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University of Ghent Belgium Research Team Finds Stool Transplants Improve Motor Symptoms in Early-stage Parkinson’s Disease Patients

Findings could lead to clinical laboratory tests that help physicians identify microbes lacking in the microbiomes of their Parkinson patients

Microbiologists and clinical laboratory scientists know that gut microbiome can be involved in the development of Parkinson’s disease, a progressive neurological disorder that affects the nervous system due to damage caused to nerve cells in the brain. There is no cure for the illness. But a new treatment developed by researchers at the VIB Center for Inflammation Research at the University of Ghent in Belgium, may help to alleviate the symptoms.

During a clinical trial, VIB Center for Inflammation Research (VIB-IRC) scientists discovered that fecal microbiota transplantation (FMT), also known as a stool transplant, can improve motor skills in some Parkinson’s patients, according to Neuroscience News.

Parkinson’s disease (PD) develops when a protein called alpha-synuclein misfolds and forms into bundled clusters damaging nerve cells in the brain that produce dopamine. These formations, which are believed to appear in the gastrointestinal wall in the early stages of PD, then reach the brain via the vagus nerve leading to typical PD symptoms in patients.

Dopaminergic medication, deep brain stimulation, and speech and occupational therapy are some of the treatments currently available to people with Parkinson’s disease, but researchers are constantly on the lookout for more and better treatments,” Medical News Today reported.

The scientists published their findings in eClinicalMedicine titled, “Safety and Efficacy of Fecal Microbiota Transplantation in Patients with Mild to Moderate Parkinson’s Disease (GUT-PARFECT): A Double-Blind, Placebo-Controlled, Randomized, Phase 2 Trial.”

“Our study provides promising hints that FMT can be a valuable new treatment for Parkinson’s disease,” Roosmarijn Vandenbroucke, PhD (above), Principal Investigator, VIB-UGent Center for Inflammation Research and full professor, UGent Department of Biomedical molecular biology, Faculty of Sciences, told Neuroscience News. “More research is needed, but it offers a potentially safe, effective, and cost-effective way to improve symptoms and quality of life for millions of people with Parkinson’s disease worldwide.” Clinical laboratories will likely be involved in identifying the best microbes for the FMT treatments. (Photo copyright: University of Ghent.)

Correlation between Gut Microbiome and Neurogenerative Disease

To perform their clinical study—referred to as GUT-PARFECT—the IRC researchers first recruited patients with early-stage PD and healthy donors who provided stool samples to the Ghent Stool Bank. The PD patients received the healthy stool via a tube inserted into the nose which led directly into the small intestine.

The FMT procedures were performed on 46 patients with PD between December 2020 and December 2021. The participants in this group ranged in ages from 50 to 65. There were 24 PD patients in the placebo group, and a total of 22 donors provided the healthy stool. Clinical evaluations were performed at baseline, three, six, and 12 months.

After 12 months, the group that received the transplants showed a reduction in symptoms compared to the placebo group. Their motor score on the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) improved by a mean of 5.8 points. The improvement registered on the same scale for the placebo group was 2.7 points.

Developed in the 1980s, the MDS-UPDRS is a scale utilized to evaluate various aspects of PD by measuring patient responses via a questionnaire rating several issues (such as cognitive impairment, apathy, depression, and anxiousness) common in PD patients from normal to severe. It is divided into four parts:

  • Part I: Non-motor experiences of daily living.
  • Part II: Motor experiences of daily living.
  • Part III: Motor examination.
  • Part IV: Motor complications.

During the final six months of the research, the improvement in motor symptoms became even greater. To the VIB-IRC researchers this implied that an FMT may have long-lasting effects on PD patients. The FMT study group also experienced less constipation, a condition that can be bothersome for some PD patients.

“Our results are really encouraging!” said the study’s first author, Arnout Bruggeman, MD, PhD student, VIB-UGent Center for Inflammation Research, in a UGent News release. “After twelve months, participants who received the healthy donor stool transplant showed a significant improvement in their motor score, the most important measure for Parkinson’s symptoms.”

