Mouse, Huntington’s Disease

Huntington’s disease (HD) is a progressive neurodegenerative genetic disorder, caused by an autosomal dominant mutation on the Huntingtin gene (HTT). The mutation of HTT means that the length of a repeated section of the gene exceeds a normal range, resulting in an abnormal long poly-glutamine repeat on one part of the protein, causing the proteins to create hydrogen bonds and to form protein aggregates. The presence of the mutant proteins results in gradual damage to specific areas of the brain but the exact way this happens is not fully understood. The pathologic changes in the brain of HD patients affect muscle coordination and leads to cognitive decline, dementia and psychiatric problems. HD is also the most common genetic cause of chorea which is abnormal involuntary writhing movements.
Research into the mechanism of HD is primarily focused on the brain pathology the disease produces. Modeling the disease in animal models is critical for understanding the fundamental mechanisms of the disease and for supporting the early stages of drug development. The size and amount of the aggregates combined with the large area of the ROIs (Cerebral Cortex, Striatum, and Hippocampus) has previously made quantification very difficult.
By using digital image analysis based on virtual slides to quantify the presence of protein aggregates for evaluating e.g. effect of a drug in HD treatment studies, it is possible to obtain high-throughput quantification of aggregates without compromising the accuracy and quality of the results.