Amyloid Formation – The missing link between Diabetes and Alzheimer’s ?

 

 

amyloid formation

Amyloid-beta in red surrounded by astrocytes in green

Researchers find a link between amyloid formation in type II diabetes and Alzheimer’s disease which might help explain the increased risk of dementia in diabetes patients.

In Alzheimer’s disease there’s a build up of misfolded proteins forming plaques in the brain, eventually killing brain cells causing dementia symptoms. These misfolded proteins, amyloids, are also found in other diseases, one being type II diabetes where amyloid proteins are found in the insulin producing islets of Langerhans. Build up of the misfolded protein kills insulin producing beta cells worsening diabetes symptoms. Now new research find how amyloid plaques in diabetes and Alzheimer’s are linked.

Amyloid Formation – The missing link between Diabetes and Alzheimer’s ?

The findings were published in The American Journal of Pathology.

Earlier studies have found that people suffering from type II diabetes also have twice the risk of developing Alzheimer’s disease. Until now researchers have been unsure how these diseases are linked. This study suggests that the increased risk is caused by pancreas amyloid seeding amyloid plaque formation in the brain.

Though misfolded proteins are found in both diabetes and Alzheimer’s diseases they are not the same protein. Brain plaques in Alzheimer’s are made up of amyloid-beta proteins while the accumulation seen in type II diabetes consist of IAPP (islet amyloid polypeptide) formed from a precursor called pro-IAPP.

Could one type of amyloid stimulate formation of plaques made up of different amyloid proteins?

To find out, researchers used mice expressing the human form of amyloid protein found in type II diabetes, IAPP. The mice were injected with three different forms of amyloid proteins, synthetic IAPP, pro-IAPP and amyloid-beta, to find if any of these could seed formation of amyloid plaques .

After mice were fed a high fat diet for 10 months researchers used an amyloid specific dye to see where amyloid plaques had formed. They found that the number of pancreas islets with amyloid deposits had significantly increased in mice injected with any of the three types of amyloids. The accumulated amyloid deposits all consisted of IAPP amyloids.

The study found that injecting different amyloid proteins can seed amyloid formation in the pancreas. The amyloid causing dementia, amyloid-beta, can cross-seed IAPP amyloid plaques in the pancreas.

Analyzing tissue samples from human pancreases researchers found that patients with diabetes tested positive for IAPP amyloids but not amyloid beta. In the Brain tissue samples the story was reversed. Brain tissue from controls, dementia patients and Alzheimer’s patients all had IAPP proteins in brain plaques. The difference was that Alzheimer’s patients had greater concentrations of IAPP, 1.4 times higher than non-AD patients.

Though it remains unclear if the IAPP is made in the brain or comes from the pancreas this find provide a reasonable mechanism why type II diabetes patients are more likely to develop Alzheimer’s.

Image Credit: Zerd Noneofyourbusiness via flickr.com, CC BY-NC-SA 2.0