[Alzheimer's represented as a puzzle. Photo Credit: Pixabay]

New research published in the journal Nature Communications in April has found that a deteriorating sense of smell may be one of the first indicators of Alzheimer's disease, manifesting even before obvious memory issues.

The study, conducted by researchers at DZNE and Ludwig-Maximilians-Universität für (LMU), sheds new light on the role of the immune system in the brain, suggesting it may unintentionally target nerve fibers essential for smell detection. 

The study integrated data from both humans and mice, such as brain tissue analysis and PET scanning. 

These findings may facilitate earlier treatment and enhance early detection. 

The researchers theorize that smell-related issues arise when immune cells in the brain called microglia start severing connections between two crucial areas: the locus coeruleus and the olfactory bulb. 

The forebrain's olfactory bulb interprets messages from the nose's scent receptors. 

Through lengthy nerve fibers that reach the olfactory bulb, the brainstem's locus coeruleus aids in controlling this process. 

The locus coeruleus regulates various physiological processes, including cerebral blood flow, sleep-wake cycles, and sensory processing. 

The latter, in particular, relates to the sense of smell, and the research indicates that alterations take place in the nerve fibers that connect the locus coeruleus to the olfactory bulb in the early stages of Alzheimer's disease. 

These changes signal to the microglia that the impacted fibers are faulty or unnecessary and as a result, the microglia degrade them. 

Under the direction of Dr. Lars Paeger and co-author Dr. Jochen Herms, the team uncovered particular alterations in these nerve fibers' membranes. 

They found that the fatty molecule phosphatidylserine, typically situated on the inside of a neuron's membrane, had moved to the outside. 

Microglia are known to get an "eat-me" signal when phosphatidylserine is present at the outer site of the cell membrane and in the olfactory bulb, this is typically associated with a process called synaptic pruning, which serves to remove unnecessary or dysfunctional neuronal connections. 

In this study, the researchers hypothesized that the shift in membrane composition is triggered by hyperactivity of the affected neurons due to Alzheimer's disease; in other words, these neurons fire abnormally. 

The researchers examined brain tissue from deceased patients, reviewed positron emission tomography (PET) scans from people with Alzheimer's or moderate cognitive impairment, and studied mice with Alzheimer's-like characteristics.

Alzheimer's disease-related smell problems and nerve damage have long been discussed, but up until now, the cause remained unknown. 

Current research suggests that these dysfunctions are caused by an immune mechanism, and that these dysfunctions are already present in the early stages of Alzheimer's disease. 

Alzheimer's disease can now be treated with so-called amyloid-beta antibodies and these treatments must be administered early in the course of the illness in order for them to be successful. 

This is where the new research may have a significant impact as the research may help identify people who are at risk for Alzheimer's disease early on, allowing them to have thorough testing to confirm the diagnosis before cognitive issues occur. 

This could increase the likelihood of a good response by enabling earlier amyloid-beta antibody intervention.