A New Tool for CSF-Based Parkinson Disease Diagnostics: Super-Resolution Microscopy Investigation of Alpha-Synuclein Aggregates
MJFF Research Grant, 2013
It is still difficult to diagnose Parkinson’s Disease (PD) patients through routine assays. Clinical research on PD suggests that the aggregation (clumping) of the protein alpha-synuclein is a good indicator of PD. The main difficulty is to identify the aggregates of synuclein, since these clumps of protein are much smaller than what a normal microscope can detect. We therefore propose here to use an improved microscope to identify synuclein aggregates, and thus provide an improved PD diagnostic method.
The field of optical microscopy has been revolutionized in the last few years, starting with the invention of so-called super-resolution microscopes in the early 2000’s. We have long been involved in this process, and we created optimal ways to prepare and analyze samples for this microscopy technology. We will use here super-resolution microscopy to detect and image synuclein aggregates in the cerebro-spinal fluid from PD patients and healthy control persons. We will compare the amount, the size and the shape of the aggregates between PD patients and controls, and we will thus verify which of these parameters can be used reliably as a diagnostic.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
This methodology, if successful, will allow clinicians to accurately identify PD patients. This method is relatively simple and should be more sensitive than many of the tests that are used today in clinical practice. It may also help to generate an earlier diagnosis than is possible today. The burden on the patients is minimal, since only a very small amount of cerebro-spinal fluid is needed for the assay.
We expect to provide a detailed analysis of PD patient and control samples, which will ideally provide a method that will allow clinicians to diagnose patients with confidence. For example, we will indicate which size or shape of synuclein aggregates is typical for PD patients. Medical doctors will then compare their results (obtained with a similar microscope) with our data and should be able to state whether the patient has PD or not.
Attending Physician at Movement Disorder Paracelsus-Elena-Klinik
ssistant Professor at University Medical Center, Goettingen
Location: Kassel, Germany
Head, Memory Clinic at University Medical Center Goettingen
German Center for Neurodegenerative Diseases, DZNE Goettingen
Location: Goettingen, Germany
Professor at University of Göttingen Medical Center
Location: , Germany