Possible role of neuromelanin in the pathogenesis of Parkinson's disease.

The numbers of nerve cells in the substantia nigra and locus caeruleus were counted, and the volume of their nucleolus and the amount of neuromelanin pigment they contain measured, in patients with Parkinson's disease and in age-matched and elderly individuals free from neurological illness. The number of pigmented nerve cells of both types is reduced by about 20% in the elderly when compared with age-matched controls. The melanin content of the remaining cells in the elderly is lessened (by 11% in substantia nigra and 21% in locus caeruleus) in such a way as to indicate that this age depletion in cell number results from a preferential loss of those nerve cells which contain the greatest amounts of melanin pigment. In Parkinson's disease there is a greater overall reduction in the amount of melanin within remaining cells (15% in substantia nigra, 25% in locus caeruleus) because of a more severe (80%) loss of the heavier pigmented cells. The basis for Parkinson's disease may therefore lie with an aggravation, possibly by secondary factors, of changes that occur within neurones of substantia nigra and locus caeruleus as part of their "normal" process of ageing.