□ A research team led by Prof. Moon Cheil of the Department of Brain Sciences at the Daegu Gyeongbuk Institute of Science and Technology (DGIST: President Lee Kunwoo), in collaboration with a team led by Prof. Ali Jahanshahi at Maastricht University in the Netherlands, has, for the first time, identified at the cellular level why the olfactory system is the first to be damaged in the early stages of Alzheimer’s disease (dementia).
□ A decline in olfactory function, such as the inability to smell foods or flowers, is considered one of the earliest warning signs of Alzheimer’s disease. This symptom appears long before memory and cognitive function begin to deteriorate significantly, but the specific pathological processes occurring in the brain’s olfactory regions have not been clearly characterized.
□ Alzheimer’s disease is a condition in which toxic proteins, including amyloid beta (Aβ) and tau (pTau), abnormally accumulate in the brain, gradually destroying nerve cells. The academic community has already established that these toxic proteins first accumulate in the olfactory bulb (which initially receives smell signals) and the olfactory cortex (which interprets smell information), rather than in other parts of the brain. However, the response of glial cells (also known as neuroglia), which are responsible for the brain’s immune defense, during this process has remained unclear.
□ To examine this, Prof. Moon’s team conducted a precise analysis of postmortem brain tissue from donors across different cognitive stages, from normal to mild cognitive impairment (a pre-dementia stage) and Alzheimer’s disease. The results revealed that, as the disease progressed, there was a sharp increase in the accumulation of toxic proteins in both the olfactory bulb and the olfactory cortex.
□ In particular, the research team revealed, for the first time, that brain immune cells respond differently depending on the region, even within the same olfactory system. While an immune response led by astrocytes was observed in the olfactory cortex, a distinct response dominated by microglia appeared in the olfactory bulb. This phenomenon can be likened to firefighting: even at the same fire scene, the responding units and strategies vary depending on the building location. If this difference is understood, it will be possible to apply “tailored treatments” to block the progression of Alzheimer’s disease in specific brain regions.
□ The research team also discovered that aggregates of Apolipoprotein E (ApoE) increase consistently in the olfactory systems of all patients, regardless of whether they carry the APOE ε4 gene, which is known to be a strong genetic risk factor for Alzheimer’s disease. This suggests the potential for an early diagnostic marker that can be applied universally to patients with different genetic backgrounds.
□ “This study is a significant achievement that explains at the systems level why the olfactory system is the first and most severely affected by Alzheimer’s disease,” said Prof. Moon. “The different immune cell-pathological networks identified in the olfactory bulb and olfactory cortex will serve as a crucial starting point for developing early diagnostic markers for Alzheimer’s disease and establishing region-specific treatment strategies.”
□ This study was supported by the Ministry of Education, the Ministry of Science and ICT, and the National Research Foundation of Korea through the Priority Research Centers Program and the Mid-Career Researcher Support Program. Notably, this study was led by Jeong Da-hye, a Ph.D. candidate in the Department of Brain Sciences at DGIST, whose capabilities were recognized through her receipt of the “Young Investigator Award” at the IC-KDA & ASAD 2025 (International Conference of the Korean Dementia Association & International Congress of the Asian Society Against Dementia 2025), an international conference on dementia and neurodegenerative diseases held in 2025. Professor Moon Cheil of DGIST and Prof. Ali Jahanshahi of Maastricht University participated as co-corresponding authors. The research findings were published in the April 2026 issue of Alzheimer’s & Dementia , a leading journal in Alzheimer’s disease research.
Alzheimer’s & Dementia
Glial pathology networks reveal early olfactory vulnerability in post mortem human Alzheimer's disease
25-Feb-2026