Work

Beta amyloid aggregates induce sensitised TLR4 signalling causing long-term potentiation deficit and rat neuronal cell death

Year: 2020

Type: article

Abstract: The molecular events causing memory loss and neuronal cell death in Alzheimer's disease (AD) over time are still unknown. Here we found that picomolar concentrations of soluble oligomers of synthetic beta amyloid (Aβ42) aggregates incubated with BV2 cells or rat astrocytes caused a sensitised response of Toll-like receptor 4 (TLR4) with time, leading to increased production of TNF-α. Aβ aggregates caused long term potentiation (LTP) deficit in hippocampal slices and predominantly neuronal cell death in co-cultures of astrocytes and neurons, which was blocked by TLR4 antagonists. Soluble Aβ aggregates cause LTP deficit and neuronal death via an autocrine/paracrine mechanism due to TLR4 signalling. These findings suggest that the TLR4-mediated inflammatory response may be a key pathophysiological process in AD.

Source: Communications Biology

DOI: 10.1038/s42003-020-0792-9

Authors: Craig Hughes, Minee L. Choi, Jee-Hyun Yi, Seung-Chan Kim, Anna Drews, Peter St. George-Hyslop, Clare Bryant, Sonia Gandhi, Kwangwook Cho, David Klenerman

Institutions: University of Cambridge, The Francis Crick Institute, UCL Queen Square Institute of Neurology, University College London, University of Bristol, Institute for Basic Science, King's College London, UK Dementia Research Institute, German Center for Neurodegenerative Diseases

Language: English

Topic: Alzheimer's disease research and treatments

Subfield: Cellular and Molecular Neuroscience

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,290

Funders: Wellcome Trust, National Institute for Health and Care Research, Royal Society, University College London, Alzheimer’s Research UK, UK Dementia Research Institute, Medical Research Council, H2020 European Research Council

Awards: The role of alpha-synuclein misfolding in Parkinson's disease., G4114659138, Inflammasome formation in infectious and inflammatory diseases., Characterising protein oligomers and their role in neurodegenerative disease in humans, Dissecting molecular mechanisms of Parkinson's disease, Mechanisms of neurotoxicity of amyloid aggregates

OpenAlex ID: W3002969891

FWCI: 5.126

Cites: 29

Cited by: 114

Related to: 10