Researchers hypothesize part of the body’s natural defense against infection may underlie both diabetes and AD.
Cure Alzheimer’s researchers Dr. Rudy Tanzi, chairman of CAF’s Research Consortium and director of the Massachusetts General Genetics and Aging Research Unit, and Dr. Robert Moir from Massachusetts General Hospital were awarded funding from the Helmsley Trust through Cure Alzheimer’s Fund to explore the similarities between the protein amylin in diabetes and its analog in Alzheimer’s, both hallmarks of each disease’s pathology.
“We are deeply grateful for this generous gift from the Leona M. and Harry B. Helmsley Charitable Trust for a $600,000 grant to Cure Alzheimer’s Fund to be paid over two years,” said Tim Armour, president of Cure Alzheimer’s Fund. “This is an exceptional opportunity that is going to allow significant progress into better understanding the twin rising epidemics of diabetes and Alzheimer’s.”
Diabetes mellitus is estimated to affect some 23.6 million Americans today with incidence rates increasing every decade. People most at risk from type II (commonly called mature or late-onset) diabetes are in the same elderly population at risk of Alzheimer’s disease.
A pathological hallmark of both diabetes and Alzheimer’s is the deposition of insoluble proteinaceous deposits called amyloid. Diabetes and Alzheimer’s long have been known to share a broad array of clinical features and a large body of evidence suggests the pathologies of these two disorders are strongly linked. However, as yet no common molecular mechanism has been identified that can explain the long list of epidemiological commonalities between diabetes and Alzheimer’s.
The research, supported by the Helmsley Trust and Cure Alzheimer’s Fund, will focus on the toxic amyloid deposits thought to mediate cellular and tissue degeneration in patients with diabetes and patients with AD and, more specifically, will investigate the activities of the proteins that form diabetic and AD amyloids (for Alzheimer’s this is the Abeta peptide, and for diabetes it is a peptide called amylin).
Drs. Moir and Tanzi recently discovered that the Amyloid-beta protein, a key contributor and acknowledged by most researchers as the “key bad guy” in Alzheimer’s pathology, may have an unsuspected side. The prevailing theory was that Abeta has no function other than as a waste product created by the brain. But research published in the March issue of the journal PLoS One, by Drs. Moir and Tanzi show the protein may be part of the body’s natural defense against infection. This research suggests that Abeta has a very positive function—the peptide may be a natural antibiotic protecting the brain from invading microbes and defending against parasites.
“These data change the way we look at Abeta,” says Dr. Tanzi. “For years, we thought that Abeta was just metabolic garbage produced as a byproduct of other processes within the brain, but new data suggest it is a normal component of the brain’s innate immune system.” Rob Moir adds “Our laboratory has recently shown that Abeta is, in fact, a potent naturally occurring antibiotic. In preliminary experiments we have shown that amylin also appears to be a potent natural antibiotic.”
It appears both proteins may be members of an ancient family of biomolecules called antimicrobial peptides (AMPs) that are the first line of defense against invading organisms. AMPs are the foot soldiers of our innate immune system- an older defense system separate from the antibodies and cells of adaptive immunity.
Notably, while AMPs are critically important for killing invading pathogens, many can also cause collateral damage to host tissue. Aggregation is a key mechanism for the function of AMPs and at least five cause amyloid pathologies. Moir and Tanzi’s findings link, for the first time, the pathologies of diabetes and AD at the molecular level by identifying a common and totally unanticipated antimicrobial function for amylin and Abeta.
These findings suggest that the same or similar site-specific overactive innate immune response to a perceived infection (real or incorrectly identified) may underlie both diabetes and AD. In the brain this response causes Alzheimer’s, when it occurs in the pancreas the result is diabetes.
Confirmation of this hypothesis would prompt a major re-think of the origins of these diseases. In addition, it would identify the pathways of innate immunity as new drug targets for treating, and possibly even preventing diabetes and AD.