April 22, 2024

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New research challenges traditional understanding of Parkinson’s disease

New research challenges traditional understanding of Parkinson’s disease



New research challenges traditional understanding of Parkinson’s disease

Parkinson’s disease is the second most common progressive dementia after Alzheimer’s disease. Nearly 1 million people in the United States suffer from Parkinson’s disease, and globally, an estimated 10 million people have the disease. Nearly 90,000 new cases of Parkinson’s disease are diagnosed in the United States every year.

In a new study, Jeffrey Kordower, director of the ASU-Banner Neurodegenerative Disease Research Center at Arizona State University, and his colleagues have revealed crucial insights into the progression of Parkinson’s disease, bringing new hope to those struggling with this debilitating disease.

The research findings were published in the February 2024 issue of the journal Brain, titled “Nigrostriatal tau pathology in parkinsonism and Parkinson’s disease”.

This new research highlights the role of a key protein called tau in the early stages of this disease. Their findings suggest that aggregates of tau protein may initiate the neurodegeneration and cell death processes specific to this disease.

 

New research challenges traditional understanding of Parkinson's disease

 

 

These findings challenge the traditional view of Parkinson’s disease pathology, which typically considers alpha-synuclein as the hallmark diagnostic marker of the disease. This new research demonstrates how tau pathology actively contributes to the degeneration of neurons that produce dopamine in the brain, independent of alpha-synuclein. This discovery could shift the focus of Parkinson’s disease research, diagnosis, and treatment.

Kordower said, “Currently, a protein called alpha-synuclein is thought to play a major role in the pathogenesis of Parkinson’s disease. This new research emphasizes that misfolded tau may be a primary factor in causing the major motor symptoms of the disease.”

 

Shocking Progression

The progression of Parkinson’s disease is divided into different stages, with varying durations for different individuals. The typical stages of Parkinson’s disease listed by the Parkinson’s Foundation can help patients understand the changes that occur in this disease.

Parkinson’s disease affects individuals differently, with not everyone experiencing all symptoms, nor do they occur in the same order or intensity for everyone. Some individuals may experience these changes over 20 years or longer, while others may progress rapidly.

The progression of this disease is influenced by a combination of genetic and environmental factors. After diagnosis, many patients respond well to medications like levodopa, with this optimal treatment period lasting for several years. However, over time, adjustments to medications are often necessary, and symptoms may worsen.

In the past 25 years, the incidence of Parkinson’s disease has doubled, which may be attributed to population growth, aging, genetic susceptibility, lifestyle changes, and environmental pollution.

 

A Fresh Perspective

Tau protein accumulates in two regions: the substantia nigra and the putamen, both part of the basal ganglia in the brain. The substantia nigra is responsible for dopamine production, which is crucial for regulating movement, cognitive executive functions, and emotional edge activities.

As part of the striatum, the putamen is involved in the initiation, selection, and decision-making of movements, as well as learning, memory, language, and emotion. Dysfunction of the putamen can lead to various diseases, especially those related to motor function.

Parkinson’s disease manifests in various physical and psychological symptoms. These symptoms include rhythmic tremors, typically starting in limbs such as the hands or fingers; bradykinesia, leading to difficulty in completing simple tasks; muscle rigidity or stiffness; and difficulties with balance. In addition to these physical symptoms, Parkinson’s disease can also cause a range of mental and emotional changes, including depression and anxiety, sleep disturbances, memory difficulties, fatigue, and mood swings.

 

Traces in the Brain

The authors conducted their research using postmortem brain tissue from elderly individuals who had experienced varying degrees of motor impairments. Their study analyzed brain tissue from individuals without motor impairments, those with mild motor impairments but no Lewy body disease pathology in the substantia nigra, and brain tissue from patients clinically diagnosed with Parkinson’s disease.

 

New research challenges traditional understanding of Parkinson's disease

Image from Brain, 2024, doi:10.1093/brain/awad388

 

 

Lewy bodies are abnormal aggregates of alpha-synuclein in the brain and are a hallmark of several neurodegenerative diseases, including Parkinson’s disease and Lewy body dementia. In cases of Parkinson’s disease, Lewy bodies are primarily present in the substantia nigra of the brain, a region crucial for motor control, leading to characteristic motor symptoms such as stiffness, tremors, and bradykinesia.

This new study focused on a group of subjects with mild motor impairments, which were not severe enough to diagnose as Parkinson’s disease but still significant. The authors divided these subjects based on the presence or absence of alpha-synuclein and found tau pathology as a common factor.

The authors observed that brain tissue associated with mild motor impairments showed tau accumulation similar to that seen in advanced Parkinson’s disease patients, suggesting the involvement of tau in the early evolution of this disease. These findings open the door to early diagnosis and intervention, potentially slowing or altering the progression of this disease.

This new research also reveals the pathogenesis of Parkinsonism, which has symptoms similar to Parkinson’s disease but has a different underlying mechanism. This new research indicates that tau pathology in the substantia nigra putamen region of the brain is a common feature, providing a new perspective on the observation and treatment of various forms of Parkinsonism.

These research findings also highlight the potential of targeting tau pathology as a treatment approach for Parkinson’s disease. Since tau aggregation is associated with motor impairments and degeneration of the brain region responsible for dopamine production, interventions aimed at reducing tau aggregation may bring new hope for changing the trajectory of this disease.

New research challenges traditional understanding of Parkinson’s disease

References:

Yaping Chu et al. Nigrostriatal tau pathology in parkinsonism and Parkinson’s disease. Brain, 2024, doi:10.1093/brain/awad388.

New research challenges conventional picture of Parkinson’s disease https://medicalxpress.com/news/2024-02-conventional-picture-parkinson-disease.html

(source:internet, reference only)


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