cyclohydrolase have found both to be spared in AD suggesting that the lesion must be at the level of phosphate eliminating enzyme. BH4 synthesis in human temporal and frontal lobes declines with age, but sepiapterin reductase remains constant, and is possibly through a reduced ability to

55. The effects of phenylalanine and tyrosine on implications in Alzheimer's disease

U. Dhanesha, C.G. Hamon, J.A. Blair, R.J. Leem- ing and G.F.A. Harding (Birmingham, UK)

Early studies of Alzheimer's disease (SDAT) using a sample of 91 patients have established that the visual evoked cortical potential (VECP) to flash stimulation can be used as a diagnostic indicator of the condition (Wright et al., Docum. Ophthalmol. 1986, 62:89). It was found that the P2 component of the flash VECP was delayed whereas the P100 component to pattern reversal stimulation was of normal latency. This com- bination of results from the two visual stimuli was recognised to be more specific than either the electroencephalogram or computerised tomography in the diagnosis of SDAT. Biochemically, SDAT is also associated with decreased tetrahydrobiopterin synthesis (THB). This agent is a rate controlling fac- tor in the synthesis of the neurotransmitters noradrenaline and dopamine (Leeming and Blair,

convert dihydroneopterintriphosphatc to tetrahydrobiopterin due to reduced phosphate eliminating enzyme capacity. We suggest that AD may be a superimposed form of this process such that the deficiency in tetrahydrobiopterin causes a deficit in the catecholaminergic neurotransmitters.

the visual evoked cortical potential and the

Clin. Chim Acta 1980, 108: 103). A recent study on 10 patients showed a high correlation between the delayed latency of the flash P2 and decreased biop- terin levels in urine (0.83 p0.01) (Wright et al., in press). These results indicated that the flash P2 com- ponent is affected by cortical activity mediated by the dopamine and noradrenaline neurotransmitter systems. The present study using phenylalanine and tyrosine has demonstrated that these agents shorten the la- tency of the flash P2 component and P100 component of the pattern response in normal subjects. These agents are involved in the biosynthesis of dopamine and noradrenaline. The results confirm the hypothesis that the flash P2 component is affected by the noradrenergic system. It is proposed that the effect is modulatory and stems from the locus coeruleus.

56. Reaction of the rat brain after intracerebroventricular administration of young, elderly and senile dementia of Alzheimer type (SDAT) brain homogenates

Ph. van den Bosch de Aguilar, F. De Paermentier, M. Grosjean, P. Heuschling and B. Knoops (Louvain, Belgium)

The presence of a possible specific pathogenic factor inducing SDAT is still under debate. To test this possibility we have administered 30 ul of temporal cortex homogenates from autopsied patients (young, elderly and SDAT) into the right ventricle of 3-month old rats. Human brain homogenates induce glial and neuronal necrosis in the host brain two weeks after the injection. The necrotic cells are characterized by an extensive vacuolation of the cytoplasm and rem- nants of cell organelles are scattered between the vacuoles. The number of necrotic cells has been determined in the cortex and the hippocampus on the

contralateral side to the injection site. When rats of the Louvain Wistar strain were used, the results clearly demonstrate that cellular necrosis is related to the age of the human injected material and the in- volvement of dementia. Moreover, necrosis is more evident in the hippocampus than in the cortex. The same experiment performed in other rat strains (non- Louvain Wistar or Sprague-Dawley) resulted in less abundant necrosis with no statistical differences be- tween treatments. These results show that a rat strain (genetically predisposed ?) is more susceptible to a necrotic factor present in the human material. An exaggerated cytotoxic activity during aging could lead to SDAT. This rat strain could provide a new animal model for the study of the pathogenesis of SDAT.

57. Degeneration of the serotonergic system

P. Herregodts, P. Cras, M. Bruyland, Y. Michotte, J.J. Martin and G. Ebinger (Brussels and Antwerp, Belgium)

Locoregional concentrations of serotonin (5-hydrox- ytryptamine), the catecholamines norepinephrine, epinephrine and dopamine, and their major metabolites (5-hydroxyindoleacetic acid, 3-methoxi-

in Alzheimer's disease

4-hydroxyethylene glycol, 3,4-dihydroxyphenylace- tic acid and homovanillic acid) were measured in 17 regions of the left hemisphere of two brothers and one sister suffering from Alzheimer's disease with very early onset. Clinical diagnosis was confirmed by neuropathologi- cal examination of the right hemisphere and the brainstem. Neuronal losses and neurofibrillary

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