People with Alzheimer’s may notice a weaker sense of smell before they forget things. Researchers from DZNE and LMU discovered why this happens. Their work, published in Nature Communications, used mouse experiments, human brain tissue, and PET scans to explain the link.
The problem starts when tiny immune cells in the brain, called microglia, begin to cut off connections between two key areas: the olfactory bulb (which receives scent signals) and the locus coeruleus (which helps control those signals). The locus coeruleus sends long nerve fibers to the olfactory bulb.
Dr. Lars Paeger explains, “The locus coeruleus helps control blood flow, sleep, and how we sense the world, including smell. In early Alzheimer’s, the nerve fibers between these two regions become damaged. Microglia see the damaged fibers as unwanted and remove them.”
Cell‑membrane warning signal
When a cell’s outer membrane shows a molecule called phosphatidylserine, microglia treat it as an “eat‑me” flag. Normally this helps the brain prune away unused connections. In Alzheimer’s, over‑active neurons may expose this flag, causing microglia to destroy the scent‑carrying fibers.
Proof from mice, human tissue, and scans
The scientists saw the same pattern in mouse models, in brain samples from people who had died, and in PET scans of patients with Alzheimer’s or mild cognitive problems.
Joachim Herms adds, “People have known that smell loss happens in Alzheimer’s, but we did not know why. Our results point to an immune‑driven attack that starts early in the disease.”
What this means for early detection
New medicines that target amyloid‑beta work best when given early. If doctors can spot smell loss and the related brain changes, they could test patients before memory issues appear and start treatment sooner.
Herms says, “With our findings, doctors might identify at‑risk people early, run detailed tests, and begin amyloid‑beta therapy while it still has a good chance to help.”