Link Between Brain Immune Response and Olfactory Dysfunction in Alzheimer's Disease

Recent research sheds light on the early signs of Alzheimer's disease, particularly the loss of the sense of smell, which often appears before cognitive impairments. Scientists from DZNE and Ludwig-Maximilians-Universität München (LMU) have identified a significant role of the brain's immune system in this process, revealing that it may attack neuronal fibers essential for odor perception.

The study, published in Nature Communications, utilized observations from both mice and humans, including brain tissue analysis and PET scans. The findings suggest that immune cells known as microglia contribute to olfactory dysfunction by removing connections between the olfactory bulb and the locus coeruleus, a brainstem region that influences sensory processing.

The olfactory bulb, situated in the forebrain, processes scent signals received from sensory receptors, while the locus coeruleus modulates this process through nerve fibers extending to the olfactory bulb. Dr. Lars Paeger from DZNE explains that the locus coeruleus also regulates vital functions such as blood flow and sleep cycles, and it plays a crucial role in sensory perception, including smell.

The research indicates that in early Alzheimer's, changes in nerve fibers linking these two regions prompt microglia to identify these fibers as defective or unnecessary, leading to their breakdown. A key discovery is the alteration in the membrane composition of affected nerve fibers, notably the externalization of phosphatidylserine, a fatty acid that signals microglia to initiate removal. This abnormal membrane shift is thought to result from hyperactivity of neurons affected by Alzheimer's.

The comprehensive findings, based on animal models, human brain samples, and imaging studies, reveal an immunological mechanism behind early olfactory deficits in Alzheimer's. This insight opens new avenues for early diagnosis, allowing for interventions such as amyloid-beta antibody treatments at stages when the disease is still manageable. Detecting odor loss and understanding its immunological basis could enable earlier intervention, potentially improving outcomes for at-risk individuals.

Source: https://medicalxpress.com/news/2025-08-brain-immune-response-linked-olfactory.html