A fading sense of smell may be one of the first warning signs of Alzheimer’s disease, even before memory problems appear.
New research from scientists at DZNE and Ludwig-Maximilians-Universität München (LMU) in Germany has uncovered how the brain’s own immune system could be causing this early symptom.
The findings were published in the journal Nature Communications and are based on studies in both mice and humans. This discovery may help doctors find the disease earlier and start treatments sooner.
The researchers found that a specific part of the brain, called the olfactory bulb, which helps us detect smells, becomes disconnected from another brain area called the locus coeruleus.
The locus coeruleus controls many brain functions, including blood flow, sleep, and sensory experiences such as smell. It sends long nerve fibers to the olfactory bulb to help process odors. In early Alzheimer’s, these nerve fibers are attacked by the brain’s immune cells, called microglia.
Dr. Lars Paeger, one of the lead scientists, explains that these fibers show changes that trick microglia into thinking they are damaged and need to be destroyed. A substance called phosphatidylserine, normally found inside the nerve cells, moves to the outer surface of the cell.
This acts like a signal that says “eat me” to the microglia. This process is usually helpful in removing old or broken connections, but in this case, it’s removing working nerve fibers too early.
The researchers believe this harmful process is caused by the neurons becoming too active, a common feature in early Alzheimer’s. This abnormal activity may trigger the shift in the nerve cells’ membrane, leading to unnecessary pruning by microglia.
The team’s conclusions are based on many types of evidence. They studied genetically modified mice that mimic Alzheimer’s disease, examined brain tissue from people who had Alzheimer’s, and used brain scans (called PET scans) on living patients with Alzheimer’s or mild cognitive impairment. All of these methods supported their findings.
Professor Joachim Herms, another senior researcher on the project, says that although problems with smell in Alzheimer’s have been known for some time, this study is the first to clearly point to the brain’s immune response as a cause. He believes this could change how doctors think about early warning signs of the disease.
This research could also help with earlier diagnosis. New treatments for Alzheimer’s using amyloid-beta antibodies work best in the early stages of the disease.
If doctors can identify smell problems and connect them to these early brain changes, patients could get tested and treated before memory loss begins. This might improve their chances of responding to treatment.
This study offers a new window into the earliest changes in Alzheimer’s disease, and how the brain’s own defenses may be involved in harming important connections long before symptoms of memory loss begin.
If you care about Alzheimer’s, please read studies about Scientists find the root cause of Alzheimer’s disease and findings of Alzheimer’s might not be primarily a brain disease. A new theory suggests it’s an autoimmune condition.
For more about Alzheimer’s disease, please read studies about These places in U.S. have the most cases of Alzheimer’s disease and findings of Scientists confirm the link between COVID-19 and Alzheimer’s disease.
The study is published in Nature Communications.
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