ScienceAlert reports on a brain-scan study that finds the loss of smell — apparently triggered by a misfiring immune response in the brain — may give patients an earlier warning of Alzheimer’s disease than problems with speech and memory:
In the new research, scientists sought to uncover the neural underpinnings of the disease, analyzing positron emission tomography (PET) scans and brain tissue samples from mice as well as humans.
Their findings suggest the brain’s immune response plays a key role in the loss of smell linked to Alzheimer’s, seemingly killing off neuronal fibers the brain needs for odor perception.
Specialized immune cells in the brain known as microglia sever connections between the olfactory bulb and the locus coeruleus, the study found.
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The locus coeruleus is in the brainstem, but it influences the olfactory bulb and other brain areas via long nerve fibers, explains neurobiologist Lars Paeger from the German Center for Neurodegenerative Diseases (DZNE) and Ludwig Maximilian University of Munich (LMU).
“The locus coeruleus regulates a variety of physiological mechanisms. These include, for example, cerebral blood flow, sleep-wake cycles, and sensory processing,” he says. “The latter applies, in particular, also to the sense of smell.”
In early stages of Alzheimer’s disease, pivotal changes occur along those nerve fibers linking the locus coeruleus to the olfactory bulb, the new study suggests.
“These alterations signal to the microglia that affected fibers are defective or superfluous,” Paeger says. “Consequently, the microglia break them down.”
The changes occur in the membranes of neurons, where a fatty acid known as phosphatidylserine – typically located inside the membrane – has moved to the exterior. That’s likely what drew attacks by microglia.
“Presence of phosphatidylserine at the outer site of the cell membrane is known to be an ‘eat-me’ signal for microglia,” Paeger says. “In the olfactory bulb, this is usually associated with a process called synaptic pruning, which serves to remove unnecessary or dysfunctional neuronal connections.”
This fatty acid’s relocation may occur because Alzheimer’s disease is already causing the nerve cells to behave differently.
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You can read more of the smell study here, in Nature Communications.