Neurosurgery and Neuroscience

Alzheimer's disease is a neurodegenerative disease with cognitive, depressive and psychotic symptoms. We summarize the neurotransmitter alterations above all in the hippocampus and frontal/temporal cortices. In these brain areas, hypoactivity of acetylcholine and hyperactivity of noradrenaline at the beginning of the disease and hypoactivity of noradrenaline can be found. Glutamate exerts an excitotoxic effect and the presynaptic inhibitory neurotransmitter GABA shows hypoactivity. In depressive symptoms, a deficiency of monamines occurs in the brainstem and hippocampus. In psychotic symptoms, hyperactivity of dopamine and serotonin can be detected in the hippocampus and the ventral tegmental area. Neural networks in the corresponding brain areas are suggested. In Alzheimer's disease, 5-HT4 and 5-HT7 agonists and 5-HT3 and 5-HT6 antagonists have been suggested for the treatment of cognitive symptoms. In pioneer clinical studies, 5-HT4 agonists and 5-HT6 antagonists have shown a therapeutic effect, which was higher than placebo. In depressive symptoms, 5-HT reuptake inhibitors have a good therapeutic effect and can be used to treat aggressive behavior. In psychotic symptoms, 5-HT2A antagonists and second generation antipsychotic drugs can be administered, although the adverse effects should be considered. Because in Alzheimer's disease, a neurotransmitter imbalance between GABAA GABAergic neurons with hypoactivity and NMDA glutamatergic neurons with hyperactivity can be found, the first clinical studies with combined GABAA agonists and NMDA antagonists will be described.