KAIST team develops neural chip to track Alzheimer's drug response

What happens in the brain after an Alzheimer's drug is administered? A joint research team led by KAIST has used a small, implantable neural chip to wirelessly monitor real-time changes in a neurotransmitter involved in memory and learning. In miniature pigs (minipigs), the team observed an increase in the neurotransmitter signal following drug administration, followed by a gradual return to baseline. The technology could help researchers assess how drugs act in the brain and develop stimulation methods that adapt to the brain's response.

KAIST (President Choongsik Bae) announced on October 27 that a research team led by Professor Kyung-In Jang from the Department of Mechanical Engineering, in collaboration with researchers from the Daegu Gyeongbuk Institute of Science and Technology (DGIST), the Korea Brain Research Institute (KBRI), and the Korea Research Institute of Bioscience and Biotechnology (KRIBB), has developed an implantable neural chip that integrates a sensor for detecting the neurotransmitter acetylcholine, a light-stimulation component, and miniaturized wireless measurement technology.

Acetylcholine transmits signals between nerve cells and plays an important role in memory and learning. Donepezil, a drug used to treat Alzheimer's disease, inhibits acetylcholinesterase, the enzyme that breaks down acetylcholine, allowing the neurotransmitter to remain active for longer periods of time. Tracking changes in acetylcholine in specific brain regions after drug administration can help researchers better understand the drug's action.

The research team implanted the neural chip in the prefrontal cortex of minipigs, administered donepezil, and wirelessly measured acetylcholine signals. The prefrontal cortex is involved in cognitive functions such as judgment, attention, and memory. Following drug administration, the acetylcholine signal increased and then gradually returned to baseline. The findings demonstrate that chemical responses in a specific brain region can be continuously monitored using an external device.

At the heart of the sensing technology is a layer that converts changes in neurotransmitter levels into electrical signals. The researchers combined porous chitosan with ultrathin silver-platinum (Ag@Pt) nanowires. The porous structure provides a large surface area for attaching the enzymes used to detect acetylcholine. The nanowires convert hydrogen peroxide produced by the enzymatic reaction into electrical signals.

The team also designed the chip to minimize interference from other molecules. The researchers placed an enzyme-coated electrode on one side of the thin probe inserted into the brain and an electrode without enzymes on the other. By comparing the two signals, the system reduces interference detected by both electrodes and isolates changes associated with acetylcholine. The measurements are processed by a miniaturized circuit and transmitted to an external device via Bluetooth.

In addition to sensing changes in the brain, the neural chip can stimulate nerve cells with light. In a separate experiment involving transgenic mice, the team confirmed that acetylcholine signals increased in response to light stimulation delivered by a micro-light-emitting diode (μLED) integrated into the chip.

The animal experiments drew on the expertise of the partner institutions. KRIBB provided the minipigs and support for surgical procedures, while KBRI supported mouse surgeries and experiments.

The technology could help researchers investigate how drugs for brain diseases act in the brain. In particular, it could enable comparisons of neurotransmitter responses across different drug doses and dosing intervals.

The study also lays the groundwork for research into closed-loop neural interfaces, which adjust stimulation based on ongoing measurements of the brain's response. In such systems, a sensor detects changes following stimulation, and the intensity or timing of subsequent stimulation is adjusted accordingly. By integrating sensing and light stimulation into a single chip, the study provides a foundation for developing these systems.

However, the study measured neurotransmitter changes in animal brains and did not demonstrate therapeutic effects on Alzheimer's disease or improvements in memory. Further validation is needed before the technology can be used in humans, including assessments of its long-term safety and the stability of its measurement performance after implantation.

This study lays the groundwork for technologies that monitor changes in the brain and adjust stimulation based on its response."

Professor Kyung-In Jang, Department of Mechanical Engineering, KAIST

He added that the technology could help researchers investigate how drugs act in the brain and identify stimulation methods tailored to the brain's condition.

The research team plans to commercialize the technology through N-Side Inc. (CEO Kyung-In Jang), a faculty-founded startup.

Jieun Son, Saehyuck Oh, and Jeongdae Ha from DGIST contributed as co-first authors, and Professor Jang served as the corresponding author. The findings were published on October 14 in Device, a Cell Press journal covering devices and applied technologies.