How Your Nose Can Predict Alzheimer’s Disease Years Earlier

As we age, doctors typically keep an eye on vitals like blood pressure and cholesterol levels for cardiovascular concerns. But it can be trickier to spot issues like Alzheimer’s disease before it has already begun to progress. Fortunately, ongoing studies are helping the medical community better understand how to spot the condition before it’s too late. And now, new research says that your nose could help predict Alzheimer’s disease years earlier than ever.

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A change in your sense of smell could be an early sign of Alzheimer’s.

The latest data comes from a study conducted by scientists at the German Center for Neurodegenerative Diseases (DZNE) and Ludwig-Maximilians-Universität München (LMU) that was recently published in the journal Nature Communications.

The researchers began by examining both healthy mice and mice with Alzheimer’s, specifically focusing on the locus coeruleus section of the brainstem (which helps regulate a special kind of neurotransmitter throughout the brain) and how it functioned alongside the olfactory bulb, which handles smell.

The team noted that young mice with Alzheimer’s showed an early degeneration of vital nerve fibers in their locus coeruleus, well before amyloid plaques that typically signify progression of the disease showed up in their brains. This was observed in both imaging performed on the rodent subjects, as well as a decline in smell tests performed on them using food and other odor responses.

The team then carried over the study to humans by examining brain tissue taken from diseased patients who had developed Alzheimer’s, finding that the cadavers showed the same signs of degeneration in their olfactory bulbs. It was again noted in PET scan imaging of living Alzheimer’s patients, whose olfactory bulbs showed signs of inflammation in the same area.

What do these findings mean?

So, what brings about this degeneration? The team says that immune cells known as “microglia” begin to malfunction and remove connections between those two parts of the brain.

“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,” Lars Paeger, PhD, one of the scientists who worked on the study, said in a press release.

“Our study suggests that in early Alzheimer’s disease, changes occur in the nerve fibers linking the locus coeruleus to the olfactory bulb,” he continued. “These alterations signal to the microglia that affected fibers are defective or superfluous. Consequently, the microglia break them down.”

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What caused this degeneration?

The cause for this change remains slightly complicated, but the researchers believe it’s related to the movement of a fatty acid known as phosphatidylserine from the inside of an affected nerve fiber’s membrane to the outside.

“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 is usually associated with a process called synaptic pruning, which serves to remove unnecessary or dysfunctional neuronal connections. 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.”

While the research may not shed light on specific causes, it does help link a longstanding theory that changes in a person’s sense of smell could be used as an early detection tool for cognitive decline.

“Smell issues in Alzheimer’s disease and damage to the associated nerves have been discussed for some time. However, the causes were unclear until yet. Now, our findings point to an immunological mechanism as cause for such dysfunctions—and, in particular, that such events already arise in the early stages of Alzheimer’s disease,” Joachim Herms, PhD, a research group leader at DZNE and LMU and one of the study’s co-authors, said in the press release.

The takeaway:

Researchers in Germany have published study results suggesting that a loss of the sense of smell could be an early sign of Alzheimer’s disease.

Using brain data from mice and both diseased and living patients diagnosed with the condition, the team found that a degeneration of nerve fibers in the area of the brain stem that oversees smell appeared before the amyloid plaque that signifies middle and later phases of progression were spotted.

According to the press release, the early detection capabilities these findings suggest could help doctors begin effective treatment in the typically hard-to-spot early phases of the disease, thanks to newly developed therapies.

“Our 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,” Herms said. “This would allow earlier intervention with amyloid-beta antibodies, increasing the probability of a positive response.”