What causes Alzheimer’s? New link with type 2 diabetes

What causes Alzheimer’s disease? We’ve spent decades looking at the link between Alzheimer’s disease and a protein called amyloid beta(Aβ). But the truth of the matter is we don’t know if Aβ causes it or is simply a biomarker.

One heavily explored relationship is the link between type 2 diabetes and Alzheimer’s diseases. It’s clear from the data that insulin resistance impairs the ability to remove Aβ from the brain. In fact, researchers often refer to Alzheimer’s disease as Type 3 diabetes, or insulin resistance of the brain.

A new paper gives us a glimpse into how this may happen. Their research implies that Aβ isn’t just a junk protein clogging up our brain.

In fact, it suggests that the pancreas and insulin-sensitive tissues secrete Aβ. Based on their findings, it plays a role in regulating insulin secretion. This provides new alternative evidence as to what causes Alzheimer’s disease.

How Aβ regulates insulin and blood glucose levels

When we consume food, absorption from the gut increases our blood glucose. As our blood glucose level rises, this stimulates islet cells in the pancreas to secrete insulin. Insulin circulates and binds to insulin sensitive tissues, causing them to take in glucose, decreasing blood glucose.

But, it appears that more is going on than what this simplistic model shows. Instead, when stimulated with glucose, the islet cells in the pancreas also secrete Aβ. They called this primary secretion.

Then, as insulin circulates and binds to peripheral tissues such as muscle, they secrete Aβ with their tissue-specific signaling molecules as well. They called this secondary secretion.

The researchers believe that, while glucose is the primary driver of insulin secretion, Aβ helps fine tune it. The secretion of Aβ by the pancreas AND insulin-sensitive tissues recirculates back to the pancreas and inhibits insulin secretion.

This helps prevent the secretion of too much insulin and fine tunes blood glucose.

What causes Alzheimer's disease and insulin resistance

How this plays a role in what causes Alzheimer’s disease

As mentioned, there is clearly a link between type 2 diabetes and Alzheimer’s disease. But we don’t know how or why this relationship works, and this provides some direction.

The authors posit a couple of ways that this may work. First, Aβ levels in the brain and circulation are separate. Consequently, Aβ in the brain must be transported out of the brain and in to the circulation.

However, chronically high levels of Aβ in the circulation may impair the transport of Aβ out of the brain. Furthermore, excessive insulin in the circulation may cross the blood brain barrier and prevent the breakdown of Aβ.

The second theory is that Aβ in the circulation may damage blood vessels in the blood brain barrier. In this model, the housekeeping system in the brain known as the glymphatic system becomes impaired.

This glymphatic system follows a circadian rhythm, becoming more active at night while we sleep. During this time, it effectively removes toxins from the brain, which may include Aβ. We covered this in a blog you can check out here.

This impairment of the glymphatic system would allow Aβ to accumulate in the brain. There is evidence that this system is impaired in people with diabetes, leading to dementia.


This research provides compelling evidence of the link between type 2 diabetes and Alzheimer’s disease. It’s important to point out that this doesn’t mean that Aβ is what causes Alzheimer’s disease.

As has been previously mentioned, accumulation of Aβ may simply be a marker of impaired housekeeping in the brain, so-to-speak. If this is the case, Aβ is simply the canary in the coal mine telling us something is wrong.

With this new role of Aβ in regulating insulin and blood glucose, the importance of maintaining healthy insulin sensitivity through life to reduce the risk of Alzheimer’s disease cannot be overstated.

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