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, namely the olfactory bulb and the locus coeruleus, they noted in the paper published in the journal Nature Communications.
These findings, based on observations in mice and humans, including analysis of brain tissue and so-called PET scanning, may help to devise ways for early diagnosis and, consequently, early treatment.
“The locus coeruleus regulates a variety of physiological mechanisms. These include, for example, cerebral blood flow, sleep-wake cycles, and sensory processing. The latter applies, in particular, also to 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 affected fibres are defective or superfluous. Consequently, the microglia break them down,” Paeger added.
Specifically, the team found evidence of changes in the composition of the membranes of the affected nerve fibres: Phosphatidylserine, a fatty acid that usually occurs inside a neuron’s membrane, had been moved to the outside.
“Presence of phosphatidylserine at the outer site of the cell membrane is known to be an ‘eat-me’ signal for microglia. In the olfactory bulb, this is usually associated with a process called synaptic pruning, which serves to remove unnecessary or dysfunctional neuronal connections,” explained Paeger.
The findings could pave the way for the early identification of patients at risk of developing Alzheimer’s, enabling them to undergo comprehensive testing to confirm the diagnosis before cognitive problems arise.