Findings Could Lead to Other Targeted Therapies for PD

The VIB-IRC researchers believe there is a correlation between the gut microbiome and Parkinson’s disease.

“Our findings suggested a single FMT induced mild, but long-lasting beneficial effects on motor symptoms in patients with early-stage PD. These findings highlight the potential of modulating the gut microbiome as a therapeutic approach and warrant a further exploration of FMT in larger cohorts of patients with PD in various disease stages,” the IRC researchers wrote in eClinicalMedicine.  

“Our next step is to obtain funding to determine which bacteria have a positive influence. This could lead to the development of a ‘bacterial pill’ or other targeted therapy that could replace FMT in the future,” Debby Laukens, PhD, Associate Professor, Ghent University, told Neuroscience News.

According to the Parkinson’s Foundation website, nearly one million people in the US live with PD. It is second only to Alzheimer’s disease in the category of neurodegenerative diseases.

More research and studies are needed before the VIB-IRC’s stool transplant treatment can be used in clinical care. As researchers learn more about which specific strains of bacteria are doing the beneficial work in PD patients, that data could eventually lead to clinical laboratory tests performed to help physicians identify which microbes are lacking in the microbiomes of their PD patients, and if fecal transplants could help those patients.

—JP Schlingman

Related Information:

Fecal Bacteria Transplant May Improve Parkinson’s Symptoms

Safety and Efficacy of Fecal Microbiota Transplantation in Patients with Mild to Moderate Parkinson’s Disease (GUT-PARFECT): A Double-Blind, Placebo-Controlled, Randomized, Phase 2 Trial

Stool Transplantation Shows Promise For Parkinson’s Disease

Fecal Microbiota Transplant Eases Parkinson’s Symptoms in Trial

Stool Transplant Could Improve Motor Symptoms in Parkinson’s Disease

In Conversation: Why Parkinson’s Research is Zooming in on the Gut

AXIM Biotechnologies Develops Diagnostic Test for Parkinson’s Disease That Uses Tear Drop Specimens and Returns Results in Less than 10 Minutes at the Point of Care

New non-invasive test could replace traditional painful spinal taps and clinical laboratory fluid analysis for diagnosis of Parkinson’s disease

Scientists at AXIM Biotechnologies of San Diego have added another specimen that can be collected non-invasively for rapid, point-of-care clinical laboratory testing. This time it is tears, and the diagnostic test is for Parkinson’s disease (PD).

The new assay measures abnormal alpha-synuclein (a-synuclein), a protein that is a biomarker for Parkinson’s, according to an AXIM news release which also said the test is the first rapid test for PD.

“The revolutionary nature of AXIM’s new test is that it is non-invasive, inexpensive, and it can be performed at a point of care. It does not require a lumbar puncture, freezing, or sending samples to a lab. AXIM’s assay uses a tiny tear drop versus a spinal tap to collect the fluid sample and the test can be run at a doctor’s office with quantitative results delivered from a reader in less than 10 minutes,” the news release notes.

A recent study conducted by the Michael J. Fox Foundation for Parkinson’s Research published in The Lancet Neurology titled, “Assessment of Heterogeneity among Participants in the Parkinson’s Progression Markers Initiative Cohort Using Α-Synuclein Seed Amplification: A Cross-Sectional Study,” found that “the presence of abnormal alpha-synuclein was detected in an astonishing 93% of people with Parkinson’s who participated in the study,” the news release noted.

“Furthermore, emerging evidence shows that a-synuclein assays have the potential to differentiate people with PD from healthy controls, enabling the potential for early identification of at-risk groups,” the news release continues. “These findings suggest a crucial role for a-synuclein in therapeutic development, both in identifying pathologically defined subgroups of people with Parkinson’s disease and establishing biomarker-defined at-risk cohorts.”

This is just the latest example of a disease biomarker that can be collected noninvasively. Other such biomarkers Dark Daily has covered include:

“With this new assay, AXIM has immediately become a stakeholder in the Parkinson’s disease community, and through this breakthrough, we are making possible new paradigms for better clinical care, including earlier screening and diagnosis, targeted treatments, and faster, cheaper drug development,” said John Huemoeller, CEO, AXIM (above), in a news release. Patients benefit from non-invasive clinical laboratory testing. (Photo copyright: AXIM Biotechnologies.)

