2023-04-26 00:03:38
Potential breakthrough: Thanks to a new test, Parkinson’s could be diagnosed before the typical symptoms appear. This is made possible by detecting the misfolded protein alpha-synuclein in the cerebrospinal fluid. In a recent study, the hit rate for patients with preliminary stages of the disease was between 63 and 97 percent. On average, 88 percent of those affected were correctly identified. This opens up the chance for an earlier and more accurate diagnosis, according to the researchers in “Lancet Neurology”.
Parkinson’s is the second most common neurodegenerative disease after Alzheimer’s. Typical of this is an accumulation of misfolded alpha-synuclein proteins in the brain, which leads to the death of nerve cells. Above all, the brain cells that produce the neurotransmitter dopamine are destroyed – the result is typical Parkinson’s symptoms such as tremors, slowed, reduced movements, but also cognitive losses and finally dementia.
Until now, Parkinson’s has often only been diagnosed when those affected notice the classic motor symptoms. By this time, however, the destruction of the dopamine-producing neurons is usually already advanced. However, the alpha-synuclein in the brain could not be determined directly.
Alpha-synuclein search in nerve water
In the future, however, it could be easier and earlier to diagnose Parkinson’s disease. Because a team led by Andrew Siderowf from the University of Pennsylvania in Philadelphia has developed a method with which the misfolded alpha-synuclein can be detected in brain water samples – even before Parkinson’s disease becomes noticeable through the first symptoms. This is made possible by a special test, the Alpha-Synuclein Seed Amplification Assay (SAA), which can detect the protein.
For their study, the researchers tested the procedure in a global multi-centre study with 1,123 participants. Of these, 545 suffered from Parkinson’s disease, 51 showed pre-forms such as sleep disorders or loss of smell and 310 carried genetic risk factors but were not yet ill. The remaining subjects formed the healthy control group. A small amount of cerebrospinal fluid was removed from all participants via a spinal cord puncture and tested for misfolded alpha-synuclein using the test.
High hit rate even in pre-forms of Parkinson’s
The result: The new test recognized a total of almost 88 percent of Parkinson’s cases – including many sufferers with preliminary stages of the disease. The test detected alpha-synuclein in the cerebrospinal fluid in around 97 percent of the participants with an impaired sense of smell and in 63 percent of the test subjects with a REM sleep disorder. In most of those affected, the detection was made before there was any evidence that the nerve cells in their substantia nigra were dying off.
The specificity of the alpha-synuclein test was around 96.3 percent. It indicates how many healthy controls were correctly identified as negative. The higher this rate, the lower the number of false positives. “Our results show that this method can identify people with Parkinson’s with high sensitivity and specificity,” state Siderowf and his colleagues. This accuracy also applies to patients with as yet unspecific signs.
“This result is a milestone for Parkinson’s research and a breakthrough in the field of biomarkers and for the development of new therapies,” comments Kathrin Brockmann, head of the Parkinson’s outpatient clinic at the University Hospital in Tübingen and board member of the German Society for Parkinson’s and Movement Disorders (DPG ) the study. Because the alpha-synuclein test makes it possible to detect Parkinson’s disease before the motor symptoms appear and thus very early on.
Different depending on the type of Parkinson’s
Detection of alpha-synuclein can also help distinguish between different forms of Parkinson’s. Depending on the genetic predisposition, the misfolded alpha-synuclein protein spreads in different ways and at different speeds in the brain and nervous system. “Since there are currently initial studies with vaccinations against misfolded forms of alpha-synuclein, it is important to predict which patients have this protein and drive the progression of the disease,” explains Brockmann.
Specifically, the study found that alpha-synuclein is detectable in 93 percent of patients with mutations in the GBA gene in the cerebrospinal fluid. In people with a Parkinson’s-promoting mutation in the LRRK2 gene, the hit rate was 78 percent, the team reports. In contrast, no misfolded alpha-synuclein was present in the cerebrospinal fluid of those affected with changes in the Parkin or PINK1 genes.
New opportunity for early detection and therapy
“With this test, we can now say directly for each patient individually whether the clumped alpha-synuclein is present. This not only significantly improves the diagnosis, but also the planning of Parkinson’s studies and ultimately the treatment of those affected,” says Brockmann. In their opinion, the alpha-synuclein test is therefore well suited for use as a screening test.
So far, the alpha-synuclein test has only been carried out with cerebrospinal fluid, but scientists are already working on test variants that also allow less invasive analyzes of blood, skin and mucous membranes. (Lancet Neurology, 2023; two: 10.1016/S1474-4422(23)00109-6)
Source: German Society for Parkinson’s and Movement Disorders
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