B09 Differential Sensitivity of Aggregate Markers in HDHQ140 Mouse Model

Background Huntington’s disease (HD), an inherited neurodegenerative disorder that is characterised histologically by the presence of intranuclear inclusions (NIIs) and the loss of neurons in the striatum and cortex. Protein aggregates are a hallmark of several neurodegenerative disorders including HD. These aggregates contain a variety of other proteins including ubiquitin. Aim The present study focused on producing a detailed characterisation of the neuronal pathology and designed to determine the sensitivity of three different antibodies in inclusion formations in knock-in HdhQ140 mice. Methods In order to fully assess the different protein deposition patterns in this mouse model, brains were taken at regular intervals and assessed using S830, MW8 or ubiquitin immunohistochemistry and stereology at between 4 and 21 months of age. Results In 4 months old HdhQ140, ubiquitin antibody showed more diffuse staining with minimum intranuclear inclusions in the olfactory tubercle, striatum, piriform cortex, and cortex. However, at the same age, the S830 antibody and MW8 showed more specific binding to intranuclear inclusions in the HdhQ140. As would be predicted the deposition of aggregated protein becomes more widespread at later ages. At 21 months of age the HdhQ140 mice showed increased S830, MW8 and ubiquitin immunoactivity. NIIs were visible with the all antibodies in the HdhQ140 mice at this stage. Conclusion The present study demonstrates the differential sensitivity of different antibodies in identifying NIIs in the HdhQ140 mouse line and that neuroanatomical markers of disease are present in young (4 month) HdhQ140 mice.