A fading sense of smell may be an early warning sign of Alzheimer’s disease. It can appear years before memory loss or cognitive decline.
New research from DZNE and Ludwig-Maximilians-Universität München (LMU), published in Nature Communications, suggests that changes in the brain’s immune system may be to blame. The study is based on both animal and human data. It highlights how immune cells called microglia mistakenly attack nerve fibers. These fibers are crucial for odor perception.
How the Brain Loses Its Sense of Smell
The scientists focused on the link between two brain regions:
- Olfactory bulb – processes signals from the nose’s scent receptors.
- Locus coeruleus – a brainstem region that regulates blood flow, sleep, and sensory processing.
In early Alzheimer’s, nerve fibers connecting these regions appear to malfunction. Microglia interpret them as damaged and begin breaking them down.
The team also found that a fatty acid, phosphatidylserine, shifts to the outside of neuronal membranes in affected fibers. This acts as an “eat-me” signal, prompting microglia to destroy the connections. Researchers believe this shift is triggered by abnormal overactivity of neurons caused by Alzheimer’s-related changes.
What the Evidence Shows
The conclusions are supported by:
- Mouse models with Alzheimer’s features
- Brain tissue from deceased Alzheimer’s patients
- PET scans of living patients with Alzheimer’s or mild cognitive impairment
“These findings show that smell loss in Alzheimer’s is not random—it’s tied to an immunological process that starts very early in the disease,” said Dr. Joachim Herms of DZNE and LMU.
Why This Matters for Early Diagnosis
The results could be especially important as new Alzheimer’s treatments, including amyloid-beta antibody therapies, work best in the early stages of the disease.
“Our findings could pave the way for identifying at-risk patients before memory problems appear,” said Herms. “This would make it possible to begin treatment sooner, when it’s most likely to be effective.”
The Bottom Line
Loss of smell is more than just an inconvenience—it may be an early signal of Alzheimer’s. By uncovering the immune mechanisms behind this symptom, researchers hope to improve both early diagnosis and timely treatment of the disease.