Alzheimer’s disease is a neurodegenerative disease showing alterations in neurotransmitters, above all in brain regions responsibles for cognition and emotions. In this disease, an imbalance between neurotransmitters, acetylcholine, GABA, glutamate, noradrenaline and serotonin are included. In brain examinations, serotonin levels and the specific receptors are found to be decreased.  In the hippocampus and prefrontal cortex, serotonin levels are associated with cognitive functions, whereas in the brainstem serotonin levels are related with symptoms of mood, for example depressed mood. Psychotic symptoms, i.e. paranoia or hallucinations which can occur in patients with Alzheimer’s disease are associated with dopamine and serotonin hyperactivity in brain regions responsibles for memory and emotions, i.e. the mesolimbic system and hippocampus.

Fig. 1. A. The interactions between neuronal cells containing the neurotransmitters acetylcholine, GABA, glutamate and serotonin in the brain region hippocampus and cortex in patients with Alzheimer’s disease. B. The interaction between the neuronal cells containing the neurotransmitters dopamine, GABA, glutamate, noradrenaline and serotonin in the brainstem and the hippocampus in depressed patients with Alzheimer’s disease.

The interaction between classical neurotransmitters and their specific receptors is shown in different brain areas. In clinical trials, the therapeutic effects of drugs interfering with specific receptors of serotonin have been examined to improve cognitive symptoms in Alzheimer’s disease. In these trials, drugs activating the serotonin receptor 5-HT₄ and drugs blocking the serotonin receptor 5-HT₆  showed a significant better effect in improving cognitive functions than placebo. The effect of such drugs on the formation of protein depositions is also examined. The appropriate use of antidepressant and antipsychotic drugs with an interaction with specific serotoninergic receptors is pointed out. Serotonin-selective antidepressant drugs significantly improve depressant symptoms and daily activities in Alzheimer patients and they are used to treat aggressive behaviour. Among the drugs to treat paranoia and hallucinations, drugs which do not raise blood pressure, glucose and cholersterol levels very much, should be preferred.

Felix-Martin Werner
Euro Akademie Pößneck, Germany

Publication

Serotonergic Drugs: Agonists/Antagonists at Specific Serotonergic Subreceptors for the Treatment of Cognitive, Depressant and Psychotic Symptoms in Alzheimer’s Disease.
Werner FM, Coveñas R.
Curr Pharm Des. 2016 Jan 26

Read offline:     

Related Articles:

	Role of dopamine in cortico-basal ganglia loop in psychosis Dopamine plays a major role in the formation of acute psychosis, as indicated by the dopamine hypothesis of schizophrenia. The relationship between acute psychosis and the dopamine system provides insight…
	Modulation of intracellular dopamine signaling by… Aripiprazole, a dopamine partial agonist, is one of the most widely prescribed atypical antipsychotics and its use in children and adolescents has become common. However, due to its favorable side…
	2-in-1: A new strategy against Parkinson´s Disease Parkinson´s disease is a neurological disorder, which affects around 6 mio people worldwide, a number being expected to double within the next 20 years. It is characterized by a progressive…
	Cryo-electron microscopy in drug development Cryo-electron microscopy (cryo-EM) is becoming the method of choice in structure determination of membrane proteins and has great potential for structure-based drug discovery (SBDD). Cryo-EM provides high-resolution structural information of…
	Orexin-A regulates dopamine D2 receptor in the mesolimbic… Orexin-A (orx-A) is a neuropeptide expressed exclusively in hypothalamic neurons. Orx-A acts through the activation of type-1 (Orx1R) and -2 (Orx2R) receptors present in the mesolimbic circuit and in other…
	Can tremor, depression and progression of the Parkinson’s… The short answer to this question is YES! Parkinson’s disease (PD) is the second most common age-related and progressive neurodegenerative disorder following Alzheimer’s disease (AD). It is associated with motor…