Does Loss of Smell Reveal the Early Signs of Alzheimer’s Disease?
A simple biopsy of nasal cells could help detect the very earliest stages of Alzheimer’s disease, long before cognitive symptoms appear. Researchers analyzed samples taken from the olfactory mucosa of individuals at different stages of the disease, including healthy people with biological markers indicating future risk. Their findings show that this easily accessible region reflects inflammatory and neuronal changes characteristic of the disease, paving the way for early and non-invasive diagnosis.
The olfactory mucosa, located in the upper part of the nose, contains sensory neurons directly connected to the brain. In people with Alzheimer’s disease, these neurons accumulate abnormal proteins similar to those observed in affected brain regions. Using advanced cellular analysis techniques, scientists identified early signs of inflammation and neuronal stress in this mucosa, even in individuals with no apparent cognitive impairment but carrying biological markers of the disease.
The study involved three groups: healthy adults, individuals with Alzheimer’s disease and cognitive symptoms, and adults without symptoms but with abnormalities in their cerebrospinal fluid, indicating a preclinical stage. The results reveal abnormal activation of certain immune cells, particularly T lymphocytes, as well as increased inflammatory programs in microglia-like cells. These changes, observed as early as the preclinical stage, intensify as the disease progresses.
Olfactory neurons, responsible for detecting odors, also show molecular alterations. For example, the expression of genes linked to inflammation and oxidative stress is increased, while the expression of protective genes is reduced. These changes suggest disrupted communication between neurons and immune cells, a mechanism that may contribute to neuronal degeneration.
Analysis of nasal samples thus allows tracking of disease progression and identification of potential targets for treatments. This approach provides a practical way to study the early mechanisms of Alzheimer’s disease, which are often difficult to observe in the living brain. It could also complement current tests, such as blood analyses or imaging exams, to refine diagnosis and patient monitoring.
In summary, the olfactory mucosa acts as a window into the brain, revealing pathological processes long before symptoms appear. This discovery could transform the management of the disease by enabling earlier and more targeted intervention.
Attributions and Sources
Origin of the Study
DOI: https://doi.org/10.1038/s41467-026-70099-7
Title: Olfactory cleft biopsy analysis of Alzheimer’s disease pathobiology across disease stages
Journal: Nature Communications
Publisher: Springer Science and Business Media LLC
Authors: Vincent M. D’Anniballe; Sarah Kim; John B. Finlay; Michael Wang; Tiffany Ko; Sheng Luo; Heather E. Whitson; Kim G. Johnson; Bradley J. Goldstein