Fast POC Test versus Schirmer Strip

AXIM said it moved forward with its novel a-synuclein test propelled by earlier tear-related research that found “a-synuclein in its aggregated form can be detected in tears,” Inside Precision Medicine reported.

But that research used what AXIM called the “outdated” Schirmer Strip method to collect tears. The technique involves freezing tear samples at -80 degrees Celsius (-112 Fahrenheit), then sending them to a clinical laboratory for centrifugation for 30 minutes; quantifying tear protein content with a bicinchoninic acid assay, and detecting a-synuclein using a plate reader, AXIM explained.

Alternatively, AXIM says its new test may be performed in doctors’ offices and offers “quantitative results delivered from a reader in less than 10 minutes.”

“Our proven expertise in developing tear-based diagnostic tests has led to the development of this test in record speed, and I’m extremely proud of our scientific team for their ability to expand our science to focus on such an important focus area as Parkinson’s,” said John Huemoeller, CEO, AXIM in the news release.

“This is just the beginning for AXIM in this arena,” he added. “But I am convinced when pharmaceutical companies, foundations, and neurologists see how our solution can better help diagnose Parkinson’s disease in such an expedited and affordable way, we will be at the forefront of PD research, enabling both researchers and clinicians a brand-new tool in the fight against PD.”

AXIM acquired Advanced Tear Diagnostics, Birmingham, Ala., in 2021. As part of this acquisition, it obtained two US Food and Drug Administration-cleared tests for dry eye syndrome, Fierce Biotech reported.

One of those tests was “a lateral flow diagnostic for point-of-care use that measures the level of lactoferrin proteins in tear fluid, which work to protect the surface of the eye. … Axim said that low lactoferrin levels have also been linked to Parkinson’s disease and that the assay can be used alongside its alpha-synuclein test,” Fierce Biotech noted.

Why Tears for PD Test?

Mark Lew, MD, Professor of Clinical Neurology, University of Southern California Keck School of Medicine, published earlier studies about using tear samples as biomarkers for Parkinson’s disease.

“It made sense to try and look at the proteinaceous [consisting of or containing protein] constituents of tear fluid,” Lew told Neurology Live. “Tear fluid is easy to collect. It’s noninvasive, inexpensive. It’s not like when you do a lumbar puncture, which is a much more involved ordeal. There’s risk of contamination with blood (saliva is dirty) issues with blood and collection. [Tear fluid analysis] is much safer and less expensive to do.”

In Biomarkers in Medicine, Lew et al noted why tears make good biomarkers for Parkinson’s disease, including “the interconnections between the ocular [eye] surface system and neurons affected in Parkinson’s disease.”

The researchers also highlighted “recent data on the identification of tear biomarkers including oligomeric α-synuclein, associated with neuronal degeneration in PD, in tears of PD patients” and discussed “possible sources for its release into tears.”

Future Clinical Laboratory Testing for Parkinson’s

Parkinson’s disease is the second most common neurodegenerative disorder after Alzheimer’s. It affects nearly one million people in the US. About 1.2 million people may have it by 2030, according to the Parkinson’s Foundation.

Thus, an accurate, inexpensive, non-invasive diagnostic test that can be performed at the point of care, and which returns clinical laboratory test results in less than 10 minutes, will be a boon to physicians who treat PD patients worldwide.

Clinical laboratory managers and pathologists may want to follow AXIM’s future research to see when the diagnostic test may become available for clinical use.

