AD cognition sciences and technologies of the National Research Council (Cnr-Istc).
The three scholars – Daniele Caligiore, Flora Giocondo and Massimo Silvetti – have reassembled the results of various researches on Alzheimer’s and Parkinson’s conducted in various fields, from genetics to neurophysiology, like a puzzle. Thus they came to trace the two diseases back to the same neurodegenerative phenomenon which they called NES (Neurodegenerative Elderly Syndrome) and which would be characterized by three progressive stages.
The first ‘seeding phase’, Caligiore observes, “begins many years before the onset of clinical symptoms and in it there may be a progressive loss of neurons that produce norepinephrine and serotonin. We propose that this initial damage may be mainly caused by malfunctioning of a very widespread protein in our body, alpha-synuclein. The initial dysfunctions can be due to various genetic, environmental or lifestyle factors, called ‘seeds’, and can affect different parts of the body. In particular, the malfunctioning alpha-synuclein can have different access routes to the brain: it could originate in situ or be transported from the intestine”. The type of seed or trigger and the part of the brain and body affected by the initial alpha-synuclein dysfunctions, the route of entry and the type of neuromodulator most involved in this embryonic stage of the disease influence the possible future progression of NES towards transformation into Parkinson’s or Alzheimer’s.
In the second phase “dysfunctions of the neurons which synthesize the neuromodulator dopamine and which are located in two different regions of the brain begin to manifest: in the ventral tegmental area (management of cognitive and motivational aspects) and in the substantia nigra pars compacta (management of motor aspects )”, adds Giocondo. “The clinical symptoms are still silent, thanks to compensatory mechanisms that maintain the balance of the different concentrations of neuromodulators”: therefore this phase of the NES is called ‘compensation’. The third and final phase is that of bifurcation in which “NES becomes Alzheimer’s if the dopaminergic area most affected is the ventral tegmental area, or becomes Parkinson’s if the area most affected is the substantia nigra pars compacta”, continues Silvetti.
If confirmed by future empirical studies, the NES hypothesis could revolutionize research on these two neurodegenerative diseases, indicating new ways for early diagnosis and for the development of therapies to be implemented in the very early stage, before the manifestation of clinical symptoms.
“Also artificial intelligence could be a tool to verify or refute the NES hypothesis. In this regard – says Caligiore – at the Cnr-Istc we are developing machine learning algorithms to combine and analyze large quantities of heterogeneous data (clinical, genetic , magnetic resonance imaging) on Alzheimer’s and Parkinson’s made available from international databases in order to find common neurodegeneration trajectories between the two diseases”.
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