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New study surveys genetic changes linked with Parkinson’s disease

After Alzheimer’s, Parkinson’s disease (PD) is the leading neurodegenerative disorder, affecting close to a million Americans, with 50,000 new cases diagnosed every year. A progressive disorder of the nervous system affecting movement, PD typically strikes adults in mid-life. In many cases, the spread of the disease to other brain areas leads to Parkinson’s disease dementia, characterized by deterioration of memory, reason, attention and planning.

In new research, Travis Dunckley, PhD., a researcher at Arizona State University’s Biodesign Institute, examines genetic modifications associated with the development of PD and PD-associated dementia, bringing new investigative tools to bear.

The research, which appears in the current issue of the journal Neurology Genetics, uses RNA sequencing to illuminate two phenomena linked with the onset of Parkinson’s disease, differential gene expression and alternative splicing of genes.

The study tracks specific gene alterations implicated in the development of Parkinson’s, noting that gene expression and alternative splicing offer complementary information critical to a full understanding of disease progression. The findings deepen the scientific understanding of the disease, while suggesting new avenues for more comprehensive diagnosis.

“This work shows that the degeneration of key functional brain areas in Parkinson’s disease is more genetically complex than previously appreciated,” Dunckley says. “Very small changes in the way in which genes are processed, not just large changes in which genes are turned on or off, can contribute to Parkinson’s disease.”

Dr. Dunckley is a researcher in the newly formed Neurodegenerative Disease Research Center, a unique partnership between Arizona State University (ASU), and Banner Health. The research alliance focuses on advancing the scientific study, treatment and prevention of Alzheimer’s, Parkinson’s and other neurodegenerative diseases.

By marrying Phoenix-based Banner Health, one of the nation’s largest nonprofit health systems, with the formidable resources of Arizona State University (ASU), one of the nation’s largest public research universities, the NDRC aspires to become a national focal point for research into neurodegenerative diseases, which affect millions of people every year and take an increasing financial toll on an overburdened healthcare system.

The national economic burden of PD alone amounts to tens of billions of dollars yearly, a figure expected to grow substantially as the population ages.

Persistent menace

Parkinson’s disease affects roughly 1 percent of those over 50 years old, with the incidence markedly increasing with age. Presently, there is no cure for the disease, though medication and surgery may be used to help manage some of the symptoms.

Neurons located in a region of the brain known as the substantia nigra are the primary target for Parkinson’s disease. Some of these neurons produce dopamine, which decreases as the illness advances, causing deterioration of normal movement.

Neuroinflammation, oxidative stress, mitochondrial dysfunction and aberrant alternative splicing have all been implicated in the trajectory of Parkinson’s disease, though precise causes of the illness-involving the deterioration of dopaminergic neurons in the mid-brain accompanied by high rates of dementia-remain murky.

The main symptoms of PD are tremor of the hands, arms, legs, jaw and face; bradykinesia (or slowness of movement); stiffness and rigidity of the limbs and trunk and impaired balance and coordination. Cell losses in other brain regions, including the brain stem and olfactory bulb, have also been implicated in Parkinson’s.

The primary neurological hallmark of the disease is the formation of so-called Lewy bodies-microscopic aggregates of a protein known as ?-synuclein. Lewy bodies are involved in other neurological disorders as well, including dementia with Lewy bodies (DLB). Evidence suggests that dementia with Lewy bodies, Parkinson’s disease and Parkinson’s disease dementia may all be related to abnormalities in brain processing of ?-synuclein.