—Donna Marie Pocius

Related Information:

Parkinson’s Disease Biomarker Found

AXIM Biotechnologies Develops First Non-Invasive, Rapid, Point-of-Care, Diagnostic Test for Parkinson’s Disease

Assessment of Heterogeneity Among Participants in the Parkinson’s Progression Markers Initiative Cohort Using A-Synuclein Seed Amplification: a Cross-sectional Study

Tear Drop Test is First Rapid, Point-of-Care Diagnostic for Parkinson’s Disease

New Test Aims to Spot Signs of Parkinson’s Disease within a Tear Drop

Motivations for Using Tears to Confirm Parkinson’s Disease Diagnosis

Tears—More to Them than Meets the Eye: Why Tears are a Good Source of Biomarkers in Parkinson’s Disease

University of Gothenburg Study Findings Affirm Accuracy of Clinical Laboratory Blood Test to Diagnose Alzheimer’s Disease

Already-existing clinical laboratory blood test may be new standard for detecting Alzheimer’s biomarkers

In Sweden, an independent study of an existing blood test for Alzheimer’s disease—called ALZpath—determined that this diagnostic assay appears to be “just as good as, if not surpass, lumbar punctures and expensive brain scans at detecting signs of Alzheimer’s in the brain,” according to a report published by The Guardian.

Alzheimer’s disease is one of the worst forms of dementia and it affects more than six million people annually according to the Alzheimer’s Association. Clinical laboratory testing to diagnose the illness traditionally involves painful, invasive spinal taps and brain scans. For that reason, researchers from the University of Gothenburg in Sweden wanted to evaluate the performance of the ALZpath test when compared to these other diagnostic procedures.

Motivated to seek a less costly, less painful, Alzheimer’s biomarker for clinical laboratory testing, neuroscientist Nicholas Ashton, PhD, Assistant Professor of Neurochemistry at the University of Gothenburg, led a team of scientists that looked at other common biomarkers used to identify changes in the brain of Alzheimer’s patients. That led them to tau protein-based blood tests and specifically to the ALZpath blood test for Alzheimer’s disease developed by ALZpath, Inc., of Carlsbad, Calif.

The researchers published their findings in the journal JAMA Neurology titled, “Diagnostic Accuracy of a Plasma Phosphorylated Tau 217 Immunoassay for Alzheimer Disease Pathology.”

In their JAMA article, they wrote, “the pTau217 immunoassay showed similar accuracies to cerebrospinal fluid biomarkers in identifying abnormal amyloid β (Aβ) and tau pathologies.”

In an earlier article published in medRxiv, Ashton et al wrote, “Phosphorylated tau (pTau) is a specific blood biomarker for Alzheimer’s disease (AD) pathology, with pTau217 considered to have the most utility. However, availability of pTau217 tests for research and clinical use has been limited.”

Thus, the discovery of an existing pTau217 assay (ALZpath) that is accessible and affordable is a boon to Alzheimer’s patients and to the doctors who treat them.

“The ALZpath pTau217 assay showed high diagnostic accuracy in identifying elevated amyloid (AUC, 0.92-0.96; 95%CI 0.89-0.99) and tau (AUC, 0.93-0.97; 95%CI 0.84-0.99) in the brain across all cohorts. These accuracies were significantly higher than other plasma biomarker combinations and equivalent to CSF [cerebrospinal fluid] biomarkers,” an ALZpath press release noted.

“This is an instrumental finding in blood-based biomarkers for Alzheimer’s, paving the way for the clinical use of the ALZpath pTau217 assay,” stated Henrik Zetterberg, MD, PhD (above), Professor of Neurochemistry at the University of Gothenburg and co-author of the study. “This robust assay is already used in multiple labs around the globe.” Clinical laboratories may soon be receiving doctors’ orders for pTau217 blood tests for Alzheimer’s patients. (Photo copyright: University of Gothenburg.)

Study Details

Ashton’s team conducted a cohort study that “examined data from three single-center observational cohorts.” The cohorts included:

“Participants included individuals with and without cognitive impairment grouped by amyloid and tau (AT) status using PET or CSF biomarkers. Data were analyzed from February to June 2023,” the researchers wrote. 

These trials from the US, Canada, and Spain featured 786 participants and featured “either a lumbar puncture or an amyloid PET scan to identify signs of amyloid and tau proteins—hallmarks of Alzheimer’s disease,” The Guardian reported, adding that results of the University of Gothenburg’s study showed that the ALZpath pTau217 blood test “was superior to brain atrophy assessments, in identifying signs of Alzheimer’s.”

