Lost Sense of Smell May Signal Early Alzheimer’s Disease, Mouse Study Suggests

Clumps of the Alzheimer’s-related protein amyloid-beta in nerves around organs related to smell may explain why people in the early stages of the disease lose their ability to detect odors, a study reports.

Researchers at the Daegu Gyeungbuk Institute of Science and Technology in South Korea also discovered that loss of the ability to smell occurs before cognitive loss, at least in an animal model of the disease.

Their discoveries add to efforts to identify factors that doctors could use to determine who is likely to develop Alzheimer’s. They also pave the way for similar studies in humans.

The study appeared in the journal Cell Death & Disease. Its title was “Differential spatial expression of peripheral olfactory neuron-derived BACE1 induces olfactory impairment by region-specific accumulation of β-amyloid oligomer.”

“We have discovered an important clue to predict the onset of Alzheimer’s disease in the early stage by identifying a mechanism of beta-amyloid expression in the initial stage of Alzheimer’s that was unknown until now,” Moon Cheil, a professor in the institute’s Department of Brain and Cognitive Sciences, said in a press release. He was the senior author of the study.

To reach the conclusion that there is a link between beta-amyloid clumping and loss of smell, the researchers studied mice carrying a mutation that makes them prone to developing Alzheimer’s.

The team noted that the animals lost their sense of smell before showing signs of cognitive decline. This was evident when the mice performed poorly in tests where researchers hid pieces of food.

Researchers said the mice also lost neurons that are involved in sending olfactory signals to the brain. Interestingly, they found increased BACE1 enyzme activity in both the main part of the mice’s olfactory system and in nerve endings in their nasal epithelium. BACE1 plays a role in the production of amyloid-beta in the brain.

Until this study, most researchers believed that amyloid-beta formed only in the central nervous system. But the Daegu experiments showed that the protein was also present around olfactory nerves. Tests in lab-grown olfactory nerve cells showed that the amyloid proteins were capable of killing the neurons.

With an increased focus these days on preventing Alzheimer’s, the researchers argued that their findings might be used to identify people who are likely to develop the disease.

The team plans additional studies on how the sense of smell could be used to develop new ways of diagnosing Alzheimer’s early.