With aging populations on the rise, the need for better tools to diagnose and monitor Alzheimer's disease (AD), the most common cause of dementia, has never been more urgent. This disease is characterized by the gradual loss of nerve cells, a process known as neurodegeneration, which begins years before the onset of obvious symptoms. One way to detect this damage is to look for signs of injury to nerve cells. A key emerging biomarker of neurodegeneration is neurofilament light chain (NfL), a structural protein component of large nerve fibers. When neurons are injured, NfL escapes into the cerebrospinal fluid and eventually into the bloodstream, providing a window into ongoing neurodegeneration.
Leveraging the potential of NfL as a biomarker, researchers from Japan have developed the world's first aptamer (tiny, single-stranded synthetic DNA molecules) that can bind NfL with high affinity and specificity. These aptamers are cost-effective and can be manufactured to a consistently high standard, making them attractive components for next-generation biosensor technology and blood-based diagnostics.
This study was led by Associate Professor Kaori Tsukakoshi from the Department of Chemistry at the Tokyo University of Science, Japan, along with second-year master's student Ms. Miyu Matsumoto and Distinguished Professor Kazunori Ikebukuro from the Department of Biotechnology at the Tokyo University of Agriculture and Technology, Japan. Their work was made available online on December 16, 2025, and was published in Volume 796 of Biochemical and Biophysical Research Communications (BBRC) journal on January 18, 2026. These findings are the outcome of a joint UK–Japan research project supported by AMED-SICORP.
"We have reported the world's first DNA aptamer that binds to NfL, which is released into the blood in response to neurodegeneration in various neurodegenerative diseases. The developed aptamer has a binding affinity comparable to commercially available antibodies, and is expected to have a variety of applications in the future, such as diagnosing the progression of AD," says Assoc. Prof. Tsukakoshi.
The aptamers were generated through a process called the Systematic Evolution of Ligands by Exponential Enrichment (SELEX), in which vast libraries of random single-stranded DNA sequences are screened over repeated cycles so that only the strongest and most selective binders remain. The team performed seven rounds of selection where DNA strands that attached to NfL were recovered, amplified, and reused, while sequences that bound to unrelated tags were removed. This process yielded 86 unique aptamer candidates. After removing those that were likely to form multimers and cause non-specific binding, the team ended up with 30 promising sequences that successfully recognized the full-length NfL protein.
From this group, two aptamers, named MN711 and MN734, stood out. They bound to NfL with remarkable affinity, with binding dissociation constants of 11 nM and 8.1 nM, respectively, showing strength comparable to the antibodies currently used in commercial NfL tests. Furthermore, they were highly specific, binding only to NfL over other AD-related biomarkers like amyloid β and phosphorylated tau. Notably, the aptamers were found to recognize a specific region of the NfL protein containing amino acid residues 281–338, known to be present in fragments of NfL found in human blood plasma, providing additional evidence of their specific binding behavior. Critically, this binding ability was maintained even when the protein was mixed into human plasma despite its complex environment, suggesting potential for blood-based diagnosis.
Current blood tests for NfL rely on advanced immunoassay platforms that use pairs of antibodies to achieve high sensitivity. While effective, these antibody-based methods are expensive to produce, can vary from batch to batch, and are difficult to modify for use in newer types of biosensors. DNA aptamers offer an appealing alternative: they combine high affinity and specificity with the practical advantages of being chemically synthesized. This means they can be produced with minimal variation between batches, at a lower cost, and readily modified with chemical groups that allow them to attach to electrodes or other device surfaces, making them well suited for future biosensor applications.
"A key advantage of DNA aptamers is their compatibility with chemical modification. Aptamers can be synthesized with terminal functional groups that enable straightforward immobilization onto metallic or carbon-based electrode surfaces commonly used in electrochemical biosensors. This property allows aptamers such as MN711 and MN734 to be integrated into compact sensing platforms designed for point-of-care testing," concludes Assoc. Prof. Tsukakoshi.
