Tag: research

LBD Biomarkers: Progress

LBDA’s Research Centers of Excellence (RCOE) program presented a virtual symposium on “biomarkers” on January 25, 2021.  A biomarker is a biological sign that reveals the presence or severity of a disease.  For example, a biomarker of diabetes is “hemoglobin A1C”, which averages a person’s blood sugar levels over time, and suggests how well a person’s diabetes is being controlled.

Using Biomarkers in Research

Biomarkers are very important for the development of new treatments. A biomarker can be used to improve diagnostic certainty, which helps select the right participants for clinical trials. A biomarker can also serve as a “surrogate marker” of disease activity or severity. These can be used to show differences in outcomes between two groups of study participants: the group receiving the active drug compared to those receiving a placebo.

Biomarkers can be particularly important in diseases like Lewy body dementia (LBD), where diagnosis is challenging, or clinical outcomes vary. Researchers in LBDA’s RCOE program are very interested in identifying and validating biomarkers for use in LBD clinical trials.  (A validated biomarker means that the results have been independently reproduced in a separate study, confirming the reliability of the test.)

About the Symposium

As the pandemic forced the cancellation of many scientific meetings, opportunities to present new advances in LBD biomarkers have been limited. So LBDA organized a virtual event featuring eight internationally known scientists from Europe and the US. The event attracted over 200 scientists and physicians from academic centers, the National Institute of Health and the pharmaceutical industry.

Diagnostic Biomarker Progress

One of the most important goals for LBD research is to identify a biomarker to serve as a diagnostic test for Lewy bodies in the brain.  The speakers described promising efforts from spinal fluid tests, skin biopsies, and other biopsies.  The symposium also reviewed the reliability of these tests for diagnosis, and the potential to use some of these tests as markers of disease progression or severity. One of these tests is now commercially available for Parkinson’s disease, and another one will be offered starting in 2021.

Also of importance, many people with LBD also have brain changes related to Alzheimer’s disease; these changes are the presence of “plaques” and “tangles”.  Biomarker research in this area has also advanced rapidly in the past year. Blood tests for these types of brain changes have been validated and will also be commercially available soon, likely in the next calendar year.

These two advances will help LBD researchers to confirm that clinical trial participants have Lewy bodies in the brain and will also determine whether they have Alzheimer changes as well.

This helps improve clinical trials by including patients with more similar underlying microscopic changes in the brain. Another need from biomarkers is whether they can shed any light on mechanisms of disease that go beyond Lewy bodies, plaques and tangles.  These include measures of different functions of neurons (i.e., brain cells). A promising sample of research in this area was also reviewed and generated an animated discussion.

The LBD researchers are planning a summary of this meeting for a medical journal, and also plan to incorporate these biomarkers into studies intended to develop new treatments for LBD.

Promising Biomarkers

An effort is being made to create simple blood tests for these purposes, but in the meantime people with LBD who participate in clinical research studies will likely be invited soon to participate in skin biopsies and cerebrospinal fluid collection as part of these studies. These tests provide very important information that can help clinical trials be successful.

The Biomarker Symposium is a great example of how education and research on LBD has continued despite the COVID pandemic.  The LBDA has been pleased to be able to facilitate this type of program for the sake of improving the lives of our patients.

To view the recording of this 4 hour symposium, please visit our YouTube page, LBDAtv.



LBDA would like to thank Joseph Quinn, MD and David Irwin, MD for their help with this article.  

Sitting in the “genetic cross-hairs” of Alzheimer’s and Parkinson’s

Study locates five genes that may play a critical role in Lewy body dementia.

Source: National Institutes of Health

Genetic risk Diseases picture
An NIH-led genetic study found that Lewy body patients had higher chances of suffering Alzheimer’s or Parkinson’s disease than age-matched controls. Credit: Scholz lab NIH/NINDS.Scholz lab NIH/NINDS

In a study led by National Institutes of Health researchers, scientists found that five genes may play a critical role in determining whether a person will develop Lewy body dementia. The results supported the disease’s known ties to Parkinson’s disease and also suggested that people who have Lewy body dementia may share similar genetic profiles to those who have Alzheimer’s disease.

Most cases are considered ‘sporadic’, meaning there is no known genetic role; one theory is that the risk for developing LBD is driven by a combination of genetics and environmental factors. A growing body of evidence suggests genetics may play a role in LBD and that some cases may be inherited.

About the Study

Researchers compared the chromosomal DNA sequences of 2,981 people with LBD with those of 4,931 healthy, age-matched control participants. Initially, they found that the sequences of five genes from the people with LBD were often different from those of the controls. This suggested that these genes may be important.

It was the first time that two of the genes, called BIN1 and TMEM175, had been implicated in the disease. These genes may also have ties to Alzheimer’s and Parkinson’s diseases. The other three genes, SNCA, APOE, and GBA, had been implicated in previous studies, and thus, strengthened the importance of the genes in Lewy body dementia. The researchers were able to confirm these results by comparing the DNA sequences of another 970 people with LBD with a new set of 8,928 control subjects.

Further analysis suggested that changes in the activity of these genes may lead to dementia and that the GBA gene may have a particularly strong influence on the disease. The gene encodes instructions for beta-glucosylceramidase, a protein that helps a cell’s recycling system break down sugary fats. The researchers found that both common and rare variants in the GBA gene are tied to Lewy body dementia.

Comparing Genetic Risks with Alzheimer’s and Parkinson’s

Next, the researchers analyzed data from previous studies on Alzheimer’s and Parkinson’s disease. They found that the genetic profiles of the participants in this study had higher chances of suffering from either Alzheimer’s or Parkinson’s disease than the age-matched control subjects. These predictions held even after they lowered the potential impact of known Alzheimer’s and Parkinson’s disease-causing genes, like APOE and SNCA. Interestingly, the patient’s genetic risk profiles for Alzheimer’s disease, on the one hand, or Parkinson’s disease, on the other, did not overlap.

The senior author of the study, Sonja Scholz, M.D., Ph.D., is an investigator at the NIH’s National Institute of Neurological Disorders and Stroke (NINDS) and a member of LBDA’s Scientific Advisory Council. “Although Alzheimer’s and Parkinson’s disease are molecularly and clinically very different disorders, our results support the idea that the problems that cause those diseases may also happen in Lewy body dementia,” said Dr. Scholz. “The challenge we face in treating these patients is determining which specific problems are causing the dementia. We hope studies like this one will help doctors find precise treatments for each patient’s condition.”

New Research Resource

To help with this effort, the team published the genome sequence data from the study on the database of Genotypes and Phenotypes (dbGaP), a National Library of Medicine website that researchers can freely search for new insights into the causes of Lewy body dementia and other disorders.


Reference:  Chia, R., et al. Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into the complex genetic architecture. Nature Genetics, February 15, 2021 DOI: 10.1038/s41588-021-00785-3