Microglia Destroy Smell Nerves in Early Alzheimer's
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- DZNE and Ludwig-Maximilians-Universität München (LMU) scientists published a Nature Communications study showing that microglia destroy nerve fibers connecting the olfactory bulb to the locus coeruleus during early Alzheimer's, years before memory symptoms appear.
- Dr. Lars Paeger and Prof. Dr. Jochen Herms traced the mechanism to phosphatidylserine — a fatty molecule normally on the inside of neuron membranes — shifting to the outer surface and acting as an 'eat-me' signal that prompts microglia to break down the connections.
- The locus coeruleus fibers targeted by this process also regulate cerebral blood flow, sleep-wake cycles, and sensory processing beyond smell, according to Paeger, suggesting the same destructive mechanism could disrupt multiple functions early in disease.
- Evidence was drawn from Alzheimer's-model mice, postmortem human brain tissue, and PET scans from individuals with Alzheimer's or mild cognitive impairment — converging lines of support for the immunological explanation.
- Researchers framed the finding as a path to earlier identification of at-risk patients, enabling intervention with recently available amyloid-beta antibody therapies 'when they must be given early' to be effective.
- The journal reference: Meyer et al., 'Early Locus Coeruleus noradrenergic axon loss drives olfactory dysfunction in Alzheimer's disease,' Nature Communications, 2025; DOI 10.1038/s41467-025-62500-8.
Why it matters: A specific, testable mechanism — phosphatidylserine flipping to the outer membrane and triggering microglial pruning of olfactory nerve fibers — gives clinicians a candidate biomarker window years before cognitive decline. That matters because amyloid-beta antibody therapies, the researchers note, must be given early in the disease process to work, and smell-based screening could be the funnel that gets patients into treatment on time.
