The Nose May Reveal Alzheimer's Before Memory Fails

The study investigated the use of nasal tissue as an accessible way to detect early changes in Alzheimer's disease. By analyzing cells collected from different groups of individuals, researchers identified signs of inflammation and neuronal damage even in the early stages of the disease. These findings suggest that the olfactory epithelium may be a promising tool for early diagnosis and the development of new treatment strategies.

Alzheimer's disease is a condition that progressively affects the brain, impairing memory, thinking, and behavior. A curious and increasingly studied aspect of this disease is the loss of smell, known as anosmia, which can appear even before the classic memory symptoms.

This has sparked the interest of scientists, as it suggests that changes in the olfactory system may be one of the first signs of the disease, offering a valuable opportunity for early diagnosis.

The system responsible for smell begins in a region located in the upper part of the nose, called the olfactory epithelium. This area contains specialized cells that capture odors and send signals directly to the brain.

These connections reach brain regions important for memory, such as the entorhinal cortex, which is one of the first areas affected in Alzheimer's disease. This helps explain why changes in the sense of smell may be so closely linked to the onset of the disease.

Previous studies have shown that these nasal cells can exhibit changes similar to those found in the brains of people with Alzheimer's disease, such as the accumulation of abnormal proteins associated with the disease.

Furthermore, there is a physical connection between the brain and the nasal cavity through which nervous system fluids circulate, making this region even more interesting for investigation. Because it is easily accessible, the olfactory epithelium can act as a "window" to observe what is happening in the brain without the need for invasive procedures.

Despite these findings, most previous research has been conducted with tissues from people in advanced stages of the disease or after death, which limits the understanding of initial events.

With recent technological advances, it has become possible to collect samples of the olfactory epithelium simply, during medical consultations, using minimally invasive techniques. In addition, new tools allow for the analysis of these samples at a very detailed level, observing the behavior of individual cells.

Researchers Bradley J. Goldstein, M.D., Ph.D. and Vincent M. D’Anniballe Credit: Duke Health/ Shawn Rocco.

In this study, researchers collected nasal samples from three different groups of people: healthy individuals with normal cognitive function, people with clear signs of Alzheimer's confirmed by biological tests, and individuals who did not yet have symptoms but already had alterations in biological markers indicating a high risk of developing the disease. This comparison allowed them to investigate changes that occur from the earliest stages to the most advanced phases.

The analysis of the samples was done using an advanced technique that allows them to study which genes are active in each cell individually. This made it possible to identify different types of cells present in the tissue and observe how they were behaving.

The researchers focused especially on immune system cells and neurons responsible for smell. They also used another method to confirm the activation of specific defense cells, analyzing how they responded in each group studied.

Example of a nasal swab sample Credit: Duke Health/Shawn Rocco

The results showed that inflammatory changes and signs of cellular damage were already present even in people without obvious symptoms, but with a high risk of Alzheimer's. In particular, an increase in the activity of certain immune system cells was observed, which appear to contribute to inflammation and possible damage to olfactory neurons.

These changes were similar to those found in more advanced stages of the disease, indicating that the process begins long before the appearance of classic symptoms.

READ MORE:

Olfactory cleft biopsy analysis of Alzheimer’s disease pathobiology across disease stages

Vincent M. D’Anniballe, Sarah Kim, John B. Finlay, Michael Wang, Tiffany Ko, Sheng Luo, Heather E. Whitson, Kim G. Johnson, and Bradley J. Goldstein

Nature Communications. 18 March 2026. 17, Article number: 2245 (2026)

DOI: 10.1038/s41467-026-70099-7

Abstract:

Alzheimer’s Disease (AD) is a neurodegenerative condition affecting millions worldwide. Defining early pathobiological events remains challenging, in part due to inaccessibility of neural tissue. Because olfactory neurons are accessible, and olfactory loss is prevalent in AD, we evaluated olfactory brush biopsies from controls, individuals with cerebrospinal fluid (CSF) biomarker-confirmed AD, and cognitively typical individuals whose positive CSF biomarkers signal a pre-clinical AD stage. Here we show via single cell RNA-sequencing (n = 22 subjects) conserved neuroinflammatory T cell, myeloid cell, and olfactory neuron changes detectable even in pre-clinical AD subjects, and corroborate heightened CD8 T-cell activation by flow cytometry. Activated memory T cell states in the olfactory epithelium were a hallmark of pre-clinical AD, paralleling CSF T cell phenotypes seen in advanced disease, accompanied by both microglia-like inflammatory programs and evidence of olfactory neuron inflammatory injury. Together, our findings establish a platform permitting analysis of neural tissue in AD at its earliest stages.