Researchers from the German Center for Neurodegenerative Diseases (DZNE) and Ludwig Maximilian University in Munich focused on a brain area known as the ‘locus coeruleus’ (LC). This small, under-researched region plays a crucial role in regulating functions such as cerebral blood flow, sleep-wake cycles, and sensory processing, according to ‘New Atlas’.
Using a mouse model that simulates the early stages of Alzheimer’s disease, the researchers discovered that nerve fibers in the locus coeruleus, which connect it to the olfactory bulb, began to deteriorate early on, even before symptoms like memory loss appeared. Utilizing an advanced 3D imaging technique known as ‘iDISCO+’, the researchers observed that these fibers exhibited abnormal expression of ‘phosphatidylserine’ on their surfaces.
Behavioral tests conducted on the mice confirmed their impaired ability to detect and distinguish between odors due to this deterioration. In the context of human studies, analysis of brain tissues from deceased Alzheimer’s patients showed similar signs of nerve fiber degeneration in the locus coeruleus, along with the activity of microglial cells.
Moreover, PET scans of individuals in the early stages of the disease revealed similar disruptions in the locus coeruleus and olfactory bulb pathway. This hyperactivity leads to abnormal signals that make the nerve fibers appear defective, prompting microglial cells to remove them in a process known as ‘synaptic pruning’.
These findings open promising avenues for developing early diagnostic tools based on smell tests, as well as preventative treatments targeting immune dysfunction in the early stages of the disease. Dr. Joachim Herms, the lead researcher, emphasizes that these discoveries could pave the way for early detection of individuals at risk of Alzheimer’s, enabling more effective therapeutic interventions, such as the use of amyloid-beta antibodies, before neurological damage becomes severe.
