Dopamine System Dysfunction in Alzheimer's Disease

The dopaminergic system may be at the base of some neurobehavioral symptoms, as apathy and depression, and extrapyramidal symptoms, often seen in Alzheimer's disease patients. It can also have an impact on cognitive decline, as extrapyramidal symptoms, classically linked with dopamine dysfunction, are associated with increased risk of cognitive impairment and Alzheimer's disease progression. We review the knowledge of the dopaminergic system, emphasizing changes in Alzheimer's disease. Both animal models, post-mortem and in vivo human studies, point to a dopaminergic system dysfunction in this disease. Dopamine dysfunction seems more associated with neuronal loss, modification of dopamine receptors and anomalies in terminal function, including irregularities in dopamine metabolism, than with neurofibrillary tangles or β-amyloid plaques depositions. This dysfunction has an impact on both cognitive and non-cognitive symptoms. A better understanding of the dopaminergic system may help in understanding the pathophysiology of Alzheimer's disease and assist in the diagnosis. Clinical trials aimed at modulating the dopaminergic system may be promising in the treatment of symptoms associated with Alzheimer's disease.