Neurochemical Studies of Alzheimer's Disease

Neurochemical studies of post-mortem human brain have made a major contribution to understanding the neuronal basis of neurodegenerative disease and formed the basis of rational therapies for such disorders. The application of this approach to the neurochemical pathology of Alzheimer's disease was pioneered by David Bowen. By combining assessment of post-mortem tissue (where the disease has usually run its full course) with tissue obtained ante-mortem (where the disease course is incomplete), it has been possible to (1) establish which neurones are lost in the disease, (2) determine which neurones are lost early in the course of the disease, and (3) discern which changes relate with the symptomatology of the disease. Thus, loss of cholinergic, noradrenergic and serotonergic innervation to the cortex occurs at an early stage, since markers of the neurones are lost in both post-mortem and ante-mortem tissue. By contrast, dopaminergic innervation remains intact and markers of cortical GABAergic interneurones are affected in post-mortem tissue only, suggesting that loss of GABAergic neurones occurs only at a late stage of the disease. Cholinergic markers and the number of pyramidal cell perikarya correlate with the severity of dementia, suggesting that loss of cholinergic and EAA neurones is the major contributor to the cognitive impairments of Alzheimer's disease. Loss of noradrenergic and serotonergic neurones probably contributes to the emergence of non-cognitive impairments in behaviour. Possible causes of selective neuronal loss are discussed.