One vial at a time, researchers at Brown analyze the mysteries of Alzheimer’s

In a new fluid biomarkers laboratory at Brown’s Carney Institute for Brain Science, researchers study blood samples for biological signals of Alzheimer’s disease and dementia, expanding the possibilities of brain research.

PROVIDENCE, R.I. [Brown University] — Inside a quiet, tucked-away lab in Brown University’s Biomedical Center sits an unassuming machine that, in the right hands, is helping unlock the secrets of the brain — specifically Alzheimer’s disease and related dementias.

With its clean lines and neon-colored panels, the machine resembles a futuristic refrigerator. It’s actually a technologically-advanced piece of laboratory equipment whose immunoassay analyzer detects biomarkers that — when combined with other tests — can serve as biological red flags for neurological conditions like Alzheimer’s.

Detection of biomarkers like these may make possible earlier diagnosis of Alzheimer’s, enabling patients to seek treatment even before they experience symptoms, said Kristine Pelton, the director of the Carney Institute for Brain Science’s Center for Alzheimer's Disease Research Fluid Biomarkers Laboratory. The brand-new facility is helping to transform fluid biomarker-based research at the University, the state and the region, she said.

“A non-invasive, reproducible and cost-effective way to detect and measure biomarkers is a game-changer for the field and for patients,” said Pelton, who noted that biomarkers will also allow researchers to monitor subtle changes in patients’ conditions over time, which can help them fine-tune treatment plans.

It’s very difficult to measure biomarkers for Alzheimer’s, which are generated by the central nervous system and found in cerebrospinal fluid and, in lesser concentrations, blood. The standard procedures involve a lumbar puncture (also known as a spinal tap) — which is time-consuming, expensive and painful for patients. Biomarkers can also be measured through imaging tests like an MRI or a PET scan, but these tests are not easily accessible for most people. 

But technology has been advancing to the point that immunoassay analyzers can now look for biomarkers in blood, which is much easier to obtain.

“If a doctor can order a simple blood test, the number of people that we can reach within our communities increases dramatically,” Pelton said. “In addition, by perfecting these blood-based biomarkers, we could potentially diagnose patients earlier when treatment interventions for neurodegeneration have a better chance at improving outcomes.”

Expanding Alzheimer’s research with cutting-edge technology

The Fluid Biomarkers Laboratory is a highly-anticipated component of the Center for Alzheimer’s Disease Research, the center on Brown’s campus dedicated to the study of Alzheimer’s disease and related dementias.

Founded in 2021 with gifts of $25 million and $5 million from donors who wish to remain anonymous, the joint center integrates the expertise of the Carney Institute for Brain Science and Brown’s Division of Biology and Medicine. Using tools like the new Quanterix Simoa HD-X Analyzer for immunoassay analysis will enable the facility to change experimental design and gather hard-to-obtain biological data.

Protein biomarkers such as beta-amyloid and tau are currently an area of intense research focus for their implications in Alzheimer’s disease.

Pelton came to Carney in March 2022 from the Dana Farber Cancer Institute and Boston Children’s Hospital. She jumped at the opportunity to build a state-of-the-art facility from the ground up in a geographic region that deeply needed what it would offer.

The Simoa HD-X is the only machine of its kind in the state, and one of a few in New England. Before its arrival, samples needed to be shipped out on dry ice, which ran the risk of loss or damage. What’s more, no single facility could run all of the different tests necessary for a comprehensive analysis. Months-long wait times and exorbitantly high cost estimates often rendered projects impossible — and research questions unanswerable. 

The Simoa HD-X Analyzer, from a biotech company called Quanterix, uses a proprietary bead-based technology in which a magnetic bead bonds to a biomarker to pull it out of a fluid sample. This technology allows for the detection of biomarkers if even a single molecule of that protein is present, making it 1,000 times more sensitive than previous models. Compared to other models that look for one biomarker at a time, the Simoa HD-X can measure up to six different biomarkers in one sample.

Now, researchers have the ability to partner with Pelton to design customized experiments. In consultations with researchers, she can develop assays, or biomarker tests that are unique to the client and project. The Simoa HD-X is fully automated and capable of analyzing up to 288 samples at a time, allowing it to churn through a large number of tests within three to four hours, compared to the day or two this process takes using standard protocols on less-advanced machines.

Bridging brain science and clinical treatment

The Center for Alzheimer’s Disease Research Fluid Biomarkers Laboratory is intended to serve as a bridge between basic laboratory science and clinical patient-focused research. Brain science research will be informed by direct access to patient-derived biomarkers and genetic data, and clinical researchers will have immediate knowledge of disease targets identified through basic research.

For example, Pelton is currently working on a project led by Dr. Frank Sellke, professor of cardiothoracic surgery at Brown’s Warren Alpert Medical School and the chief of cardiothoracic surgery at Rhode Island Hospital. Sellke’s team is investigating the relationship between neurocognitive and cardiac health — and Pelton is setting up a way for the facility to analyze blood samples for specific biomarkers related to neurocognitive injury, vascular injury and Alzheimer’s-related proteins. Costs and logistics made this type of complex investigation previously unfeasible; now, the researchers are able to do the experiment the way they want, on the Brown campus.

Looking ahead, one major focus of Pelton’s is to introduce new tests around the pTau217 biomarker, which research strongly suggests will be an effective method to distinguish Alzheimer’s disease from other forms of dementia and also pinpoint how far Alzheimer’s disease has advanced in a given sample. Pelton also intends to expand her staff so the facility can handle more clients at one time.

Since the facility opened in May, Pelton has collaborated with researchers and clinician scientists at Brown as well as Rhode Island Hospital, Butler Hospital, the University of Rhode Island as well as a pharmaceutical company and academic researchers in Maine and Texas. Pelton has already run tests analyzing a total of 1,058 samples — a drop in the bucket, one might say, of the exploding possibilities of this new fluid biomarker research facility.

Pelton recently attended an international conference about Alzheimer’s research where the consensus on blood-based biomarkers were that they were very important to the advancement of the field.

“There's a community here, in Southern New England, that hasn't had access to this type of technology and this type of biomarker research,” Pelton said. “It’s been very exciting to be able to help fulfill that need.”

Additional reporting by Corrie Pikul.