Toxic Substance Awakens Dementia Brain 'Cleaning Cells'... Amyloid Beta Cleared [Reading Science]

KIST Identifies the 'Reversal Effect' of Low-Dose Quinolinic Acid
Improved Memory in Mice with Dementia... Potential for New Treatment Strategies

A new finding has revealed that a brain metabolite, previously known for damaging neurons, can actually activate the brain's ‘cleaning cells’ and help remove Alzheimer’s-causing proteins when present at low concentrations. When applied to mice with dementia, the accumulated amyloid beta in their brains decreased and their memory functions improved.

The Korea Institute of Science and Technology (KIST) announced on September 15, 2026, that a research team led by Senior Researcher Ryu Hoon from the Brain Disease Research Group and Senior Researcher Lee Hyunbeom from the Biomolecular Recognition Research Center, in collaboration with Professor Lee Jeonghee’s team at Boston University School of Medicine in the United States, has identified a new mechanism that enhances the waste clearance ability of microglia, which are immune cells in the brain.

The process by which quinolinic acid activates the 'brain cleaning function' of microglia. When low concentrations of quinolinic acid (QA) activate phospholipid synthesis and the GABARAP protein, microglia more effectively remove amyloid beta (Aβ), reducing brain plaques and aiding cognitive function recovery. Provided by the research team

Alzheimer’s disease is a degenerative brain disorder in which abnormal proteins such as amyloid beta accumulate in the brain and damage neurons. Although the brain contains microglia that capture and remove such waste, their cleaning function declines as aging or disease progresses.

The research team focused on ‘quinolinic acid (QA)’, a brain metabolite. While quinolinic acid is known to be neurotoxic at high concentrations, the study found that at low concentrations, it actually enhances microglia’s waste removal capability.

The 'Reversal' of a Toxic Substance: Enhancing Brain Immune Cell Cleaning Ability

When microglia are stimulated with low levels of quinolinic acid, a key enzyme in the pathway that synthesizes phospholipids—the fatty components of the cell membrane—was activated. The ‘PE phospholipid’ produced in this process made the cell membrane more flexible and bonded with ‘GABARAP’, a protein involved in autophagy. Through this mechanism, microglia were able to more effectively capture and break down toxic proteins in the brain.

This is an example of the so-called ‘hormesis’ phenomenon, where low amounts of harmful substances or stress boost the organism’s defense capabilities. The researchers named this newly discovered waste clearance pathway “GAP (GABARAP-Associated Phagocytosis).”

Changes in microglia observed in the brains of patients with Alzheimer's disease. Analysis of postmortem brain tissue revealed a significant increase in the GABARAP protein, which is involved in waste removal, in the microglia of Alzheimer's disease patients compared to normal individuals. Provided by the research team.

The effect was also observed in animal experiments. When the researchers locally administered low-dose quinolinic acid to the brains of Alzheimer’s model mice, amyloid beta plaques in the hippocampus—responsible for memory—were significantly reduced within a few days. Damaged neuronal connections were restored, and both short-term and long-term memory capabilities improved to normal mouse levels.

According to the research team, rather than directly using quinolinic acid as a dementia treatment, this study may support the development of a therapy that selectively activates the “cleaning system” of microglia triggered by quinolinic acid. There is also the possibility of expanding this research to other neurodegenerative diseases characterized by abnormal protein accumulation, such as Parkinson's or Huntington’s disease.

Senior Researcher Ryu stated, “We revealed that a metabolite, once regarded only as a dementia-promoting substance, can act as a signal to boost resilience in brain immune cells at low concentrations. This is meaningful in that we have proposed a new strategy for dementia treatment based on the metabolism and cleaning functions of brain immune cells.”

Senior Researcher Lee added, “We plan to identify new therapeutic candidates that selectively activate the cleaning system of microglia, and work with pharmaceutical and biotech companies to conduct preclinical validation and promote technology transfer.”

The research results were published in the international journal ‘Signal Transduction and Targeted Therapy’.

This content was produced with the assistance of AI translation services.