“80% of individuals could be definitively diagnosed on a blood test without any other investigation,” Ashton told The Guardian.

Diagnosis Needed to Receive Alzheimer’s Disease Treatments

“If you’re going to receive [the new drugs], you need to prove that you have amyloid in the brain,” Ashton told The Guardian. “It’s just impossible to do spinal taps and brain scans on everyone that would need it worldwide. So, this is where the blood test [has] a huge potential.”

Even countries where such drugs were not yet available (like the UK) would benefit, Ashton said, because the test, “Could potentially say that this is not Alzheimer’s disease and it could be another type of dementia, which would help to direct the patient’s management and treatment routine.”

However, Ashton himself noted the limitations of the new findings—specifically that there is no success shown yet in Alzheimer’s drugs being taken by symptom-free individuals.

“If you do have amyloid in the brain at 50 years of age, the blood test will be positive,” he said. “But what we recommend, and what the guidelines recommend with these blood tests, is that these are to help clinicians—so someone must have had some objective concern that they have Alzheimer’s disease, or [that] their memory is declining,” he told The Guardian.

Experts on the Study Findings

“Blood tests could be used to screen everyone over 50-years old every few years, in much the same way as they are now screened for high cholesterol,” David Curtis, MD, PhD, Honorary Professor in the Genetics, Evolution and Environment department at University College London, told The Guardian.

“Results from these tests could be clear enough to not require further follow-up investigations for some people living with Alzheimer’s disease, which could speed up the diagnosis pathway significantly in future,” Richard Oakley, PhD, Associate Director of Research and Innovation at the Alzheimer’s Society, UK, told The Guardian.

Though Oakley found the findings promising, he pointed out what should come next. “We still need to see more research across different communities to understand how effective these blood tests are across everyone who lives with Alzheimer’s disease,” he said.

“Expanding access to this highly accurate Alzheimer’s disease biomarker is crucial for wider evaluation and implementation of AD blood tests,” the researchers wrote in JAMA Neurology.

“ALZpath makers are in discussions with labs in the UK to launch it for clinical use this year, and one of the co-authors, Henrik Zetterberg, MD, PhD, Professor of Neurochemistry at the University of Gothenburg, is making the assay available for research use as part of the ‘biomarker factory’ at UCL,” The Guardian reported.

In the US, to be prescribed any of the available Alzheimer’s medications, a doctor must diagnose that the patient has amyloid in the brain. A pTau217 diagnostic blood test could be used to make such a diagnosis. Currently, however, the test is only available “for research studies through select partner labs,” Time reported.

“But later this month, doctors in the US will be able to order the test for use with patients. (Some laboratory-developed tests performed by certain certified labs don’t require clearance from the US Food and Drug Administration.),” Time added.

It may be that the University of Gothenburg study will encourage Alzheimer’s doctors in the UK and around the world to consider ordering pTau217 diagnostic blood tests from clinical laboratories, rather than prescribing spinal taps and brains scans for their Alzheimer’s patients.

—Kristin Althea O’Connor

Related Information:

New Study Published in JAMA Neurology Affirms High Diagnostic Accuracy of ALZpath’s pTau217 Test in Identifying Amyloid and Tau in the Brain

Blood Test Could Revolutionize Diagnosis of Alzheimer’s, Experts Say

Simple Blood Tests for Dementia to Be Trialed in NHS

A Blood Test for Alzheimer’s Disease Is Almost Here

Diagnostic Accuracy of a Plasma Phosphorylated Tau 217 Immunoassay for Alzheimer Disease Pathology

Alzheimer’s Disease Facts and Figures

Scientists Develop Blood Test for Alzheimer’s Disease

University of California San Francisco Study Finds Both High and Low Levels of High-Density Lipoprotein Cholesterol Associated with Increased Dementia Risk

If validated, study findings may result in new biomarkers for clinical laboratory cholesterol tests and for diagnosing dementia

Researchers continue to find new associations between biomarkers commonly tested by clinical laboratories and certain health conditions and diseases. One recent example comes from research conducted by the University of California San Francisco. The UCSF study connected cholesterol biomarkers generally used for managing cardiovascular disease with an increased risk for dementia as well.

