A study ofUniversità Campus Bio-Medico di Roma, together with the Santa Lucia IRCCS Foundation of Rome and conducted on experimental models, confirmed that dopaminergic stimulation is effective in reducing the hyperexcitability of the hippocampus, a condition underlying the onset of epilepsy and that it can contribute to the progressive cognitive damage in the disease Alzheimer's. 

Rome, 18 January 2024 - Alzheimer's disease is the leading cause of dementia in the Italian population and over 600.000 people live with this condition. Although the diagnosis of the disease is, to date, exclusively linked to the symptoms reported to the neurologist by the patient and measured by the neuropsychologist, research is proposing more and more solutions for the early diagnosis of Alzheimer's.

A promising area is in the study of the areas of the brain responsible for the production of dopamine, an important neurotransmitter whose deficit is usually linked to Parkinson's disease for which numerous therapies already exist today. 

In this context, the research team of prof. Marcello D'Amelio, Head of the Molecular Neuroscience laboratory of the Santa Lucia IRCCS and Full Professor of Human Physiology of the Campus Bio-Medico University, for some years has focused on the Ventral Tegmental Area (VTA), an area of ​​the brain linked to the production of dopamine and involved in numerous brain functions, as a passage point for numerous brain circuits that connect different areas of the brain.  

A new study by Prof.'s team. D'Amelio confirmed that dopamine levels in the hippocampus, the area of ​​the brain where memory is located, play a role in the long pre-clinical phase of Alzheimer's disease, characterized by cortical hyperexcitability, small epileptic episodes (often asymptomatic and detectable with electroencephalographic insights).

“Acting before the patient even shows obvious symptoms of the disease is very complex,” explains the professor. D'Amelio: “To achieve this it is necessary to identify with reasonable certainty the patient who will actually develop the disease and intervene as soon as possible to preserve the neurons. In fact, not all patients with the typical lesions of Alzheimer's develop the disease and our previous clinical study on the VTA made it possible to identify very early the patients who will develop Alzheimer's disease by isolating them from whom, despite having amyloid lesions , is less at risk. 

With this study we add a further piece to the knowledge of the pre-clinical phases of Alzheimer's. By intervening on the dopaminergic mechanisms of the brain with drugs well known for their effectiveness in Parkinson's disease, we have managed, in experimental models and not yet in humans, to preserve neuronal activity in areas affected by the disease by reducing hippocampal hyperexcitability which can lead to epileptic activities, typical of the initial stages of Alzheimer's disease, and contribute to the worsening of cognitive decline". 

The mechanism triggered by the lack of dopamine, in turn linked to an early degeneration of the Ventral Tegmental Area, prevents correct activation of interneurons which have the function of controlling cortical excitability.

This study confirms the importance of dopaminergic circuits in Alzheimer's disease, historically linked to the deficiency of other neurotransmitters including acetylcholine. This is a promising area of ​​research because it would allow the therapies currently available for Parkinson's disease to be transferred to Alzheimer's disease. 

Concludes the prof. D'Amelio: “The early and accurate diagnosis of Alzheimer's disease is essential for selecting patients who must follow specific therapeutic paths, including pharmacological ones, including therapies with monoclonal antibodies against beta-amyloid.

It is, in fact, evident that the earlier the start of treatment, the greater the chances of slowing down or hopefully stopping the cognitive deterioration that leads the patient to the complete loss of autonomy.

This work goes in the direction of identifying specific alterations of cortical excitability as disease biomarkers which, together with others currently available, can better characterize the stage of disease development and help the clinician to undertake the most suitable therapeutic path."