These are revealed by a study coordinated by Professor Marcello D'Amelio ofUniversità Campus Bio-Medico di Roma, just published in Nature Communications: it would be caused by the death of the neurons that form the ventral tegmental area, one of the main areas of the brain where dopamine is produced. The latter is an essential neurotransmitter for the proper functioning of the hippocampus, the brain structure on which memory depends.
Also discovered the link between the absence of dopamine and dysfunctions of the nucleus accumbens, a neuronal area involved in gratification and mood disorders. Depression, therefore, would not be a consequence of the pathology, but a potential signal of its onset
Photos of Professor D'Amelio and images of the study
Rome, April 3, 2017 – It is not in the hippocampus, the structure of the central nervous system primarily involved in memory functions, that the responsible for Alzheimer's disease must be sought: instead, the origin of the disease would be the death of the area of the brain that produces dopamine, a neurotransmitter essential for some important communication mechanisms between neurons. It is the surprising discovery made by a team of researchers coordinated by Professor Marcello D'Amelio, associate of Human Physiology and Neurophysiology at theUniversità Campus Bio-Medico di Roma.
I study, just published in the magazine Nature Communications. and in which other scientists from the laboratories of theUniversità Campus Bio-Medico di Roma, of the IRCCS Santa Lucia Foundation and the CNR of Rome, sheds new light on this serious pathology, which in Italy alone affects about half a million people over 60 years of age.
"We performed a thorough morphological analysis of the brain – explains D'Amelio – and we found out that when dopamine-producing neurons in the ventral tegmental area fail, the failure of this neurotransmitter causes the hippocampus to malfunction, even if all the cells of the latter remain intact".
No dopamine? No memory
Over the past 20 years, researchers have focused on the area on which the mechanisms of memory depend, believing that it was the progressive degeneration of hippocampal cells that caused Alzheimer's. Experimental analyses, however, have never recorded significant cell death processes inside it. No researcher had so far thought that other areas of the brain could be involved in the onset of the disease. "The ventral tegmental area – explains the teacher UCBM - had never been thorough in the study of Alzheimer's disease, because it is one deep part of the central nervous system, particularly difficult to investigate at a neuro-radiological level".
The protagonists of the research managed to clarify the molecular details underlying the lack of communication between nerve cells which, over time, leads to memory loss. Researchers have realized that – as in a domino effect – the death of the brain cells responsible for the production of dopamine causes the non-arrival of this substance in the hippocampus, causing its 'tilt' which generates memory loss. The study showed, already in the very early stages of the disease, the progressive death of only the neurons of the ventral tegmental area and not of those of the hippocampus. This mechanism turned out perfectly consistent with clinical descriptions of Alzheimer's pathology made by neurologists.
Confirmations from laboratory therapies
Further confirmation of the discovery was possible by administering two different therapies in the laboratory on animal models: one with L-DOPA, an amino acid dopamine precursor; the other based on a drug that inhibits its degradation. In both cases, after injecting the remedy the full memory recoveryrelatively quickly.
No dopamine? No good mood
During the tests, the scientists recorded – alongside the improvement of memory functions – also the full restoration of the motivational faculty and vitality. It's about a second, important, discovery. "We verified – clarifies D'Amelio – that the ventral tegmental area releases the dopamine also in the nucleus accumbens, the area that controls the gratification and mood disordersensuring its proper functioning. Thus, with the degeneration of dopamine-producing neurons, the risk of experiencing progressive loss of initiative also increases, an indication of a pathological alteration of mood".
These results confirm clinical observations that, from the earliest stages of Alzheimer's development, alongside episodes of memory loss patients report a decline in interest in life's activities, lack of appetite and the desire to take care of yourself, up to the trough.
Depression 'spy' of Alzheimer's, not vice versa
According to the research authors, changes in mood would not be - as was believed until now - a consequence of the appearance of Alzheimer's, but could rather represent a sort of 'alarm bell' behind which the subtle beginning of the pathology is hidden. "Memory loss and depression D'Amelio points out. they are two sides of the same coin".
Alzheimer's and Parkinson's: common goal for treatment
The perspectives that this study discloses are manifold. “The next step – explains the teacher who coordinated all the experimentation – it will have to be there development of more effective neuro-radiological techniques, capable of giving us access to the secrets kept in the ventral tegmental area, to discover its functioning and degeneration mechanisms. Furthermore, the results obtained suggest that do not underestimate the depressive phenomena in the diagnosis of Alzheimer's, because they may go hand in hand with memory loss. Finally, since Parkinson's too is caused by the death of dopamine-producing neurons, it is possible to imagine that the future therapeutic strategies for both diseases will be able to focus on a common goal: 'selectively' prevent the death of these neurons".
The experimental data also clarified why so-called 'dopamine degradation inhibitors' drugs – whose therapeutic validity has been much discussed over time – prove to be useful only for some patients: they only function in the early stages of the disease, when a good number of ventral tegmental area neurons still survive. With the death of all the cells in this area, dopamine stops being produced altogether and the drug is obviously no longer effective. “The other substance administered in the laboratory during the trial, called L-DOPA – specifies the doctor Annalisa Nobili, first signature of the studio – cannot be given to patients except in the last stages of the disease because, as also emerged in the cases of Parkinson's, causes phenomena of particular toxicity which can aggravate their conditions".
Although the validation of an effective cure for Alzheimer's is still far away, the search results conducted by Professor D'Amelio and the other scientific partners they add a decisive piece in understanding the mechanisms from which this dreaded disease starts. Hopefully shortening the time that separates Science from the day when it will finally be possible to stop it.
