YOUR NOSE DETECTS ALZHEIMER’S YEARS BEFORE MEMORY LOSS
NEW DELHI: Researchers have uncovered why smell often fades early in Alzheimer’s: the brain’s immune cells dismantle key nerve connections between the olfactory bulb and brainstem. Membrane changes in neurons send an “eat-me” signal to microglia, which mistakenly destroy them. Evidence from mice, human tissue, and PET scans confirms this process. These insights could pave the way for earlier diagnosis and more effective treatment.
A fading sense of smell can be one of the earliest signs of Alzheimer’s disease even before cognitive impairments manifest. Research by scientists at DZNE and Ludwig-Maximilians-Universität München (LMU) sheds new light on this phenomenon, pointing to a significant role for the brain’s immune response, which seems to fatally attack neuronal fibers crucial for the perception of odors. The study, published in the journal Nature Communications, is based on observations in mice and humans, including analysis of brain tissue and so-called PET scanning. These findings may help to devise ways for early diagnosis and, consequently, early treatment.
The researchers come to the conclusion that 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. The olfactory bulb, located in the forebrain, analyzes sensory information from the nose’s scent receptors. The locus coeruleus, a region of the brainstem, influences this processing by means of long nerve fibers originating from neurons in the locus coeruleus and extending all the way to the olfactory bulb. “The locus coeruleus regulates a variety 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,” says Dr. Lars Paeger, a scientist at DZNE and LMU. “Our study suggests that in early Alzheimer’s disease, changes occur in the nerve fibers linking the locus coeruleus to the olfactory bulb. These alterations signal to the microglia that affected fibers are defective or superfluous. Consequently, the microglia break them down.”
Alterations in the membrane
Specifically, the team of Dr. Lars Paeger and Prof. Dr. Jochen Herms, who is a co-author of the current publication, found evidence of changes in the composition of the membranes of the affected nerve fibers: 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,” explains Paeger. “In our situation, we assume that the shift in membrane composition is triggered by hyperactivity of the affected neurons due to Alzheimer’s disease. That is, these neurons exhibit abnormal firing.”
Symbolic picture used
