Alexander Disease
https://www.eneuro.org/content/eneuro/early/2025/03/05/ENEURO.0504-24.2025.full.pdf
Alexander Disease (AxD) is neuropathologically characterised by Rosenthal fibres (GFAP protein accumulation in astrocytes) and clinically evaluated with motor and cognitive deficits. However, how these hallmarks are linked to each other remains unclear. In the present study, researchers developed a novel rat model of AxD, called R237H, to investigate neuronal dysfunctions and behavioural deficits in the context of such an astrocytic pathology. Cerebral gene expression analysis revealed alterations already at an early stage of the disease when Rosenthal fibres were present, but motor symptoms were yet absent. These changes were accompanied by neurodegeneration as assessed by impaired transmission of information between neurons (cerebral plasticity) and a decrease in the number of synapses, the principal components of cerebral plasticity. Additional memory tests confirmed the onset of cognitive deficits in the R237H rat model, reminiscing the clinical features of AxD. These observations show that the R237H rat model recapitulates key pathological and cognitive features of AxD and suggest this animal model as a valuable tool for investigating AxD disease mechanisms and potential therapeutic approaches.