[Pharmaceutical research strategies in Alzheimer's disease].
The hypothesis that the symptomatology of Alzheimer's disease is attributable to loss of cortical cholinergic innervation is supported by post-mortem studies demonstrating both reduced choline acetyltransferase (CAT) activity and reduced high-affinity choline uptake (HAChT) in the cortex, and neuron cell loss in the basal forebrain nucleus basalis of Meynert. Cholinergic denervation occurs early in the course of the disease and correlates with the severity of cognitive impairment. Pharmaceutical research strategies based on the cholinergic hypothesis and focusing on the development of acetylcholine esterase inhibitors and muscarinic agonist will be discussed. An alternative hypothesis to explain the dementia of Alzheimer's disease is the glutamatergic hypothesis. This is based on postmortem evidence indicating loss of glutamate, reduced binding and uptake of the neuro-transmitter and loss of pyramidal cells in the cortex. The possibility of developing glutamatergic drugs for treating the symptomatology of Alzheimer's disease will be considered. Studies have also indicated that the cellular processes involved in Alzheimer's disease occur in non-neuronal cells as well as in the brain. The possibility that Alzheimer's disease is a systemic disease and that drugs can be developed to treat the disease process will be considered.
Wülfert
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Centre de Recherches UCB-Pharma, Braine-l'Alleud, Belgique.
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans
Stratégies de recherches pharmaceutiques dans la maladie d'Alzheimer.