The Grapevine

Having Type 2 Diabetes May Increase Risk Of Alzheimer's Due To Amyloid Formation In Pancreas

Alzheimer's and Diabetes
The formation of amyloid deposits in the pancreas could lead to their development in the brain, causing Alzheimer's disease. Photo courtesy of Shutterstock

While it may not always seem like it, many, if not all, of the chronic diseases we know of today are interrelated. The onset of one disease, such as obesity, can most certainly lead to the development of another one like heart disease or cancer. This can apply to more improbable diseases too, as a new study from Uppsala University in Sweden shows; the amyloid deposits that characterize Alzheimer’s disease may begin forming in the pancreas of type 2 diabetics.

The research sought to uncover how the two diseases are connected by a process called amyloidosis, which occurs in both Alzheimer’s and diabetes patients. Amyloidosis is the process by which misfolded proteins accumulate into fibrous deposits that are resistant to degradation. In the pancreases of type 2 diabetics, amyloid is produced from its precursor, islet amyloid polypeptide (IAPP, or amylin), which is a secretory product of insulin-producing beta cells. This process causes a cascade of body reactions; as IAPP builds in the pancreas, it kills beta cells, worsening diabetes, and pushing along the development of the beta-amyloid deposits.

Dr. Gunilla Westermark and her team were interested in seeing whether these accumulations of IAPP could travel to the brain, and from the brain to the pancreas. IAPP has binding sites in the brain that are suspected to play a role in satiety and emptying of the stomach. If this is the case, then it might explain where these amyloid deposits come from as well as why type 2 diabetics are more than twice as likely to develop Alzheimer’s.

For the study, the team injected mice expressing human IAPP with preformed fibrils of synthetic IAPP, proIAPP (a precursor to IAPP), or beta-amyloid. After the mice spent 10 months eating a fatty diet, the researchers found that amyloid concentrations had increased among all three fibrils in the pancreases’ hormone-producing cell clusters, called islets. Because the deposits weren’t found elsewhere in the body, such as in the liver or kidneys, the researchers concluded that beta-amyloid from the brain could seed the production of amyloid in the pancreas — the brain-to-pancreas connection.

Then, in order to see if IAPP and beta-amyloid could both appear in the brain, the researchers looked at tissue samples of the temporal cortex, which plays a role in storing memories, in Alzheimer’s patients as well as patients with frontotemporal dementia, progressive supranuclear palsy, or no brain disease at all. Although they found IAPP in all samples, those with Alzheimer’s had concentrations 1.4 times higher than those with healthy brains.

“It’s not clear if IAPP found in [the] brain is locally produced or derived from pancreatic beta-cells,” Westermark said in a press release. “Cross-seeding by other amyloid aggregates or perhaps by other types of aggregates offers one possible mechanism for initiation of amyloid formation.” In other words, IAPP may have the ability to travel between the pancreas and the brain, building plaques in both.

Source: Oskarsson M, Paulsson J, Schultz S, Ingelsson M, Westermark P, Westermark G. In vivo Seeding and Cross-seeding of Localized Amyloidosis: A Molecular Link between Type 2 Diabetes and Alzheimer Disease. The American Journal of Pathology. 2015. 

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