The researchers found that both high and low levels of high-density lipoprotein (HDL)—often referred to as “good” cholesterol—was associated with dementia in older adults, according to a news release from the American Academy of Neurology (AAN).

UCSF’s large, longitudinal study incorporated data from 184,367 people in the Kaiser Permanente Northern California health plan. How the findings may alter cholesterol biomarker use in future diagnostics has not been determined.

The researchers published their findings in the journal Neurology titled, “Low- and High-Density Lipoprotein Cholesterol and Dementia Risk over 17 Years of Follow-up among Members of Large Health Care Plan.”

Maria Glymour, ScD

“The elevation in dementia risk with both high and low levels of HDL cholesterol was unexpected, but these increases are small, and their clinical significance is uncertain,” said epidemiologist Maria Glymour, ScD (above), study author and Professor of Epidemiology and Biostatistics at UCSF School of Medicine, in a news release. This is another example of how researchers are associating common biomarkers tested regularly by clinical laboratories with additional health conditions and disease states. (Photo copyright: University of California San Francisco.)

HDL Levels Link to Dementia Risk

The UCSF researchers used cholesterol measurements and health behavior questions as they tracked Kaiser Permanente Northern California health plan members who were at least 55 years old between 2002 and 2007, and who did not have dementia at the time of the study’s launch.

The researchers then followed up with the study participants through December 2020 to find out if they had developed dementia, Medical News Today reported.

“Previous studies on this topic have been inconclusive, and this study is especially informative because of the large number of participants and long follow-up,” said epidemiologist Maria Glymour, ScD, study author and Professor of Epidemiology and Biostatistics at UCSF School of Medicine, in the AAN news release. “This information allowed us to study the links with dementia across the range of cholesterol levels and achieve precise estimates even for people with cholesterol levels that are quite high or quite low.” 

According to HealthDay, UCSF’s study findings included the following:

  • More than 25,000 people developed dementia over about nine years. They were divided into five groups.
  • 53.7 milligrams per deciliter (mg/dL) was the average HDL cholesterol level, amid an optimal range of above 40 mg/dL for men and above 50 mg/dL for women.
  • A 15% rate of dementia was found in participants with HDL of 65 mg/dL or above.
  • A 7% rate of dementia was found in participants with HDL of 11 mg/dL to 41 mg/dL.

“We found a U-shaped relationship between HDL and dementia risk, such that people with either lower or higher HDL had a slightly elevated risk of dementia,” Erin Ferguson, PhD student of Epidemiology at UCSF, the study’s lead study author, told Medical News Today.

What about LDL?

The UCSF researchers found no correlation between low-density lipoprotein (LDL)—often referred to as “bad” cholesterol”—and increased risk for dementia. But the risk did increase slightly when use of statin lipid-lowering medications were included in the analysis.

“Higher LDL was not associated with dementia risk overall, but statin use qualitatively modified the association. Higher LDL was associated with a slightly greater risk of Alzheimer’s disease-related dementia for statin users,” the researchers wrote in Neurology.

“We found no association between LDL cholesterol and dementia risk in the overall study cohort. Our results add to evidence that HDL cholesterol has similarly complex associations with dementia as with heart disease and cancer,” Glymour noted in the AAN news release.

Australian Study also Links High HDL to Dementia

A separate study from Monash University in Melbourne, Victoria, Australia, found that “abnormally high levels” of HDL was also associated with increased risk for dementia, according to a Monash news release.

The Monash study—which was part of the ASPREE (ASPpirin in Reducing Events in the Elderly) trial of people taking daily aspirin—involved 16,703 Australians and 2,411 Americans during the years 2010 to 2014. The researchers found:

  • 850 participants had developed dementia over about six years.
  • A 27% increased risk of dementia among people with HDL above 80 mg/dL and a 42% higher dementia risk for people 75 years and older with high HDL levels.

