Parkinson, identified a risk factor for the development of dementia

When we talk about Parkinson’s disease, we immediately think of its most common symptoms, namely tremor, muscle stiffness and movement disorders. But often those affected by this pathology – the second most common degenerative disease (after Alzheimer’s) and the fastest growing among all neurological diseases (6 million people affected worldwide, of which about 400,000 in Italy alone) – also suffers from early memory defects, which sometimes disappear, sometimes worsen remaining limited to memory function, and in other cases degenerate to the point of developing dementia. Understanding when these cognitive disorders, almost always mild at first, can be considered real ‘predictors’ of dementia is therefore essential to favor an early diagnosis and intervene in a timely manner with adequate therapeutic strategies.

A study on an animal model conducted by the Institute of Biochemistry and Cell Biology of the National Research Council (Cnr-Ibbc), by the Irccs San Raffaele, by the Telethon Institute of Genetics and Medicine (Tigem) and by the Catholic University was made with just that in mind. “We wondered – explains Elvira De Leonibus, researcher at Cnr-Ibbc and Tigem, who coordinated the study published in Nature Parkinson’s disease NPJ – if the onset of memory deficits and their course could depend on the area of the brain in which alpha-synuclein accumulates, a molecule normally present in the brain, which when aggregated can lead to the death of neurons, in particular those that produce dopamine, the neurotransmitter involved in motricity, emotional and cognitive processes , and which decreases dramatically in Parkinson’s disease. In other words, she was interested in whether the site in the brain where these proteins accumulate could be considered a possible regulator or risk factor for dementia.”

I study

The hypothesis tested by the researchers, in fact, starts from the fact that the brain area in which alpha-synucleinopathy originates, the disease associated with the worsening of memory deficits, may regulate the progression of dementia from the first memory disturbances. neurological disorders and abnormal accumulation of alpha-synuclein in the nervous system. “The region of the brain in which this disease develops is important, because the aggregated synuclein proteins are then transported to the terminations of the neurons, and then to the synapses – continues the researcher – Therefore, the more a region of the brain is connected to the others through so many terminations, the more the accumulations of proteins will be able to compromise more brain areas and develop dementia more easily, causing the loss of functions in every behavioral area”.
In fact, the different areas of the brain perform generally distinct functions. “The hippocampus, for example, is important for the formation of long-term memory, while the midbrain, which is the area where the neurons that die in Parkinson’s disease are present, regulates all motor and motivational functions, thanks to the release of dopamine – underlines De Leonibus – Using a mouse model, in which it is possible to increase the expression of the protein at the origin of cognitive symptoms in specific areas of the brain, we observed that when alpha-synucleinopathy takes place in the midbrain motor disturbances appear first, then memory deficits, which tend to worsen and be accompanied by other behavioral disturbances in a general picture very similar to that of dementia. On the other hand, when the pathology originates in the hippocampus, alpha-synuclein produces memory defects earlier than it does in the midbrain, but these are cognitive symptoms that remain stable for months, do not worsen over time and are not associated with neurodegeneration . It can therefore happen that in subjects, even young ones, mild cognitive defects never turn into dementia, while in others, in which they appear later, they worsen until they lead to the loss of all cognitive functions”.

Because results matter

Research shows that pathological alpha-synuclein in different brain areas can therefore give rise to different behavioral defects, with a different progression, depending on how closely the brain region is connected to the others. And that more connected areas, such as the midbrain, could make it easier for the disease to be transmitted to other areas of the brain. “Having indicators capable of telling us this – concludes the expert – is essential not only to intervene in a timely manner, but also to experiment with therapies that in the next ten years will probably be able to slow down the course of dementia”.