A new era in Alzheimer’s detection: KRISS’s ultrasensitive diagnostic platform

The Korea Research Institute of Standards and Science (KRISS, President Lee Ho Seong) has developed a diagnostic platform that amplifies the unique optical signals of molecules by more than a hundred million times, enabling the precise detection and quantification of trace amounts of Alzheimer’s disease biomarkers in body fluids. With a simple body fluid test, the platform can quantify multiple biomarkers with ultrasensitivity and high reliability, complementing conventional imaging-based diagnostics and enabling early diagnosis and monitoring of disease progression.

Alzheimer’s disease is a leading degenerative brain disorder in which neurons in the brain gradually deteriorate, causing progressive decline in cognitive functions such as memory and reasoning. It accounts for roughly 60–70% of dementia cases worldwide, and with no fundamental cure currently available, early diagnosis and continuous management are essential.

At present, Alzheimer’s disease is primarily diagnosed using imaging modalities such as PET* and MRI**. However, each examination can cost over 1 million KRW (approximately USD 750) and requires specialized facilities. Moreover, these imaging techniques can only detect the disease once it has progressed beyond a certain stage, making early detection difficult.
_{* PET (Positron Emission Tomography): A nuclear medicine imaging technique that visualizes functional and biochemical changes inside the body by injecting a radiopharmaceutical and detecting its distribution.
** MRI (Magnetic Resonance Imaging): A non-invasive imaging method that uses strong magnetic fields and radio frequency pulses to generate high-resolution images of soft tissues and blood vessels without the need for contrast agents.}

Simpler body fluid tests have so far lacked sufficient accuracy, preventing them from being used as reliable diagnostic tools.
Two peptides found in the brain—amyloid beta (Aβ) 42 and Aβ 40—are closely associated with Alzheimer’s disease. Measuring their concentrations in body fluids and calculating the Aβ42/Aβ40 ratio enables early assessment of disease progression.

However, with the detection performance of conventional enzyme-linked immunosorbent assay (ELISA) methods, it has been difficult to simultaneously and accurately detect these two peptides in ultra-low concentrations present in blood, cerebrospinal fluid, and other body fluids.
^{* Peptide: A short chain of amino acids linked by peptide bonds, representing an intermediate between amino acids and proteins, and playing key roles in regulating various biological functions.
** Amyloid beta (Aβ): The main component of amyloid plaques found in the brains of Alzheimer’s patients. Composed of 36–43 amino acids, Aβ is derived from amyloid precursor protein (APP) through cleavage by β-secretase and γ-secretase, and is known to cause neurotoxicity that contributes to disease onset.
*** ELISA (Enzyme-Linked Immunosorbent Assay): A biochemical method widely used in laboratories to detect and quantify specific substances based on antigen–antibody interactions and enzyme-mediated signal generation.}

The Medical Metrology Group at KRISS has developed an ultrasensitive multiplexed quantitative sensing platform based on Surface-Enhanced Raman Spectroscopy (SERS), which is over 100,000 times more sensitive than conventional ELISA methods and capable of accurately distinguishing and quantifying multiple biomarkers.

SERS is an analytical technique that greatly amplifies the unique optical signals generated when light interacts with molecules by using metallic nanostructures, enabling the precise detection of even trace amounts of molecules.

The research team developed distinct, multi-type gold nanoparticles with a sunflower-shaped cross-section, capable of producing strong and uniform SERS signals from individual particles. This design overcomes the issue of signal non-uniformity caused by variations in interparticle spacing in conventional spherical gold nanoparticles.

By creating a high-density, uniform distribution of signal enhancement sites both inside and on the surface of each particle, the nanoparticles generate strong and highly reproducible signals even at the single-particle level. As a result, the platform achieves excellent quantitative performance proportional to the concentration of target molecules, while enabling the simultaneous detection of multiple distinct targets.

Using the multiplex SERS nanoparticles, each assigned a unique optical ID, the researchers successfully quantified ultra-trace levels of Aβ42 and Aβ40 at concentrations as low as 8.7 × 10⁻17 g/mL and 1.0 × 10⁻15 g/mL, respectively. This represents world-leading performance in terms of both sensitivity and dynamic detection range for multiplex quantitative analysis.

Dr. You Eun-Ah, Principal Research Scientist at the KRISS Medical Metrology Group, stated,

“The sensing platform we have developed can be mass-produced at low cost and flexibly adapted to a wide range of biomarkers.

Beyond Alzheimer’s disease, it holds high versatility and strong commercialization potential for the early and rapid in vitro diagnosis and monitoring of various diseases, including cancers, neurological disorders, and infectious diseases.”

This research was supported by the National Research Council of Science & Technology (NST) Research Initiative Program and the Basic Research Program of KRISS. The results were published in April in Biosensors & Bioelectronics (Impact Factor: 10.5), a leading international journal in the field of analytical chemistry.