These findings, Newsweek pointed out, do not necessarily mean that high levels of HDL cause dementia. 

“There might be additional factors that affect both these findings, such as a genetic link that we are currently unaware of,” Andrew Doig, PhD, Professor, Division of Neuroscience at University of Manchester, told Newsweek. Doig was not involved in the in the Monash University research.

Follow-up research could explore the possibility of diagnosing dementia earlier using blood tests and new biomarkers, Newsweek noted.

The Australian researchers published their findings in The Lancet Regional Health-Western Pacific titled, “Association of Plasma High-Density Lipoprotein Cholesterol Level with Risk of Incident Dementia: A Cohort Study of Healthy Older Adults.”

Cholesterol Lab Test Results of Value to Clinical Labs

If further studies validate new biomarkers for testing and diagnosis, a medical laboratory’s longitudinal record of cholesterol test results over many years may be useful in identifying people with an increased risk for dementia.

Clinical pathologists and laboratory managers will want to stay tuned as additional study insights and findings are validated and published. Existing laboratory testing reference ranges may need to be revised as well.

As well, the findings of this UCSF research demonstrate that, in this age of information, there will be plenty of opportunities for clinical lab scientists and pathologists to take their labs’ patient data and combine it with other sets of data. Digital tools like artificial intelligence (AI) and machine learning would then be used to assess that large pool of data and produce clinically actionable insights. In turn, that positions labs to add more value and be paid for that value.

—Donna Marie Pocius

Related Information:

Both High and Low HDL Cholesterol Tied to Increased Risk of Dementia

Low-and High-Density Lipoprotein Cholesterol and Dementia Risk over 17 Years of Follow-up among Members of a Large Health Care Plan

Both High and Low HDL Cholesterol Tied to Slight Increase in Risk of Dementia

How HDL “Good” Cholesterol Might Raise Dementia Risk

HDL vs. LDL Cholesterol

How Levels of “Good” Cholesterol May Increase Dementia Risk

High Levels of “Good Cholesterol” May Be Associated with Dementia Risk, Study Shows

Association of Plasma High-Density Lipoprotein Cholesterol Level with Incident Dementia: A Cohort Study of Healthy Older Adults

Study Claims High Good Cholesterol Levels Linked to Greater Dementia Risk

Researchers at Stanford University Discover Gene Variant That Appears to Protect Individuals from Both Alzheimer’s and Parkinson’s Disease

Study findings may lead to new clinical laboratory tests, as well as vaccines and immunotherapies for neurodegenerative diseases

Research into the human genome continues to produce useful new insights. This time, a study led by researchers at Stanford University identified a genetic variation that is believed to help “slow or even stall” progression of neurodegenerative diseases, including Alzheimer’s and Parkinson’s, according to a press release. Because these genetic variations are common, it is likely that diagnostic tests can be developed for use by clinical laboratories.

Researchers at Stanford Medicine led the study which discovered that approximately one in five individuals carry the gene variant, a protective allele identified as DR4 (aka, HLA-DR4). It’s one of a large number of alleles found in a gene known as DRB1.

DRB1 is part of a family of genes collectively known as the human lymphocyte antigen complex or HLA. The HLA-DRB1 gene plays a crucial role in the ability of the immune system to see a cell’s inner contents.

The Stanford scientists published their findings in the journal PNAS titled, “Multiancestry Analysis of the HLA Locus in Alzheimer’s and Parkinson’s Diseases Uncovers a Shared Adaptive Immune Response Mediated by HLA-DRB1*04 Subtypes.” Approximately 160 researchers from roughly 25 countries contributed to the work. 

Emmanuel Mignot, MD, PhD

“In an earlier study, we’d found that carrying the DR4 allele seemed to protect against Parkinson’s disease,” said Emmanuel Mignot, MD, PhD (above), Director of the Stanford Center for Narcolepsy, in a Stanford press release. “Now, we’ve found a similar impact of DR4 on Alzheimer’s disease.” Clinical laboratories may soon have new vaccines for both neurodegenerative diseases. (Photo copyright: Stanford University.)


