Detection of Small Amounts of Misfolded α-Synuclein Identifies Early Parkinson's Disease

Parkinson's disease is characterized by misfolding and aggregation of α-synuclein, a pathology that spreads from where it initially starts, frequently in the intestinal nervous system, spreading between nerve cells. Researchers here report on a technique to identify the presence of small amounts of misfolded α-synuclein, demonstrating that it allows for early detection of the condition. Near every disease is easier to treat or at least slow down in its earlier stages, and early detection may well be an essential part of efforts to prevent the development of common age-related neurodegenerative conditions, such as Parkinson's disease.

Parkinson's disease is characterized by deposits of a protein known as alpha-synuclein (aSyn) in the nervous system. This protein can become corrupted and start to change shape in a process called misfolding. These misfolded proteins will start to clump together and poison the surrounding healthy nerve cells that are responsible for brain function, particularly for motor skills.

Protein Misfolding Cyclic Amplification (PMCA) - also termed seed amplification assay (SAA) technology - is under development at Amprion Inc., a biotech company focusing on the commercial utilization of SAA for early diagnosis of Parkinson's, Alzheimer's, and other neurodegenerative diseases. Researchers at Amprion studied 1,123 participants who were enrolled at 33 facilities globally between July 2010 and July 2019, representing the largest analysis so far of aSyn-SAA for the biochemical diagnosis of Parkinson's disease. Of these, 545 had Parkinson's disease, 163 were healthy people with no evidence of Parkinson's, 54 had evidence of the disease on brain scans, 51 were in the early stages of the disease, and 310 had genetic mutations that are known to cause Parkinson's but hadn't yet done so.

Using aSyn-SAA as a test in early Parkinson's detected the disease 87% of the time. Among participants who did not have Parkinson's, the test showed the absence of the disease 96% of the time. Interestingly, 30% of participants with the LRRK2 gene mutation - which causes a disease that looks like Parkinson's - do not have misfolded aSyn, but instead appear to have a different biological disease. In a group of patients who had lost their sense of smell, which is another sign of Parkinson's, the disease was detected 98.6% of the time. Significantly, 86% of prodromal, or pre-symptomatic, cases of Parkinson's disease were positive for aSyn-SAA years before clinical symptoms of the disease appeared, opening the door for an early diagnosis before substantial damage in the brain.

Currently, misfolded aSyn can only be detected by taking a spinal tap, which is an invasive and painful procedure. However, researchers are optimizing the aSyn-SAA technology to be utilized to detect the protein in blood, a skin biopsy, or a swab of the nose.