The International BNA 2025 Festival of Neuroscience

Ageing is the main risk factor for most neurodegenerative diseases.The most common form of neurodegenerative dementia in humans is Alzheimer's disease (AD), which is characterised by amyloid plaques, neurofibrillary tangles (NFT) containing hyperphosphorylated tau and increased neuroinflammation.Cognitive dysfunction syndrome (CDS) is an age-related condition found in domestic cats, with clinical features similar to those seen in human dementia.Additionally, aged cats and sheep develop neuropathology similar to changes observed in the brains of humans diagnosed with AD, such as amyloid-β (Aβ) accumulation and NFT.However, there is limited knowledge of the neurodegenerative processes in these species, and how closely their age-related neuropathology resembles that seen in humans.As glial cells such as microglia and astrocytes have been implicated in the pathogenesis of neurodegenerative diseases, we aimed to assess age-related changes to glial cell morphology and density in both cats and sheep and compare the results with glial cell changes in the brains of cats diagnosed with CDS.2.Transverse sections of brain regions were cut from formalin fixed, paraffin embedded blocks from cats and sheep of various ages, including cats diagnosed with CDS.Sections were labelled using antibodies for specific glial cell markers (Iba1 for microglia; GFAP for astrocytes) using standard immunohistochemical techniques.Images were taken from the grey matter, white matter, dentate gyrus and CA3 of labelled rostral and parietal sections from cat brains.ImageJ macros were used to determine cell size and density.Analysis of microglia process length and number was also performed.3.Using GraphPad Prism v9.2, one-way ANOVA was performed assuming a two-sided 95% confidence interval and equal variance to compare the effect of age and cognitive decline on glial cell morphology and density.Two-sample t-tests compared the differences in glial cells between cats with and without Aβ and tau pathology.Non-parametric tests were used to evaluate non-normal data.4.Microglia branch length decreased in the grey matter of the parietal and rostral cortex of brains from older cats diagnosed with CDS (16-19-years-old) compared to younger cats (2-6-years-old).Additionally, in some brain areas microglia branch length decreased and branch number increased in cats that were positive for intracellular hyperphosphorylated tau pathology.The study suggests that the glial cell morphological changes may be a response to neuropathology, which could be an age-related correlate of human AD.In sheep, we expect to see similar glial cell morphological changes with age and in response to age-related neuropathology.