Home Medizin Studie liefert entscheidende Erkenntnisse über den Verlauf der Parkinson-Krankheit

Studie liefert entscheidende Erkenntnisse über den Verlauf der Parkinson-Krankheit

von NFI Redaktion

The Parkinson’s disease, the second most common form of progressive dementia after Alzheimer’s disease, affects nearly one million people in the United States and an estimated ten million people worldwide. Nearly 90,000 new cases of Parkinson’s disease are diagnosed in the U.S. every year.

In a new study, Jeffrey Kordower, Director of ASU-Banner Neurodegenerative Disease Research Center, and his colleagues reveal crucial insights into the progression of Parkinson’s disease, offering new hope for patients struggling with this debilitating condition.

The research highlights the role of a critical protein called Tau in the early stages of the disease. The findings suggest that Tau protein aggregates may trigger processes of neuronal damage and features of the disease’s neuronal death.

The results challenge the conventional view of Parkinson’s disease pathology, which typically focuses on the protein Alpha-Synuclein as a classic diagnostic hallmark of the disease. The new study shows how Tau pathology could be actively involved in the degeneration of dopamine-producing neurons in the brain independently of Alpha-Synuclein. This discovery could shift the focus of Parkinson’s research, diagnosis, and treatment.

Currently, it is believed that a protein called Alpha-Synuclein is the main player in the pathogenesis of Parkinson’s disease. This study highlights that misfolded Tau might be the first factor causing the major motor symptoms of the disease.“


Jeffrey Kordower, Professor, School of Life Sciences at ASU

The study appears in the current issue of the journal Brain.

Shocking Progress

The progression of Parkinson’s disease occurs in different stages, and the timeline can vary significantly from person to person. The typical stages of Parkinson’s disease, as described by the Parkinson’s Foundation, can help patients understand the changes they experience.

The disease affects people in different ways, and not everyone will experience all symptoms or in the same order or intensity. For some, the changes may occur over a period of 20 years or longer; for others, the disease progresses rapidly.

The course of the disease is influenced by a combination of genetic and environmental factors. After diagnosis, many people respond well to medication such as Levodopa, and this optimal timeframe can last for many years. However, over time, medication adjustments are often necessary, and symptoms may worsen.

The prevalence of Parkinson’s has doubled in the past 25 years, possibly due to population growth, aging, genetic predisposition, lifestyle changes, and environmental pollution.

A New Perspective

The Tau protein accumulates in two regions: the Substantia nigra and the Putamen, both parts of the Basal ganglia in the brain. The Substantia nigra is responsible for dopamine production, which is essential for modulating movement, cognitive executive functions, and emotional limbic activity.

The Putamen, a component of the dorsal striatum, is involved in movement initiation, selection, and decision-making, as well as learning, memory, language, and emotions. Dysfunction of the Putamen can lead to various disorders, especially those related to motor function.

A variety of physical and psychological symptoms characterize Parkinson’s disease. These include rhythmic tremors, often starting in limbs such as the hand or fingers; slowness of movement, which can lead to difficulties in performing simple tasks; muscle stiffness or rigidity; and balance difficulties.

In addition to these physical symptoms, Parkinson’s disease can also cause various mental and emotional changes, including depression and anxiety, sleep disturbances, memory issues, fatigue, and emotional changes.

Traces of Disease in the Brain

The scientists conducted the study using postmortem brain tissue from older adults with varying degrees of motor impairments. The research analyzed brain tissue from individuals without motor deficits, with mild motor deficits with and without Lewy pathology in the nigral region of the brain, and from individuals clinically diagnosed with Parkinson’s disease.

Lewy bodies are abnormal aggregates of the protein Alpha-Synuclein that accumulate in the brain, and they are a hallmark of several neurodegenerative diseases, including Parkinson’s and Lewy body dementia.

In Parkinson’s, Lewy bodies are mainly found in the Substantia nigra, a region of the brain crucial for motor control, leading to characteristic motor symptoms like rigidity, tremors, and Bradykinesia (slow movement).

The study focused on a cohort of subjects with mild motor impairments, not severe enough to diagnose Parkinson’s but still significant. When categorizing these subjects based on the presence or absence of α-Synuclein, the researchers found that Tau pathology was a common denominator.

The researchers observed that brain tissue associated with minimal motor deficit showed similar Tau accumulations to those in advanced Parkinson’s disease, suggesting that Tau’s role plays early in the disease’s development. These findings open doors for earlier diagnosis and intervention, potentially slowing or altering the disease’s progression.

The research also sheds light on Parkinsonism, a condition that mimics the symptoms of Parkinson’s disease but differs in underlying mechanisms. The study suggests that Tau pathology in the nigrostriatal region of the brain is a common feature, offering a new perspective on examining and treating different forms of Parkinsonism.

The results also highlight the potential of targeted treatment of Tau pathology as a therapeutic approach for Parkinson’s disease. As Tau aggregation correlates with motor deficits and degeneration of dopamine-producing regions of the brain, interventions to reduce Tau accumulation could offer new hope for changing the course of the disease.

Joining Kordower are researchers from the Neurodegenerative Diseases Research Unit, Biogen, Cambridge, Massachusetts; Alignment of Science on Parkinson’s Disease (ASAP) Collaborative Research Network, Chevy Chase, Maryland; Neurology, School of Medicine, Georgetown University Medical Center, Washington, DC; Department of Neurology, University of Alabama in Birmingham; and Pacific Parkinson’s Research Center and Djavad Mowafaghian Center for Brain Health, University of British Columbia, Vancouver.

Source:

Journal Reference:

Chu, Y.et al. (2023). Nigrostriatal Tau Pathology in Parkinsonism and Parkinson’s Disease. Brain. doi.org/10.1093/brain/awad388.

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