The genetics of disorders with synuclein pathology and parkinsonism

Despite being considered the archetypal non-genetic neurological disorder, genetic analysis of Parkinson's disease has shown that there are at least t hree genetic loci. Furthermore, these analyses have suggested that the phen otype of the pathogenic loci is wider than simple Parkinson's disease and m ay include Lewy body dementia and some forms of essential tremor. Identific ation of alpha-synuclein as the first of the loci involved in Parkinson's d isease and the identification of this protein in pathological deposits in o ther disorders has led to the suggestion that it may share pathogenic mecha nisms with multiple system atrophy, Alzheimer's disease and prion disease a nd that these mechanisms are related to st synuclein pathway to cell death. Finally, genetic analysis of the synuclein diseases and the tau diseases m ay indicate that this synuclein pathway is an alternative to the tau pathwa y to cell death.