The brain’s immune cells may explain why a fading sense of smell is an early indicator of Alzheimer’s disease, even before cognitive impairments appear, according to a new study.
Researchers at DZNE and Ludwig-Maximilians-Universität München (LMU) in Germany found that the brain’s immune response seems to fatally attack neuronal fibres critical for the perception of odours.
These olfactory dysfunctions arise because immune cells in the brain, called microglia, remove connections between two regions—the olfactory bulb and the locus coeruleus—the researchers reported in Nature Communications.
The findings, based on observations in mice and humans, including analysis of brain tissue and PET scans, could aid in developing methods for early diagnosis and treatment.
“The locus coeruleus regulates a variety of physiological mechanisms, such as cerebral blood flow, sleep-wake cycles, and sensory processing—including the sense of smell,” said Dr. Lars Paeger, a scientist at DZNE and LMU.
“Our study suggests that in early Alzheimer’s disease, changes occur in the nerve fibres linking the locus coeruleus to the olfactory bulb. These alterations signal to the microglia that the fibres are defective or redundant, leading to their breakdown,” he added.
The team also found changes in the composition of nerve fibre membranes: phosphatidylserine, a fatty acid usually found inside a neuron’s membrane, had shifted to the outside.
“The presence of phosphatidylserine on the outer side of the cell membrane is known to be an ‘eat-me’ signal for microglia. In the olfactory bulb, this is usually part of synaptic pruning, a process that removes unnecessary or dysfunctional neuronal connections,” explained Paeger.
According to the researchers, these insights could pave the way for the early identification of individuals at risk of Alzheimer’s, allowing comprehensive testing and intervention before cognitive decline begins.
—IANS
