , United States.
3
Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity , University of Melbourne , Melbourne , Victoria 3052 , Australia.
4
ARC Centre for Excellence in Convergent Bio-Nano Science and Technology , University of Melbourne , Melbourne , Victoria 3052 , Australia.
5
Infection and Immunity Program & Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute , Monash University , Clayton , Victoria 3800 , Australia.
6
Australian Institute for Bioengineering and Nanotechnology , The University of Queensland , Brisbane , Queensland 4072 , Australia.
7
Melbourne Sexual Health Clinic and Infectious Diseases Department, Alfred Hospital , Monash University Central Clinical School , Carlton , Victoria 3053 , Australia.

Abstract

Alzheimer's disease (AD) is a primary neurological disease with no effective cure. A hallmark of AD is the presence of intracellular tangles and extracellular plaques derived from the aberrant aggregation of tau- and beta-amyloid (Aβ). Aβ presents in the brain as well as in cerebrospinal fluid and the circulation, and Aβ toxicity has been attributed to amyloidosis and inflammation, among other causes. In this study, the effects of the plasma protein corona have been investigated with regard to the blood cell association and cytokine secretion of oligomeric (Aβo) and fibrillar Aβ1-42(Aβf), two major forms of the peptide aggregates. Aβo displayed little change in membrane association in whole blood or washed blood (i.e., cells in the absence of plasma proteins) at 37 °C, while Aβf showed a clear preference for binding with all cell types sans plasma proteins. Immune cells exposed to Aβo, but not to Aβf, resulted in significant expression of cytokines IL-6 and TNF measured in real-time by a localized surface plasmon resonance sensor. These observations indicate greater immune cell association and cytokine stimulation of Aβo than Aβf and shed new light on the contrasting toxicities of Aβo and Aβf resulting from their differential capacities in acquiring a plasma protein corona. These results further implicate a close connection between Aβ amyloidosis and immunopathology in AD.

PMID:
31600059
DOI:
10.1021/acs.biomac.9b01116

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