Summary: In a mouse model of Alzheimer’s disease, regions of the olfactory system with higher amyloid beta accumulation showed reduced activation of olfactory sensory neurons and impaired odor detection.
Source: DGIST
Olfactory dysfunction, including partial loss of smell, is one of the earliest and most common clinical signs of Alzheimer’s disease (AD), affecting roughly 90% of patients. Importantly, most people with AD do not entirely lose their sense of smell; rather, they lose the ability to detect or identify specific odors. This pattern suggests that olfactory impairment in AD may arise from dysfunction localized to particular regions within the olfactory system rather than a global sensory failure.
Amyloid beta (Aβ), a toxic peptide that accumulates in the brains of people with AD, is a key contributor to disease pathology. Aβ is also detectable within the olfactory system, which raises the possibility that regional Aβ deposition could drive localized olfactory deficits. Despite this connection, the precise cellular and regional mechanisms by which Aβ affects olfactory sensory neurons (OSNs) and smell perception have remained unclear.
To clarify these mechanisms, researchers at the Daegu Gyeongbuk Institute of Science and Technology (DGIST), led by Professor Cheil Moon, investigated how Aβ accumulation relates to neuronal activity and odor-guided behavior in an established AD mouse model. Their findings were published in Alzheimer’s Research and Therapy.
The study used a genetically modified mouse line that expresses elevated levels of Aβ and displays neurological features that model aspects of AD. The team evaluated olfactory-driven behaviors, including the ability of mice to locate hidden food items using scent and to distinguish between different odorants. The AD-model mice required significantly more time to find hidden food and demonstrated only partial olfactory function, indicating selective deficits in odor detection and discrimination.
To directly measure neuronal responsiveness, the researchers employed calcium-based sensors to monitor OSN activity in response to odor stimulation. These physiological recordings showed that some odorants elicited normal responses while others did not, mirroring the selective behavioral impairments. Mapping these responses revealed a striking correspondence between areas with high Aβ load and regions showing reduced OSN activation and poor odor detection.
Further anatomical analyses uncovered structural abnormalities and altered cellular turnover in specific parts of the olfactory system, including the olfactory epithelium and the olfactory bulb. The affected regions displayed signs consistent with decreased neuronal proliferation and increased cell death, which would contribute to a diminished population of functional OSNs and therefore to impaired smell perception.
Together, the data indicate that region-specific accumulation of Aβ within the olfactory circuitry can drive localized neuronal dysfunction and structural degradation, producing the selective odor recognition deficits observed in the AD-model mice. These findings link molecular pathology—Aβ deposition—with both physiological impairment of sensory neurons and measurable behavioral consequences in scent-guided tasks.
Professor Moon highlights the potential clinical implications: partial or selective loss of smell could serve as a useful early indicator for identifying individuals at higher risk of developing Alzheimer’s disease. By clarifying how Aβ accumulation disrupts olfactory neurons and which olfactory regions are most vulnerable, the study opens avenues for refining olfactory-based screening methods and for exploring region-targeted strategies to preserve or restore olfactory function. Such approaches might also help reveal therapeutic targets that address early, localized pathology in the olfactory system during AD progression.
About this amyloid beta research news
Source: DGIST
Contact: Kwanghoon Choi – DGIST
Image: The image is in the public domain
Original Research: The research will appear in Alzheimer’s Research and Therapy