Monoamine neurons in aging and Alzheimer's disease

The integrity of dopaminergic, noradrenergic and serotonergic neurons in normal aging and Alzheimer's disease is reviewed. Loss of dopaminergic innervation of the neostriatum is a prominent age-related change, which corresponds with the age-related loss of dopaminergic cell bodies from the substantia nigra. This change is regionally specific, since dopaminergic innervation of the neocortex and the neostriatum are not affected. Although there is an age-related loss of noradrenergic cell bodies from the locus coeruleus, most studies indicate normal concentrations of noradrenaline in target areas. There is also evidence for reduced serotonergic innervation of the neocortex and, less convincingly, the neostriatum. Alzheimer's disease is associated with more pronounced noradrenergic and serotonergic denervation but, unlike normal aging, dopaminergic innervation of neostriatum is intact; although dopamine neurons are probably dysfunctional in this region. Studies relating neuronal markers to the symptomatology of Alzheimer's disease indicate that dysfunction of monoamine neurons is more closely linked to non-cognitive than to cognitive changes in behavior. In addition, monoaminergic therapies have been successful in ameliorating affective and psychotic behaviors along with sleep disturbances in both Alzheimer's disease and senescence. It seems likely that monoaminergic therapies (developed as we learn more about alterations in dopamine, noradrenaline and serotonin) will continue to be necessary to treat such behavioral disturbances.