Overview

Parkinson’s disease is a degenerative neurological disorder in which the brain cells that normally produce the neurotransmitter dopamine die off. When these cells die, the brain loses its ability to control movement, which leads to tremors in the hands and feet. People with Parkinson’s disease may eventually lose their ability to walk and talk and can experience memory loss, behavioral differences, chronic pain, depression and fatigue. The Parkinson’s Foundation estimates that around 930,000 Americans live with the disease.

Parkinson’s disease tends to strike people age 60 and older; however, 5 to 10 percent of cases are “early onset.” The disease can be inherited, but the majority of cases are “spontaneous” with no apparent cause. Environmental factors, such as exposure to pesticides, have been linked to an increased risk of Parkinson’s disease.

Currently, there are no therapeutics to treat the root cause of the disease, but there are drugs to help relieve symptoms. Patients frequently receive a medication called levodopa, also called L-dopa, which nerve cells can use to boost the brain’s dopamine supply.

Our Approach

Researchers at La Jolla Institute for Immunology (LJI) are investigating how the immune system may contribute to Parkinson’s disease, and they hope to help develop better diagnostics and more effective therapies.

LJI Professor Alessandro Sette, Dr. Biol. Sci. and Research Assistant Professor Cecilia Lindestam Arlehamn, Ph.D., have uncovered evidence that Parkinson’s disease is indeed partly an autoimmune disease. 

In 2017, the researchers showed that clumps of a protein called alpha-synuclein can act as beacons for certain T cells, causing them to mistakenly attack brain cells and potentially contribute to the progression of Parkinson’s. This was the first direct evidence that autoimmunity could play a role in Parkinson’s disease.

In a 2020 study, the LJI team shed light on the timeline of T cell reactivity and disease progression. The researchers looked at blood samples from a large group of Parkinson’s disease patients and compared their T cells to a healthy, age-matched control group. They found that the T cells that react to alpha-synuclein are most abundant when patients are first diagnosed with the disease. These T cells tend to disappear as the disease progresses, and few patients still have them ten years after diagnosis. This research shows that signs of autoimmunity can appear in Parkinson’s disease patients years before their official diagnosis.

In 2022, Sette and Lindestam Arlehamn published research showing that people with Parkinson’s disease have memory T cells with a very specific gene signature, and genes associated with targeting alpha-synuclein may very well be causing ongoing inflammation in cases of Parkinson’s.

These breakthroughs could make it possible to someday detect Parkinson’s disease before the onset of debilitating motor symptoms—and potentially intervene with therapies to slow the disease progression.

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Research Projects

Lindestam Arlehamn
Neurodegenerative Diseases

The aim of this work funded by Aligning Science Across Parkinson’s (ASAP), in collaboration with Dr. Alessandro Sette, is to

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Sette
Parkinson’s

The lab investigates T cell reactivity and disease progression in Parkinson’s disease. Findings suggest immune cells are responsible for disease

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More research projects

Labs

Jan 6, 2022
Lindestam Arlehamn Lab

My laboratory is focused on understanding T cell immune responses to Mycobacterium tuberculosis and other infections, as well as self-antigens

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LJI Research Assistant Professor Cecilia Lindestam Arlehamn, Ph.D.
Cecilia Lindestam Arlehamn, Ph.D.
Research Assistant Professor
Center for Autoimmunity and Inflammation, Center for Sex-based Differences in the Immune System, Center for Vaccine Innovation
Jul 2, 2020
Sette Lab

Alessandro Sette, Dr.Biol.Sci., defines in chemical terms the specific structures (epitopes) that the immune system recognizes and uses this knowledge to measure and understand immune responses.

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Alessandro Sette, Dr.Biol.Sci.
Professor
Center for Autoimmunity and Inflammation, Center for Cancer Immunotherapy, Center for Vaccine Innovation