A DNA Aptamer That Detects Nerve Damage Could Make Alzheimer's Blood Tests Cheaper

The best current blood tests for Alzheimer's disease rely on antibodies. They work well, but antibodies are expensive to produce, vary between manufacturing batches, and are difficult to adapt for the compact biosensor platforms that could bring testing to a doctor's office or community clinic. A team at the Tokyo University of Science has built an alternative.

Published in Biochemical and Biophysical Research Communications in January 2026, the study reports the first DNA aptamers, short synthetic single-stranded DNA molecules, capable of binding neurofilament light chain (NfL) with affinity comparable to the antibodies used in current commercial tests. NfL is a structural protein released into the bloodstream when neurons are damaged, making it one of the most promising blood-based biomarkers for tracking neurodegeneration in Alzheimer's and other conditions.

What aptamers offer that antibodies do not

Antibodies are biological molecules produced by living cells. Each manufacturing run introduces slight variations, and the production process is expensive. Aptamers, by contrast, are chemically synthesized. They can be produced with minimal batch-to-batch variation, at lower cost, and with chemical modifications that allow them to attach directly to electrode surfaces, a critical requirement for building compact electrochemical biosensors.

The study was led by Associate Professor Kaori Tsukakoshi from the Department of Chemistry at the Tokyo University of Science, alongside second-year master's student Miyu Matsumoto and Distinguished Professor Kazunori Ikebukuro from the Tokyo University of Agriculture and Technology.

Seven rounds of molecular selection

The aptamers were developed using a process called SELEX (Systematic Evolution of Ligands by Exponential Enrichment). The method starts with a massive library of random DNA sequences, each a unique molecular shape. Over seven rounds of selection, sequences that bound to NfL were recovered and amplified, while those that stuck to unrelated molecules were discarded.

The process yielded 86 unique candidates. After removing sequences likely to form multimers and cause non-specific binding, 30 sequences remained that successfully recognized the full-length NfL protein. From that group, two stood out.

MN711 and MN734: the top performers

Aptamers MN711 and MN734 bound NfL with dissociation constants of 11 nanomolar and 8.1 nanomolar, respectively. In practical terms, that means they grip NfL tightly and specifically, with binding strength comparable to the antibodies in current commercial immunoassays like Simoa and Ella.

Specificity testing confirmed that the aptamers bound only NfL, not other Alzheimer's-related biomarkers like amyloid-beta or phosphorylated tau. The aptamers recognized a specific region of the NfL protein containing amino acid residues 281 to 338, a segment known to be present in the NfL fragments that circulate in human blood plasma.

Critically, the binding held up in human plasma. NfL concentrations in blood are extremely low, and plasma is a notoriously difficult matrix for molecular recognition because of the thousands of competing proteins. Demonstrating that the aptamers maintained their binding in this environment was essential for any diagnostic application.

The path toward point-of-care testing

Current NfL blood tests require specialized laboratory platforms that cost hundreds of thousands of dollars. They are confined to research hospitals and reference labs. The appeal of aptamer-based biosensors is that they could potentially be built into compact, inexpensive devices suitable for routine clinical screening.

Aptamers can be synthesized with terminal functional groups that allow straightforward immobilization onto metallic or carbon-based electrode surfaces. This compatibility with electrochemical sensing platforms means that MN711 and MN734 could, in principle, be integrated into handheld devices that measure NfL levels from a finger-prick blood sample.

Such devices do not yet exist for NfL. But the aptamers provide the molecular recognition component that would make them possible.

What still needs to happen

Developing aptamers that bind a target protein is the first step, not the last. Several gaps remain before this work translates into a usable diagnostic tool.

The study demonstrated binding affinity and specificity but did not build or test a complete biosensor device. The leap from a well-characterized aptamer to a functioning point-of-care test involves engineering challenges around signal transduction, sample preparation, calibration, and regulatory approval.

The aptamers were tested in spiked plasma samples, not in clinical samples from patients with confirmed Alzheimer's disease or other neurodegenerative conditions. Clinical validation with real patient samples across a range of disease stages and NfL concentrations is necessary.

NfL is also not specific to Alzheimer's disease. It rises in multiple sclerosis, traumatic brain injury, amyotrophic lateral sclerosis, and other conditions that damage neurons. Any NfL-based test would need to be interpreted alongside other clinical and biomarker information to be diagnostically useful for Alzheimer's specifically.

The research was supported by AMED under Grant Number JP22jm0210099 and the Yoshida Scholarship Foundation's master 21 program.