A new study by scientists at DZNE and Ludwig-Maximilians-Universität München (LMU) has revealed that a declining sense of smell could be one of the earliest warning signs of Alzheimer’s disease, long before memory problems begin.
The research suggests that the brain’s immune system plays a key role in this process, mistakenly targeting and damaging nerve fibers that are essential for detecting odors.
Published in the journal Nature Communications, the study examined both mice and human brain tissue, and also included brain imaging scans.
The findings may help doctors detect Alzheimer’s sooner and start treatment earlier, when it could be more effective.
The researchers discovered that immune cells in the brain called “microglia” remove connections between two important brain regions: the olfactory bulb, which processes smells, and the locus coeruleus, which plays a role in many brain functions, including how we experience smells.
The nerve fibers linking these two areas are damaged in the early stages of Alzheimer’s, and microglia mistakenly treat them as broken or unnecessary, breaking them down in a process known as synaptic pruning.
Dr. Lars Paeger, one of the study’s authors, explained that the problem seems to begin when nerve cells become hyperactive due to Alzheimer’s disease. This abnormal activity causes changes in the outer membrane of the nerve fibers.
A fatty molecule called phosphatidylserine, which is normally hidden inside the cell membrane, moves to the outside. This molecule acts like a signal for microglia to “eat” the nerve fibers, leading to damage in the olfactory system.
This immune response, while normally used by the brain to clean up damaged or unnecessary cells, becomes harmful in this case. It leads to the destruction of healthy neural connections that help transmit smells from the nose to the brain.
To support their findings, the researchers used a wide range of data. They studied genetically modified mice that mimic Alzheimer’s, examined brain samples from deceased Alzheimer’s patients, and conducted PET scans on people with either Alzheimer’s or mild cognitive issues.
All this evidence pointed to the same conclusion: damage to the brain’s smell pathways begins early in the disease and is caused by the brain’s own immune response.
According to Prof. Jochen Herms, another senior author of the study, this discovery could help improve early diagnosis of Alzheimer’s. Recently developed treatments using amyloid-beta antibodies are believed to work best when used early in the disease.
Detecting changes in the sense of smell may offer a new, non-invasive way to flag individuals who are at higher risk.
By identifying these patients early, doctors could carry out further tests to confirm Alzheimer’s before memory loss begins. This could open the door to earlier treatment and a better chance of slowing the disease’s progression.
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The study is published in Nature Communications.
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