The new study published in the American Journal of Pathology highlights how characteristics of one disease may contribute to the formation of another. Amyloid deposits can occur in many diseases including Alzheimer disease and type 2 diabetes. They are caused by protein deposits that accumulate to form plaques. Very little was known as to how these proteins were formed, how they interact and if there was a cross reference to different diseases. Islet amyloid can be found in pancreatic cells called islets of Langerhans in almost all patients with type 2 diabetes. Islet amyloid is made up of islet amyloid polypeptide (IAPP), which is derived from its precursor proIAPP. Accumulation of IAPP can lead to beta-cell death. In the brain, deposits of beta-amyloid in the cortex and blood vessels are characteristic findings in AD.
Previous studies have revealed that patients with type 2 diabetes have a 2 fold greater risk of developing Alzheimer’s disease. The research study, from Sweden’s Uppsala University, connected the dots between the two condition and determined that amyloid deposits can spread from one organ to another.
“Several soluble proteins are amyloid forming in humans. Independent of protein origin, the fibrils produced are morphologically similar,” said Gunilla T. Westermark, PhD, Department of Medical Cell Biology at Uppsala University (Sweden). “There is a potential for structures with amyloid-seeding ability to induce both homologous and heterologous fibril growth. Heterologous seeding between IAPP and beta-amyloid may represent a molecular link between AD and T2D.”
The researchers used mice models and human tissue to test their hypothesis. The results demonstrate for the first time that fibril injections could seed amyloid formation in the pancreas and also that brain amyloid could cross-seed fibril formation in the pancreas.
In human tissue experiments the investigators analyzed human tissues from the pancreas and brain. They found that pancreas sections with islet amyloid from patients diagnosed with type 2 diabetes showed no beta-amyloid immunoreactivity, whereas all samples were immunoreactive for islet amyloid polypeptide found in the pancreas. The researchers further analyzed samples from the temporal cortex from Alzheimer patients and age-matched non-Alzheimer patients with frontotemporal dementia, progressive supranuclear palsy (PSP), or no neurological diagnosis. It was determined that there was islet amyloid polypeptide reactivity in all the samples with Alzheimer Disease samples contained 1.4-times higher islet amyloid polypeptiide concentrations.
“It is not clear if IAPP found in brain is locally produced or derived from pancreatic beta-cells,” commented Dr. Westermark. “Cross-seeding by other amyloid aggregates or perhaps by other types of aggregates offers one possible mechanism for initiation of amyloid formation. Interactions between amyloid and other aggregation-prone proteins may be of great importance in the development of protein-misfolding diseases.”
“In vivo Seeding and Cross-seeding of Localized Amyloidosis: A Molecular Link between Type 2 Diabetes and Alzheimer Disease,” by Marie E. Oskarsson, Johan F. Paulsson, Sebastian W. Schultz, Martin Ingelsson, Per Westermark, and Gunilla T. Westermark DOI: 10.1016/j.ajpath.2014.11.016. This article appears online ahead of The American Journal of Pathology, Volume 185, Issue 3 (March 2015) published by Elsevier.