Death of neuronal clusters contributes to variance of age at onset in Huntington's disease

Huntington's disease (HD) is a fatal neurodegenerative disease caused by an expanded polyglutamine (polyQ) repeat in the protein huntingtin. Due to selective neuronal loss in the cortex and striatum, HD patients develop various movement disturbances, psychological changes, and dementia. Symptoms usually appear in individuals between 30 and 50 years of age. The principal cause of variability of age at onset (AO) is the length of the polyQ repeat. Several additional genetic factors contributing to the variance have been identified. At least 35% of the variance, however, remains unexplained. Using a stochastic model, we show that the pattern of cell death of striatal neurons might contribute up to 20% of variance of AO.