July 11, 2017

Immune response linked to Parkinson’s disease

At a Glance

  • Researchers found that immune cells recognize and react to alpha-synuclein, the protein that builds up in the brains of people with Parkinson’s disease.
  • These findings suggest that the immune system may play a role in the start or progression of Parkinson’s disease. 
Volunteer visiting senior man with a cane Researchers have been trying to understand why deposits of the protein alpha-synuclein form in the brain cells of people with Parkinson’s disease and what role they play in the disease. BananaStock/Thinkstock

Parkinson’s disease is a degenerative brain disorder that develops when nerve cells in the brain become impaired and eventually die. As these brain cells die, people with Parkinson’s disease may start experiencing involuntary shaking, muscle stiffness, slowed movements, problems with balance, and other symptoms. At first, only a tremor in one hand may be noticeable. As the disease advances, people may have trouble talking, getting dressed, and walking. There’s no cure for the disease, but medicines or surgery can help with managing symptoms.

The affected brain cells of people with Parkinson’s disease contain Lewy bodies—deposits consisting mainly of an abnormal form of a protein called alpha-synuclein. Researchers don’t yet know why Lewy bodies form or what role they play in the disease. Some animal studies suggest that abnormal alpha-synuclein can trigger an immune response from T cells. These cells help the immune system destroy and remove foreign matter, but become problematic when they mistakenly attack the body’s own cells. T cells have also been found in the brains of people with Parkinson’s disease. These findings suggested a connection between alpha-synuclein and immune responses.

To explore this possible connection, a team of researchers led by Drs. David Sulzer of the Columbia University Medical Center and Alessandro Sette of the La Jolla Institute for Allergy and Immunology carried out a study comparing T cell responses to alpha-synuclein in people with Parkinson’s disease and healthy volunteers. The study was supported in part by NIH’s National Institute of Neurological Disorders and Stroke (NINDS). Results were published in Nature on June 29, 2017.

The scientists collected blood samples from 67 people with Parkinson’s disease and 36 healthy adults. They exposed the samples to various synthetic alpha-synuclein peptides. Each peptide represented a different fragment of the alpha-synuclein molecule. This allowed the scientists to map which regions of the protein elicit immune responses.

Samples taken from people with Parkinson’s disease were far more likely than samples taken from healthy adults to show strong immune responses to the alpha-synuclein fragments. Two fragments, containing the S129 and Y39 regions of the alpha-synuclein protein, provoked the highest T cell responses among people with Parkinson’s disease. These findings suggest that people with Parkinson’s disease have a heightened immune response to alpha-synuclein.

“The idea that a malfunctioning immune system contributes to Parkinson’s dates back almost 100 years,” Sulzer says. “But until now, no one has been able to connect the dots. Our findings show that two fragments of alpha-synuclein, a protein that accumulates in the brain cells of people with Parkinson’s, can activate the T cells involved in autoimmune attacks.”

“It remains to be seen whether the immune response to alpha-synuclein is an initial cause of Parkinson’s or if it contributes to neuronal death and worsening symptoms after the onset of the disease,” Sette explains. “These findings, however, could provide a much-needed diagnostic test for Parkinson’s disease and could help us to identify individuals at risk or in the early stages of the disease.”

—by Geri Piazza

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References: T cells from patients with Parkinson's disease recognize α-synuclein peptides. Sulzer D, Alcalay RN, Garretti F, Cote L, Kanter E, Agin-Liebes J, Liong C, McMurtrey C, Hildebrand WH, Mao X, Dawson VL, Dawson TM, Oseroff C, Pham J, Sidney J, Dillon MB, Carpenter C, Weiskopf D, Phillips E, Mallal S, Peters B, Frazier A, Lindestam Arlehamn CS, Sette A. Nature. 2017 Jun 29;546(7660):656-661. doi: 10.1038/nature22815. Epub 2017 Jun 21. PMID: 28636593.

Funding: NIH’s National Institute of Neurological Disorders and Stroke (NINDS) and National Institute on Aging (NIA); the JPB, William F. Richter, Michael J. Fox, and Parkinson’s Foundations; and the AHMMRF, JHH, and JHUSOM Parkinson’s disease program.