The sudden rise of Alzheimer’s has come as a surprise to researchers. It was among the rare diseases a little over a century ago. However, now Alzheimer’s is among the top 10 causes of mortality and disability in the US, EU, and many other nations. Further, what is worrisome is that despite so many efforts, science has been struggling to understand the disease. Science has not fully understood its causes, disease progress, and underlying mechanisms. Of course, science does know much. It is most likely caused by numerous factors, and not by one factor like environmental changes, exposure to toxins and chemicals, and also due to metabolic disorders. All of the above factors cause certain changes in the brain, immune responses, and inflammation, causing progressive accumulation of beta-amyloid and tau proteins. Both these are harmful proteins, and their accumulation in the brain causes the death of functioning brain cells, leading to dementia. When a person develops Alzheimer’s symptoms like cognitive decline and issues remembering things, doctors carry out brain scans and also analyze cerebrospinal fluid (CSF). The human brain is good at compensating things. Thus, Alzheimer’s symptoms develop when much brain damage has already occurred. Hence, when symptoms arise, doctors can visualize brain changes using an MRI scan or certain changes in the CSF fluid, a fluid that surrounds the brain and spinal cord. However, there are a few issues with these tests. Studies show that Alzheimer’s probably begins 10-20 years before its diagnosis. Brain scans are not good for early disease detection when brain changes are insufficient to visualize. CSF analysis has some value, but it is not a suitable test for early identification of the condition, as it requires carrying out a spinal puncture or inserting a needle in the spine. CSF tests are also not good for disease screening. There is a need to find a test that can detect Alzheimer’s early enough. A kind of test that is suitable for population-wide screening, like some kind of blood test. In a study published in the Biochimica et Biophysica Acta (BBA) – Molecular Basis of Disease, researchers described a candidate biomarker that might one day help with early Alzheimer’s detection and screening.
A New Biomarker May Help Identify Alzheimer’s in its Very Early Stages
The study investigated the role of miR-519a-3p in Alzheimer’s disease (AD). It is a type of microRNA that plays an important role in gene expression in various brain cells (neurons and glial cells). First, the researchers explored how miR-519a-3p might affect the levels of PrPC protein, which are known to fluctuate throughout the progression of AD. The role of PrPC in neurodegenerative diseases is controversial, with some studies suggesting it has a protective effect, while others argue it may enhance neurotoxicity. In their experiments, the researchers found that miR-519a-3p appears to reduce PrPC protein levels through a process known as translational repression rather than by degrading the mRNA that codes for PrPC. This finding is significant as it provides insight into how miR-519a-3p might contribute to the molecular changes observed in AD. The second focus of the study was on the potential of miR-519a-3p to serve as an early biomarker for AD. The researchers observed a significantly increased production of miR-519a-3p in post-mortem hippocampal and frontal cortex brain tissue from AD patients. Notably, this increase was present even in the early, asymptomatic stages of the disease. This discovery is crucial because it suggests that miR-519a-3p could one day help detect AD before clinical symptoms appear. These measurements were made in brain tissue, not in blood. MicroRNAs as a group are stable and detectable in body fluids, which is why researchers see them as candidates for future non-invasive tests. However, whether miR-519a-3p can be measured reliably in blood has not yet been shown, and no clinical test based on it exists yet. Additionally, the study found that miR-519a-3p levels were not significantly altered in other neurodegenerative diseases, such as other tauopathies and synucleinopathies (the group of diseases that includes Parkinson’s disease), highlighting its specificity for AD. This specificity strengthens the case for miR-519a-3p as a reliable biomarker for early AD diagnosis.
The Bottom Line
Although it is still early to say if this microRNA could help early AD detection, the findings are really encouraging. There is now a need for more extensive studies to understand how precise this new biomarker is and whether it can be measured in blood or other body fluids. The findings of this study raise hope of very early Alzheimer’s detection, much before its symptoms arise and irreversible brain cell death occurs. If a reliable test based on it can be developed, it may help prevent Alzheimer’s and find treatment for the condition. 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
