Pyramidal Neurone Modulation: A Therapeutic Target for Alzheimer's Disease

Abstract

It is proposed that pyramidal neurones are central to the pathogenesis and cognitive dysfunction of AD on the basis that they are the site of tangle formation and the mismetabolism of APP and degenerate, and that such cells are the focus of neurotransmitter abnormalities. Anatomical studies in animal and human brain are revealing which neurotransmitter receptors are present on populations of pyramidal neurones and a microdialysis approach has demonstrated the ability of such receptors to alter neuronal activity. Specifically, it is proposed that cholinomi-metics used for the symptomatic treatment of AD may work by influencing the activity of pyramidal neurones and that this action may be potentiated by a 5-HT_1Aantagonist. The contribution of pyramidal neurone transmission failure to the spread of pathology in AD is the subject of continuing investigation.