Although there are several hypotheses about what causes Parkinson's disease, its etiology is unknown, making it impossible to develop a treatment that stops the progression of Parkinson's. Now a study published in the prestigious journal Brain. In the Journal of Neurology, researchers from the Neurodegenerative Diseases Research Group at the Vall d’Hebron Research Institute (VHIR) have shed light on how the disease begins and the role of the adaptive immune system in neuronal death.
The aim of this study was to characterize the infiltration of T lymphocytes, both CD4 and CD8, into the substantia nigra in order to shed light on their potential role in the loss of dopaminergic neurons in this region of the brain which is mainly affected in Parkinson's disease. The results obtained in the study suggest that the cytotoxic attack of CD8 T lymphocytes precedes the aggregation of α-synuclein, and that they produce the neuronal death of dopaminergic neurons, both in the initial presymptomatic phase of the disease and in the chronification of this. "We started the postmortem brain study of cases with Parkinson's disease and saw that the density of CD8 T lymphocytes in the brain parenchyma correlated with the level of neuronal death. We then analyzed lymphocyte infiltration in cases of patients with incidental Lewy bodies, which are considered early stages of the disease”, explains Dr. Jordi Bové, principal investigator of the Neurodegenerative Diseases Research Group at the Vall d’Hebron Research Institute (VHIR).
Cases with incidental Lewy bodies (iLBD) were separated into two groups: one that included cases with Lewy bodies in the substantia nigra, among other regions, and another that basically had them only in the olfactory bulb. "This is an innovative approach because iLBD cases are usually treated as a single group, but precisely this allowed us to discover that infiltration and neural contacts not only preceded neuronal death, but also happened before we could observe any kind of aggregate”, he says. “It is precisely in this very initial phase where we see the greatest infiltration of CD8 T lymphocytes and which also have a greater cytotoxic potential. Therefore, all indications are that the source of the disease is due to this infiltration. Now, the next step is to understand why they are infiltrating”, concludes Dr. Bové.
This study may become a first step in definitively determining the cause of Parkinson’s disease and in establishing new therapeutic targets to stop or even prevent the disease. At the same time, given that this study also shows that neuronal death occurs concomitantly with the accumulation and aggregation of α-synuclein, it will be necessary to study the relationship between this protein and the immune response, to understand the etiopathogenic mechanisms of Parkinson's disease and probably all synucleinopathies. This research has been funded by the following institutions: Carlos III Health Institute (Ministry of Science and Innovation), the Department of Health of the Generalitat de Catalunya (Strategic Plan for Health Research and Innovation) and the Tatiana Pérez de Guzmán el Bueno Foundation.
About Parkinson's disease
Parkinson’s disease is the second most common form of neurodegenerative disease and its most obvious motor symptoms are stiffness, tremor at rest, and slowness of movement. These symptoms can be explained, in part, by the loss of dopaminergic neurons, which contain the pigment neuromelanin, located in the so-called black matter, although other regions of the brain are also affected.
Another feature of this disease is the presence of Lewy bodies and neurites in the brains of patients, which are aggregates that contain, among other components, the protein α-synuclein. The presence of Lewy bodies in different regions of the brain has described different stages of the disease, with the olfactory bulb being one of the first regions of the brain to be affected. In this sense, a significant proportion of Parkinson's patients have a loss of sense of smell before motor disorders become apparent.
Other non-motor symptoms, such as REM sleep disturbances, make up the premotor phase of the disease and can manifest years before the substantia nigra is affected and the disease is diagnosed. The existence of postmortem brain tissue in individuals who have not had motor symptoms in life but who contain Lewy bodies in different regions, allows us to study the premotor phase of the disease.