Researchers discover the “Eat-me” signal which triggers the first symptom of Alzheimer’s

Damage to nerve fibers to immunity can underline the loss of early smell in Alzheimer’sOffering a new path for early diagnosis.

A decrease in smell may appear as one of the first indicators of Alzheimer’s disease, often emerging before the notable cognitive decline. Researchers from Dzne and Ludwig-Maximiliens-Universität München (LMU) have revealed new perspectives on this process, identifying a major role for the immune response of the brain.

Their results suggest that target immune activity and wrongly destroy the nerve fibers essential to the perception of odors. The study, reported in Nature communicationsBases on mouse and humans data, including brain tissue analyzes and PET imaging. This knowledge could support previous diagnosis and intervention.

The team concluded that these odor -related deficiencies occur when microglia, resident brain immune cells, strip connections between two key regions: the olfactory bulb and the locus coeruleus. The olfactory bulb, located in the anterior brain, processes the signals of the perfume receptors of the nose. The Locus Coeruleus, which is part of the brainstem, influences this treatment through long nerve fibers which extend in the olfactory bulb.

“Locus coeruleus regulates a variety of physiological mechanisms. These include, for example, brain blood flow, sleepy sleep cycles and sensory treatment. The latter applies, in particular, also in the sense of smell, “explains Dr. Lars Paeger by Dzne and LMU.

“Our study suggests that in early Alzheimer’s disease, changes occur in nerve fibers connecting locus coeruleus to the olfactory bulb. These alterations point out to microglia which affects the fibers is defective or superfluous. Therefore, microglia breaks them down. “

Membrane changes

Dr. Lars Paeger and Professor Dr. Jochen Herms, co-author of the study, found clear evidence of a composition of the altered membrane in affected nerve fibers. They observed that phosphatidylserin, a fat acid Normally located on the inside of the membrane of a neuron, had moved to the outer surface.

“The presence of phosphatidylserin at the external site of the cell membrane is known to be an” EAT-ME “signal for microglia. In the olfactory bulb, this is generally associated with a process called synaptic pruning, which is used to eliminate unnecessary or dysfunctional neural connections, ”explains Paeger.

“In our situation, we assume that the discrepancy of the composition of the membrane is triggered by the hyperactivity of affected neurons due to Alzheimer’s disease. That is to say that these neurons have an abnormal shot. ”

A wide range of data

The results of Paeger and colleagues are based on a plethora of observations. These include studies on mice with characteristics of Alzheimer’s disease, analysis of brain samples of deceased Alzheimer’s patients and post-emission tomography (TEP) of the brains of people with Alzheimer’s or light cognitive impairment.

“Odor problems in Alzheimer’s disease and associated nerve damage has been discussed for some time. However, the causes were not clear so far. Now our results indicate an immunological mechanism as a cause of such dysfunctions – and, in particular, that such events already occur in the early stages of Alzheimer’s disease, “explains Joachim Herms, a research group on Dzne and LMU”. “Synergy” cluster based in Munich.

Early diagnostic perspectives

The so-called amyloid-bêta antibodies have recently become available for the treatment of Alzheimer’s. For this new therapy to be effective, it must be applied to an early stage of the disease, and it is precisely where current research could be significant.

“Our results could open the way to early identification of patients at risk of developing Alzheimer’s disease, allowing them to undergo complete tests to confirm the diagnosis before cognitive problems arise.

Reference: “Locus Early Locus Coeruleus Noradrenergic The axonal loss leads to Alzheimer’s disease” by Carolin Meyer, Theresa Niedermeier, Paul Lc Feyen, Felix L. Strüing Svenja-Lotta Rumpf, Katharina Ochs, Karin Wind-Mark, Gloria Biechele, Jessica Wagner, Selim Guersel, Carolin I. Kurz, Meike Schweiger, Danilo Prtvar, Yuan Shi Perneczky, Thomas Koeglsperger, Jonas J. Neher, Sabina Tahirovic, Matthias Brendel, Jochen Herms and Lars Paeger, August 8, 2025, Nature communications.
Two: 10.1038 / S41467-025-62500-8

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