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A direct interaction of Aβ with anionic cellular lipids mediates binding to neurons (Poster)


Dawkins, E and Vincent, AJ and Gasperini, R and Cui, H and Young, K and Foa, L and Small, DH, A direct interaction of Aβ with anionic cellular lipids mediates binding to neurons (Poster), 12th International Conference on Alzheimer's and Parkinson's Diseases, Florence, Italy (2013) [Conference Extract]

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Objectives: In Alzheimer's disease, an over-accumulation of Abeta in the brain causes amyloid plaque formation, neurodegeneration and cognitive decline. As neurodegeneration and cognitive decline may be mediated by a direct interaction of Abeta with neurons, we aimed to determine how Abeta binds to neurons, by investigating whether Abeta binds to lipids in the cell membrane. Methods: To assess Abeta cell binding and internalisation, live primary hippocampal cultures were treated with fluorescein-labelled Abeta1-42 (f-Abeta42), and imaged by live-cell microscopy. Cholera toxin subunit B and filipin labelling were performed on live cells prior to fixation in paraformaldehyde and imaging. Results: f-Abeta42 (10nM) was found to bind to the surface of neurons. Washout experiments demonstrated that most of the f- Abeta42 remained bound to the neuron surface and was not internalised after 4 hours. In contrast, microglia were found to rapidly internalise f-Abeta42 under the same conditions. To examine whether f-Abeta42 could bind to a lipid raft component of the cell membrane, the co-localisation of f-Abeta42 with cholera toxin subunit B was examined. Additionally, membrane cholesterol was labelled with filipin. There was minimal co-localisation of f-Abeta42 with cholera toxin subunit B or filipin. The in-vitro binding affinity of Abeta for all major classes of lipid was then examined using a protein-lipid overlay assay. In vitro, Abeta bound to anionic lipids such as phosphatidylserine and phosphatidic acid more than cholesterol or gangliosides. Conclusion: Abeta cell-binding may be mediated by a direct interaction with extracellular anionic lipids rather than specifically with ganglioside rich 'raft' domains.

Item Details

Item Type:Conference Extract
Research Division:Biomedical and Clinical Sciences
Research Group:Neurosciences
Research Field:Neurology and neuromuscular diseases
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Dawkins, E (Dr Edgar Dawkins)
UTAS Author:Vincent, AJ (Dr Adele Vincent)
UTAS Author:Gasperini, R (Dr Rob Gasperini)
UTAS Author:Cui, H (Mr Hao Cui)
UTAS Author:Young, K (Associate Professor Kaylene Young)
UTAS Author:Foa, L (Professor Lisa Foa)
UTAS Author:Small, DH (Professor David Small)
ID Code:93545
Year Published:2013
Deposited By:Menzies Institute for Medical Research
Deposited On:2014-08-07
Last Modified:2014-08-07

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