The sense of smell is surprisingly connected to the risk of developing Alzheimer’s disease, and this link is becoming clearer through recent scientific discoveries. It turns out that changes in the brain’s smell-processing system may be one of the earliest signs of Alzheimer’s, even before memory problems or other cognitive symptoms appear.
At the heart of this connection is a small but crucial brain region called the **locus coeruleus**. This area is responsible for producing a chemical called **noradrenaline** (also known as norepinephrine), which helps regulate many important functions such as blood flow in the brain, sleep-wake cycles, attention, and sensory processing—including how we perceive smells. The locus coeruleus sends out long nerve fibers to various parts of the brain, including the **olfactory bulb**, which is the first brain region that processes smells coming from the nose.
In early Alzheimer’s disease, these noradrenaline-producing nerve fibers connecting the locus coeruleus to the olfactory bulb begin to deteriorate. This loss is not due to damage in the nose or the olfactory bulb itself but rather because the brain’s immune cells, called **microglia**, mistakenly attack and remove these fibers. Microglia normally help keep the brain healthy by pruning away damaged or unnecessary connections, but in Alzheimer’s, they seem to target these noradrenaline fibers too aggressively.
What triggers microglia to attack these fibers is a change in the nerve cell membranes. Normally, a fatty molecule called **phosphatidylserine** is located on the inside of the nerve cell membrane. However, in early Alzheimer’s, this molecule flips to the outside, acting like a distress signal that tells microglia, “Eat me.” This causes microglia to break down the noradrenaline fibers connecting the locus coeruleus and the olfactory bulb.
The loss of these fibers disrupts the brain’s ability to process smells properly, leading to a decline in the sense of smell. This decline can be detected through simple smell identification tests, which have shown that people with mild cognitive impairment or early Alzheimer’s perform worse than healthy individuals. Interestingly, this smell loss is specific to Alzheimer’s and differs from smell problems in other diseases like Parkinson’s, where the sensory neurons in the nose are directly affected.
Because these changes occur very early—before widespread brain damage or memory loss—testing for smell loss could become a valuable tool for early detection of Alzheimer’s risk. Brain imaging studies have also found increased microglial activity in the olfactory bulb of people with mild cognitive impairment, supporting the idea that immune system changes in this region are an early event in the disease process.
This discovery opens up exciting possibilities for intervention. If treatments can be developed to protect or restore the noradrenaline fibers or to regulate microglial activity, it might be possible to slow down or prevent the progression of Alzheimer’s at a stage when the brain is still relatively intact.
In summary, the surprising connection between the sense of smell and Alzheimer’s risk lies in the early immune-driven damage to noradrenaline-producing nerve fibers linking the locus coeruleus and the olfactory bulb. This damage leads to smell loss, which can serve as an early warning sign of the disease, potentially years before cognitive symptoms emerge. Understanding this connection better could revolutionize how Alzheimer’s is detected and treated in the future.
