New Delhi: Brain’s immune cells may explain why a fading sense of smell is an early signal for Alzheimer’s disease even before cognitive impairments manifest, according to a study.
Researchers at DZNE and Ludwig-Maximilians-Universität München (LMU) in Germany revealed that the brain’s immune response seems to fatally attack neuronal fibres crucial for the perception of odours.
These olfactory dysfunctions arise because immune cells of the brain, called microglia, remove connections between two brain regions — the olfactory bulb and the locus coeruleus, they noted in the paper published in Nature Communications.
Observations in Mice and Humans
The findings, based on observations in mice and humans, including analysis of brain tissue and PET scans, may help in devising methods for early diagnosis and treatment.
“The locus coeruleus regulates a variety of physiological mechanisms such as blood flow, sleep-wake cycles, and sensory processing, particularly the sense of smell,” said Dr. Lars Paeger, scientist at DZNE and LMU.
How Microglia Target Nerve Fibres
The study suggests that in early Alzheimer’s disease, nerve fibres linking the locus coeruleus to the olfactory bulb undergo changes. These alterations mark the fibres as defective, prompting microglia to break them down.
The researchers detected a shift in the composition of nerve cell membranes: phosphatidylserine, usually inside a neuron’s membrane, had moved to the outside.
‘Eat-Me’ Signal for Microglia
“Presence of phosphatidylserine at the outer site of the cell membrane is known to be an ‘eat-me’ signal for microglia,” Paeger explained. In the olfactory bulb, this process — usually part of synaptic pruning — helps remove unnecessary or dysfunctional connections, but in Alzheimer’s it may trigger premature loss of vital nerve fibres.
Potential for Early Diagnosis
The findings could pave the way for identifying patients at risk of Alzheimer’s much earlier, allowing them to undergo comprehensive testing and interventions before cognitive problems arise.