Beta amyloid aggregates induce sensitised TLR4 signalling causing long-term potentiation deficit and rat neuronal cell death
More about Open Access at the CrickAuthors list
Craig Hughes Minee Choi Jee-Hyun Yi Seung-Chan Kim Anna Drews Peter St George-Hyslop Clare Bryant Sonia Gandhi Kwangwook Cho David KlenermanAbstract
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.
Full text links
Publisher website (DOI) 10.1038/s42003-020-0792-9
Figshare View on figshare
Europe PubMed Central 32071389
Pubmed 32071389
Keywords
Related topics
Type of publication