Imaging Amyloid‐β Membrane Interactions: Ion‐Channel Pores and Lipid‐Bilayer Permeability in Alzheimer's Disease

The accumulation of the amyloid‐β peptides (Aβ) is central to the development of Alzheimer's disease. The mechanism by which Aβ triggers a cascade of events that leads to dementia is a topic of intense investigation. Aβ self‐associates into a series of complex assemblies with different structur...

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Bibliographic Details
Published in:Angewandte Chemie 2023-06, Vol.135 (25), p.e202215785-n/a
Main Author: Viles, John H.
Format: Article
Language:English
Subjects:
Alzheimer's disease
Amyloid
Annular Oligomers
Assemblies
Aufsatz
Aufsätze
Channel pores
Chemistry
Cytotoxicity
Dementia disorders
Electron Microscopy
Homeostasis
Lipid membranes
Lipids
Membrane permeability
Membranes
Neurodegenerative diseases
Peptides
Permeability
Pore formation
Protofibrils
Structure
Toxicity
β-Amyloid
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Summary:The accumulation of the amyloid‐β peptides (Aβ) is central to the development of Alzheimer's disease. The mechanism by which Aβ triggers a cascade of events that leads to dementia is a topic of intense investigation. Aβ self‐associates into a series of complex assemblies with different structural and biophysical properties. It is the interaction of these oligomeric, protofibril and fibrillar assemblies with lipid membranes, or with membrane receptors, that results in membrane permeability and loss of cellular homeostasis, a key event in Alzheimer's disease pathology. Aβ can have an array of impacts on lipid membranes, reports have included: a carpeting effect; a detergent effect; and Aβ ion‐channel pore formation. Recent advances imaging these interactions are providing a clearer picture of Aβ induced membrane disruption. Understanding the relationship between different Aβ structures and membrane permeability will inform therapeutics targeting Aβ cytotoxicity. Self‐association of Amyloid‐β (Aβ) into oligomeric, protofibril, annular and fibril assemblies is intimately linked with neuronal toxicity and Alzheimer's disease. Aβ can have a range of impacts on the lipid membrane including a carpeting effect and ion‐channel pore formation. Imaging these interactions with the lipid bilayer is providing a clearer picture of Aβ‐induced membrane permeability, which leads to loss of cellular homeostasis.
ISSN:0044-8249
1521-3757
DOI:10.1002/ange.202215785