The new Alzheimer’s test is a candidate biomarker, miR-519a-3p. It is a microRNA (a tiny strand of genetic material) that rose in brain tissue even in the early, symptom-free stages of the disease. It is not a blood test yet. No clinical test based on it exists. Alzheimer’s is now among the top 10 causes of death and disability in the US, EU, and many other nations. Worse, despite huge effort, science still struggles to understand the disease. It does not fully know the causes, how the disease moves forward, or how it works inside the brain. Science does know a lot. The disease likely has many causes, not one. These include changes in the environment, toxins and chemicals, and metabolic disorders. Together they change the brain, stir up the immune system, and drive inflammation. That leads to a slow buildup of beta-amyloid and tau proteins. Both are harmful. As they pile up, they kill working brain cells. Dementia follows. When a person shows Alzheimer’s symptoms, like slipping thinking and trouble remembering, doctors order brain scans. They also test cerebrospinal fluid (CSF). The human brain is good at covering for damage. So symptoms show up only after much damage is done. By then, doctors can see brain changes on an MRI scan. They can also find changes in the CSF, the fluid around the brain and spinal cord. But these tests have problems. Studies show that Alzheimer’s probably begins 10-20 years before it is diagnosed. Brain scans miss early disease, when the changes are still too small to see. CSF testing has some value. But it is a poor test for early disease, because it takes a spinal puncture, a needle in the spine. CSF tests are also poor for screening. We need a test that catches Alzheimer’s early and can screen whole populations, such as a blood test. In a study published in the Biochimica et Biophysica Acta (BBA) – Molecular Basis of Disease, researchers described a candidate biomarker. It might one day help with early Alzheimer’s detection and screening.
Can Alzheimer’s be detected before symptoms start?
The study looked at the role of miR-519a-3p in Alzheimer’s disease (AD). This microRNA helps control which genes switch on in brain cells (neurons and glial cells). First, the researchers looked at how miR-519a-3p might affect PrPC protein. PrPC levels are known to rise and fall as AD moves forward. Its role in neurodegenerative (brain-wasting) diseases is disputed. Some studies say it protects the brain. Others say it may make damage to nerve cells worse. In their tests, miR-519a-3p seemed to lower PrPC protein levels. It did this by blocking the cell from building the protein, a process called translational repression. It did not break down the mRNA that codes for PrPC. This matters. It shows how miR-519a-3p might add to the molecular changes seen in AD. The second goal was to see if miR-519a-3p could work as an early marker for AD. The researchers found significantly increased miR-519a-3p in brain tissue taken after death from AD patients. The tissue came from the hippocampus and frontal cortex. This rise showed up even in the early, symptom-free stages of the disease. That is key, because it suggests miR-519a-3p could one day help catch AD before symptoms appear. These measurements were made in brain tissue, not in blood. MicroRNAs as a group stay stable and can be found in body fluids. That is why researchers see them as candidates for future non-invasive tests. But no one has shown yet that miR-519a-3p can be measured reliably in blood. No clinical test based on it exists yet. The study also found that miR-519a-3p levels were not significantly altered in other neurodegenerative diseases. These include other tauopathies (tau diseases) and synucleinopathies (the group of diseases that includes Parkinson’s disease). So the marker points to AD in particular. That makes a stronger case for miR-519a-3p as a reliable marker for early AD diagnosis.
The Bottom Line
It is still too early to say if this microRNA can catch AD early. But the findings are very encouraging. Larger studies must now show how precise this marker is. They must also show if it can be measured in blood or other body fluids. This study raises hope of catching Alzheimer’s very early. That means long before symptoms start and before brain cells die for good. If a reliable test comes from it, it may help prevent Alzheimer’s and lead to treatment.
Frequently asked questions
How do doctors test for Alzheimer’s today?
Once symptoms such as memory trouble and slipping thinking appear, doctors use brain scans like MRI. They also test cerebrospinal fluid, the fluid around the brain and spinal cord. Both work best after a lot of damage has already happened. Getting that fluid also takes a spinal puncture, a needle in the spine. So it is not practical for screening.
Why is Alzheimer’s so hard to catch early?
The brain is good at covering for damage. So symptoms show up only after much of the damage is done. Alzheimer’s probably begins 10 to 20 years before it is diagnosed. In those early years, the changes are too small for a brain scan to see. A spinal fluid test is too invasive to offer everyone as a screening tool.
Is there a blood test for Alzheimer’s based on this biomarker?
Not yet. The researchers measured miR-519a-3p in brain tissue after death, not in blood. MicroRNAs as a group stay stable in body fluids. That is why they are candidates for future non-invasive tests. No one has shown that this one can be measured reliably in blood. No clinical test built on it exists.
What causes Alzheimer’s disease?
Most likely many factors at once. These include changes in the environment, toxins and chemicals, and metabolic disorders. Together they change the brain, stir up the immune system and drive inflammation. That leads to a slow buildup of two harmful proteins, beta-amyloid and tau. They kill working brain cells and cause dementia.
Is miR-519a-3p specific to Alzheimer’s?
So far it looks that way. Levels were not significantly changed in other neurodegenerative (brain-wasting) diseases. These include other tau diseases and the synucleinopathies, the group that includes Parkinson’s disease. That is what makes it a promising marker. Larger studies still need to show how precise it is.
Source: Jácome, D., Cotrufo, T., Andrés-Benito, P., Lidón, L., Martí, E., Ferrer, I., del Río, J. A., & Gavín, R. (2024). miR-519a-3p, found to regulate cellular prion protein during Alzheimer’s disease pathogenesis, as a biomarker of asymptomatic stages. Biochimica et Biophysica Acta (BBA) – Molecular Basis of Disease, 1870(5), 167187. https://doi.org/10.1016/j.bbadis.2024.167187
Dr. Gurpreet Singh Padda, MD, MBA, MHP
