DECREASED CEREBROSPINAL-FLUID NITRATE LEVELS IN PARKINSONS-DISEASE, ALZHEIMERS-DISEASE AND MULTIPLE SYSTEM ATROPHY PATIENTS

Nitric oxide (NO) is a recently discovered endogenous mediator of vaso dilatation, neurotransmission, and macrophage cytotoxicity. NO is thou ght to have a function in memory and in long-term potentiation. At hig h concentrations NO is neurotoxic and may play a role in neurodegenera tion. NO is formed from L-arginine by the enzyme NO synthase (NOS), fo r which tetrahydrobiopterin (BH4) is a necessary co-factor. Alzheimer' s disease (AD) and, to a lesser degree, Parkinson's disease (PD) are t hought to be associated with increased microglial activity, suggesting that NO production may be increased. Alternatively, in circumstances of reduced levels of intracellular L-arginine or BH4, NO production is diminished and neurotoxic oxygen radicals may be produced. Since BH4 is decreased in AD and PD brains, these diseases may be associated wit h decreased NO production. We investigated these two alternatives by m easuring the NO degradation products nitrite and nitrate in cerebrospi nal fluid (CSF) of PD (n = 103), AD (n = 13), and multiple system atro phy (MSA; n = 14) patients and controls (n = 20). We found for all pat ient groups, compared with controls, significantly decreased levels of nitrate, but not nitrite. This finding seems to indicate a decreased NO production of the central nervous system (CNS) in these neurodegene rative disorders.