Loss of Smell May Be an Early Sign of Alzheimer’s Disease, Study Finds

Discover why a reduced sense of smell could be a crucial early sign of Alzheimer's. Learn how brain immune activity may cause this symptom years before memory loss.

A reduced sense of smell may be one of the first signs of Alzheimer’s disease, showing up years before noticeable memory issues start. Scientists at the German Center for Neurodegenerative Diseases (DZNE) and Ludwig Maximilian University of Munich have discovered that this change in smell might be connected to early immune activity in the brain. Their findings were published in the journal Nature Communications and were based on studies involving mice, human brain tissue, and brain imaging scans.

Brain Immune Role

The brain’s immune cells, known as microglia, may begin to remove important nerve connections related to smell. These connections link the olfactory bulb, which processes smells from the nose, with the locus coeruleus, a part of the brainstem involved in several bodily functions, such as sleep, attention, and sensory processing.

Nerve Disruption

Dr Lars Paeger, a researcher at DZNE and LMU, explained that early changes in Alzheimer’s can affect long nerve fibres connecting these two brain regions.

When these fibres are altered, the immune system might mistakenly identify them as damaged. As a result, microglia begin to break them down, which affects the brain’s ability to process smells.

Cell Changes

The research team found a significant change in the structure of these nerve cells. A fatty molecule called phosphatidylserine, which usually remains inside the cell membrane, was found on the outside instead. This acts as a signal to immune cells, telling them to remove the affected connection.

According to Paeger, this "eat-me" signal is part of a normal process called synaptic pruning, where the brain removes unnecessary connections. However, in this case, the researchers think that abnormal nerve activity linked to Alzheimer’s disease may cause changes in the cell membrane, leading to the over-removal of important connections.

Multiple Evidence

The conclusions are supported by several types of evidence. Scientists studied mice with Alzheimer’s-like symptoms, examined brain tissue from people who had the disease, and analysed PET scans of patients with Alzheimer’s or mild cognitive impairment. Across all these studies, similar patterns of early nerve damage in smell-related pathways were observed.

Early Mechanism

The study also pointed out that while smell loss in Alzheimer’s has been known for some time, the biological reason behind it was not clear. The new research suggests that an immune-related process might be the cause, and that it starts very early in the disease, before major memory problems develop.

The findings could also be important for treatment. New therapies that target amyloid-beta antibodies are designed to slow disease progression and are most effective when used early.

Researchers believe that using smell loss as an early indicator, along with other tests, could help identify individuals at higher risk of developing Alzheimer’s disease. This could lead to earlier diagnosis, better monitoring, and improved chances of successful treatment.