Previous studies have claimed that the brains of AD patients were enriched with miR155 gene targets and that HHV-6A suppresses miR155. In this study, investigators sought to elucidate the association between miR155 and AD. The team knocked out miR155 in a transgenic strain of mice called APP/PSEN1, which has transgenes that increase deposition of amyloid-ß (AB) plaques. Readhead compared APP/PSEN1:miR155-/- to wild type (WT) miR155-/- and found that both groups showed increased deposition of AB plaques compared to controls. The WT miR155-/- group showed an increase in AB deposits and a decrease in learning capacity. The APP/PSEN1:miR155-/- group showed an increase in the frequency and size of the AB deposits compared to the rate of AB deposition usually expected in APP/PSEN1 mice and, surprisingly, an increase in learning capacity.
The researchers demonstrated that miR155 was upregulated in the dentate gyrus of APP/PSEN1 mice and the CA1 hippocampus of AD patients. This suggested that miR155 may act as a mediator of several important pathways in AD pathology, and that its gene targets may be upregulated or downregulated depending on the pathway. To test this, the researchers compared transcriptomic changes in WT miR155-/- mice and AD and found the same genes were upregulated downregulated in the cortices of both.
These novel findings indicate that miR155 may have a complex, multifaceted role in AD. Future research will likely aim to clarify the effects of miR155 and its manipulation in different pathways. Previous studies have suggested that HHV-6A suppresses miR155 (Caselli 2017, Rizzo 2017) and the downregulation of miR155 was found to accelerate AB plaque formation.
Read the full paper: Readhead 2020