Ageing and neurotoxins as causative factors in idiopathic parkinson's disease—a critical analysis of the neurochemical evidence

Abstract

1. Idiopathic Parkinson's disease (PD) is set apart from other Parkinsonian conditions by a specific interregional (caudate-putamen) as well as a subregional (rostralcaudal) pattern of striatal dopamine (DA) loss. 2. Using the characteristic patterns of striatal DA loss as neurochemical criteria, a critical evaluation of the “ageing/neurotoxin” hypothesis of idiopathic PD is presented. 3. Although both ageing of the brain DA neurones and MPTP (as an example of a DA-specific neurotoxin) reproduce some aspects of the subregional striatal DA loss found in idiopathic PD, neither of these two mechanisms mimicks the large caudate-putamen difference in DA loss (with the putamen much more affected than the caudate nucleus) which is typical of idiopathic PD. 4. From the discussed observations the conclusion is drawn that the pathoetiological factor, or factors, operative in idiopathic PD must involve a mechanism preferentially damaging the nigral DA neurones which project to the putamen.