Neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and ALS affect millions of people worldwide, often robbing them of memory, movement, or independence. For decades, diagnosis has relied heavily on symptoms that only emerge once significant brain damage has already occurred. But today, a wave of scientific discoveries is reshaping how we approach early detection and treatment.
In this episode of Tiny Expeditions, HudsonAlpha researchers Ben Henderson, PhD, and Bri Rogers, PhD, joined us to discuss the cutting‑edge science behind biomarkers, genetic risk factors, and why basic research is critical for breakthroughs in treating these devastating disorders.
Behind the Scenes
Meet Our Guests
Dr. Benjamin Henderson
Ben Henderson, PhD, is a Senior Scientist in the Myers lab at HudsonAlpha. Ben leads projects searching for genomic biomarkers of ALS and Parkinson’s disease. His work focuses on small RNAs, tiny but powerful molecules that may one day form the basis of a simple blood test to detect disease years earlier than current methods allow.
Dr. Bri Rogers
Bri Rogers, PhD, is a postdoctoral associate in the Cochran lab at HudsonAlpha. Bri’s work explores how genetic variants influence dementia, from rare mutations that cause early-onset Alzheimer’s to more common variants that subtly influence disease risk. Her research on gene regulation and tau protein lays important groundwork for developing new therapeutic strategies.
Why are neurodegenerative diseases so hard to diagnose and treat?
Neurodegenerative diseases occur when neurons in the brain are damaged over time, often due to toxic protein clumps that disrupt normal function. Unlike other cell types in the body, neurons cannot be easily replaced once lost, making these diseases progressive and irreversible.
Challenges in diagnosis:
- Overlapping symptoms: Memory loss, movement disorders, or speech changes often look similar across different conditions.
- Long “diagnostic odyssey”: It can take years and multiple specialists before an individual receives a clear answer.
- Subjective clinical signs: Early stages may be subtle and require expert interpretation.
Challenges in treatment:
- Late detection: By the time symptoms are obvious, significant neuron loss has already occurred.
- Complex cause: These diseases arise from a mixture of genetic, environmental, and age-related factors (for more info on this, check out Episode 1)
- Limited drug targets: Treatments often focus on symptoms rather than underlying causes.
The Role of Biomarkers in Brain Health
What is a biomarker?
A biomarker is a measurable indicator of biological health. Some common examples you’ve likely encountered at your doctor’s office include blood pressure, cholesterol levels, and blood sugar (A1C levels). They provide a snapshot of how your body is functioning at a given point in time.
Why are they important in neurodegeneration?
Traditionally, confirming Alzheimer’s disease or Parkinson’s disease required brain scans or even postmortem brain tissue. Now, blood-based biomarkers provide a simpler and less invasive option for detecting disease at its earliest stages.
Currently, there are a few FDA-approved biomarkers for Alzheimer’s disease, including:
- p-tau217: a blood test that measures levels of the protein p-tau217 in your plasma. Along with other tests and medical history, it can help diagnose Alzheimer’s disease.
- A test of p-tau217 in combination with another test for amyloid beta 42 (another Alzheimer’s-associated protein) was recently FDA-approved and can be ordered by your physician.
At HudsonAlpha, researchers like Ben Henderson are exploring small RNAs as potential biomarkers. These tiny molecules regulate cell processes and may reveal when something is wrong in brain biology. The lab collaborates with clinics, such as Crestwood Medical Center’s ALS Care Clinic, to collect patient blood samples.
By analyzing the samples, they’ve identified specific RNA signatures that may distinguish patients from healthy controls. Imagine walking into a clinic, giving a simple blood sample, and receiving insights about risk levels, something that was once science fiction is becoming reality.
Genetics: Unlocking the Cause of Disease
While biomarkers improve diagnosis, genetics helps explain why these diseases develop in the first place.
Dr. Bri Rogers focuses on understanding genetic variants that influence dementia. Her work sheds light on both rare mutations that strongly predict early onset disease and more common variants that subtly increase risk when combined.
For example:
- Rare mutations in genes like APP (amyloid precursor protein) or PSEN1/2 can cause Alzheimer’s to appear decades earlier than normal.
- More common variants in the gene APOE, especially the APOE‑ε4 allele, increase risk for late‑onset Alzheimer’s by affecting how amyloid plaques are cleared from the brain.
Much of this research also involves regulatory DNA, the areas of our genome that don’t make proteins directly but control when and how genes are turned on. Bri’s recent work on the MAPT gene, which produces the tau protein involved in brain tangles, identified switch‑like elements that determine tau levels in neurons. These insights are already laying the groundwork for therapeutic targets.
Why Basic Science is the Foundation
Ben and Bri both emphasized an important point: none of these advances would exist without basic research. Breakthroughs often begin with the slow, careful process of foundational research. Before a diagnostic test can reach the clinic or a drug can be approved by the FDA, scientists must map out the biology at the molecular level.
Discovering genetic variants, decoding RNA biology, or understanding how tau tangles form might sound far removed from the clinic, but these foundational insights fuel the progress behind blood tests, clinical trials, and potential therapies.
This kind of basic science is at the heart of HudsonAlpha’s mission. From sequencing small RNAs to mapping gene regulation, these studies provide the knowledge industry relies on to develop diagnostics and therapies. While it may not make headlines every day, it’s the essential groundwork for the future of brain health.