9/10 Alzheimer’s Patients Lose Sense of Smell—Is Beta-Amyloid the Culprit?

In a new mice study, researchers showed that beta-amyloid — the toxic protein linked to Alzheimer’s — can gum up the olfactory system and could be a reason for the partial loss of smell that people with Alzheimer’s tend to experience. 

The deterioration of one’s senses – the ability to taste, smell and hear — can show up as early symptoms of the Alzheimer’s disease, even before the hallmark symptom of memory loss. Among these sensory changes, a partial loss of one’s sense of smell is considered a strong indicator of the onset of the disease, affecting some nine out of 10 people living with Alzheimer’s. Hyposmia (decreased sense of smell) and agnosia (loss of smell) may appear with mild cognitive impairment and can worsen as the condition progresses.  

But there is much about this telltale sign that scientists have yet to understand. Now, in a recent study published in the Alzheimer’s Research and Therapy, scientists from the Daegu Gyeungbuk Institute of Science and Technology in South Korea tried to probe deeper into why this change happens, seeking to understand the mechanisms of olfactory dysfunction in Alzheimer’s.

The researchers looked at how olfactory sensory neurons that detect odor are affected by beta-amyloid, a toxic protein that aggregates in the brains of people with Alzheimer’s. They examined the region-specific degeneration of sensory neurons for clues as to why people living with Alzheimer’s could smell partially, responding to some odors and not others. 

In 2017, the same researchers studied why the loss of smell occurred in Alzheimer’s. This was in the backdrop of a large aging population in South Korea that has made dementia a social problem. Led by Professor Cheil Moon, they didn’t limit their study of loss of smell to the brain and the central nervous system. Instead they also examined the olfactory system which hadn’t been focused on before in other studies. They then found the accumulation of beta-amyloid —  a known biomarker  for Alzheimer’s previously found only in the brain — in the olfactory system. This showed a link between the presence of beta-amyloid in the olfactory system and the loss of smell that people living with Alzheimer’s experience. 

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In their recent study, the team used a mouse model and tested if mice could sniff out hidden foods based on their scents, and whether they could differentiate between the scents. They found that the mice responded to some scents and didn’t respond to others. They also discovered anatomical defects in some olfactory regions. This could be due to neuronal deficits in specific areas of their olfactory system, the researchers noted.

They also discovered that the difference in accumulation of beta-amyloid protein determined the sense of smell. The beta-amyloid protein they found was uneven across different anatomical regions of the olfactory system. Those regions that showed higher levels of beta-amyloid also indicated lower activation of olfactory sensory neurons and thus, a lower sense of smell. This could explain why there was a partial loss of smell in Alzheimer’s. 

Their findings fit into a bigger picture of existing research on this symptom: One well-known past study, while it was hard to replicate, was the peanut butter Alzheimer’s test at the University of Florida, in which older adults were asked to smell a dollop of peanut butter to help detect early-stage Alzheimer’s. Researchers have also found that older people who can smell scents such as roses, turpentine, paint thinner and lemons are less likely to develop dementia. 

According to the researchers, learning more about what causes the loss of smell in Alzheimer’s and how it occurs could be used to detect Alzheimer’s early. “Partial loss of smell can be a potential diagnostic strategy for the early screening of persons at risk of developing Alzheimer’s,” Moon said in a news release.“The findings of our study enhance the understanding of the association between Alzheimer’s progression and beta-amyloid accumulation in the olfactory system that can further reveal interesting therapeutic targets.”