A recent study indicates that a diminishing sense of smell may be an early warning sign of Alzheimer’s disease, potentially appearing before cognitive impairments. Researchers have long sought to identify early indicators of the condition, which could significantly aid in slowing its progression. Previous studies have suggested that changes in speech, breathing, and gut bacteria could signal the onset of Alzheimer’s.
The new research, published in Nature Communications, explored the neural mechanisms behind the loss of smell associated with Alzheimer’s. It involved analyzing positron emission tomography (PET) scans and brain tissue samples from both human patients and mice. The findings suggest that the brain’s immune response plays a critical role in this olfactory decline, with specialized immune cells, known as microglia, damaging the neuronal connections essential for smell perception.
According to Lars Paeger, a neurobiologist affiliated with the German Center for Neurodegenerative Diseases (DZNE) and Ludwig Maximilian University of Munich (LMU), the study revealed that microglia sever connections between the olfactory bulb and the locus coeruleus. The olfactory bulb is a key brain structure responsible for processing scent signals, while the locus coeruleus, located in the brainstem, regulates various physiological functions, including sensory processing related to smell.
“This area of the brain influences the olfactory bulb through long nerve fibers,” Paeger explained. “Changes occurring along these fibers during the early stages of Alzheimer’s disease signal to microglia that the fibers are either defective or unnecessary.” This miscommunication leads to the degradation of crucial connections, ultimately affecting the sense of smell.
The study identified that alterations in the membranes of neurons trigger this process. A fatty acid called phosphatidylserine, typically found within the membrane, relocates to the outer membrane, which serves as a signal for microglia to act. “The presence of phosphatidylserine on the outside of the cell membrane is recognized as an ‘eat-me’ signal for microglia,” Paeger noted. This phenomenon is usually associated with synaptic pruning, a process that removes dysfunctional neuronal connections.
This fatty acid’s movement may be attributed to changes in neuronal behavior due to Alzheimer’s. “We believe that the shift in membrane composition is caused by hyperactivity of neurons affected by Alzheimer’s,” Paeger added. “These neurons exhibit abnormal firing patterns.”
The research employed a comprehensive approach, examining both live and deceased mice displaying Alzheimer’s features, along with post-mortem brain tissue from human patients and PET scans of individuals with Alzheimer’s or mild cognitive impairment. “While olfactory issues and nerve damage in Alzheimer’s have been discussed, the underlying causes were previously unclear,” stated Joachim Herms, another neuroscientist involved in the study. “Our findings point to an immunological mechanism as a cause for these dysfunctions, indicating that these events occur early in the disease.”
Understanding the link between smell loss and Alzheimer’s could enhance early detection efforts, potentially enabling timely interventions. Herms emphasized, “Our findings could pave the way for the early identification of individuals at risk of developing Alzheimer’s, allowing them to undergo thorough testing before cognitive problems manifest. This could facilitate earlier treatment with amyloid-beta antibodies, increasing the chances of a positive response.”
The implications of this research are profound, as early intervention remains critical in managing Alzheimer’s disease effectively. By identifying the relationship between olfactory decline and Alzheimer’s progression, healthcare providers may be better equipped to diagnose and treat patients in the early stages of the condition, ultimately improving outcomes for those affected.