DR4 Found to Impact Both Parkinson’s and Alzheimer’s Diseases

To perform their research, the team examined a large collection of medical and genetic databases from 176,000 people who had either Alzheimer’s or Parkinson’s disease. The people involved in the study were from numerous countries located in East Asia, Europe, the Middle East and South America. Their genomes were then compared with people who did not have the diseases, focusing on the incidence and age of onset.

“In an earlier study we’d found that carrying the DR4 allele seemed to protect against Parkinson’s disease,” said Mignot in the Stanford press release. “Now, we’ve found a similar impact of DR4 on Alzheimer’s disease.”

The team found that about 20% to 30% of people carry DR4, and that they have around a 10% risk reduction for developing the two diseases. 

“That this protective factor for Parkinson’s wound up having the same protective effect with respect to Alzheimer’s floored me,” said Emmanuel Mignot, MD, PhD, the Craig Reynolds Professor of Sleep Medicine in the Department of Psychiatry and Behavioral Sciences at Stanford University and the Director of the Stanford Center for Narcolepsy, in the Stanford Medicine press release. “The night after we found that out, I couldn’t sleep.”

The scientists also analyzed data from autopsied brains of more than 7,000 Alzheimer’s patients and discovered that individuals who carry DR4 had fewer neurofibrillary tangles and that those tangles are composed mainly of modified tau proteins, a common biomarker for Alzheimer’s.

The presence of these tangles corresponds with the severity of Alzheimer’s disease. They are not typically seen in Parkinson’s patients, but the Stanford team found that Parkinson’s patients who did carry DR4 experienced later onset of symptoms.

Mignot stated that tau, which is essential in Alzheimer’s, may also play a role in Parkinson’s, but that further research is required to prove its function.

Both diseases are characterized by the progressive loss of certain nerve cells or neurons in the brain and are linked to an accumulation of abnormal proteins. The Stanford researchers suggested that the DR4 gene variant may help protect individuals from Alzheimer’s and Parkinson’s by preventing the buildup of tau proteins.

“This is a very interesting study, providing additional evidence of the involvement of the immune system in the pathogenesis of Alzheimer’s and Parkinson’s,” neurologist Wassim Elyaman, PhD, Assistant Professor of Neurological Sciences in Neurology, the Taub Institute and the Institute for Genomic Medicine at Columbia University, told Live Science.

New Vaccines and Immunotherapies

According to the Alzheimer’s Association, more than six million Americans are currently living with Alzheimer’s disease and approximately one in three Americans die with Alzheimer’s or another dementia. 

The Parkinson’s Foundation states that nearly one million Americans are currently living with Parkinson’s disease, and that number is expected to rise to 1.2 million by 2030. Parkinson’s is the second-most common neurodegenerative disease after Alzheimer’s disease.

Even though the genetic analysis of the Stanford research is strong, more immune cell and blood-based research is needed to definitively establish how tau is connected to the two diseases.

This research could have implications for clinical laboratories by giving them biomarkers for a useful new diagnostic test, particularly for diagnosing Alzheimer’s and Parkinson’s.

Further, Mignot suggested that an effective vaccine could delay the onset or slow the progression of both diseases. He hopes to test his hypothesis on genetically modified mice and eventually human subjects.

—JP Schlingman

Related Information:

Stanford Medicine-led Study Finds Genetic Factor Fends Off Alzheimer’s and Parkinson’s

Gene Variant Carried by One in Five People May Guard Against Alzheimer’s and Parkinson’s, Massive Study Finds

Multiancestry Analysis of the HLA Locus in Alzheimer’s and Parkinson’s Diseases Uncovers a Shared Adaptive Immune Response Mediated by HLA-DRB1*04 Subtypes

Alzheimer’s Disease: Tau Biology and Pathology

Tau Protein and Alzheimer’s Disease: What’s the Connection?

C₂N Diagnostics Releases PrecivityAD, the First Clinical Laboratory Blood Test for Alzheimer’s Disease

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