News

Exploring the Diabetes and Alzheimer’s Link

Posted: Oct. 14, 2010

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.

 

 

 

 

 

 

 

 

Poll Shows Americans favor increase in federal funding for Alzheimer’s research

Posted: Oct. 8, 2010

A new poll shows 88 percent of registered voters believe it is important for Congress to make Alzheimer's a priority despite a growing budget deficit. The poll was conducted by USAgainst Alzheimer's, a Washington, DC group formed specifically to “mobilize America to stop Alzheimer’s by 2020” through aggressive lobbying and support of legislators who support increased funding for Alzheimer’s care and research. Cure Alzheimer’s Fund applauds their efforts and certainly agrees with the need for more resources and a focused strategy at the National level.

Alzheimer’s and Diabetes Link

Posted: Oct. 6, 2010

Alz Forum, the dynamic online scientific knowledge base that reports on the latest Alzheimer's scientific research, has a good article on the recent discovery by Cure Alzheimer’s Fund Researcher Sam Gandy on a link between Alzheimer’s and diabetes, arising from the Alzheimer’s Genome Project which identified new Alzheimer’s gene candidates.

Madolyn Bowman Rogers writes:

Two pernicious disorders of late life, Alzheimer disease and diabetes, may be tied together by a common connection with a pathway that sorts and trafficks proteins such as APP within cells, new research suggests. In the September 29 issue of the Journal of Neuroscience, researchers led by Sam Gandy at Mount Sinai School of Medicine in New York City report that the sorting protein SorCS1 reduces Aβ generation when overexpressed, and conversely is associated with higher levels of Aβ in female mice when underexpressed. SorCS1 has been genetically linked to both diabetes and AD. The convergence of these two diseases on SorCS1 may help explain why having diabetes is a risk factor for contracting Alzheimer’s. The results also suggest a potential new pathway for therapeutic intervention into both disorders.

This paper is important, said Thomas Willnow of the Max-Delbrueck-Center for Molecular Medicine in Berlin, Germany, as it adds pieces to help solve the puzzle of the intracellular trafficking of APP. The data also fit well with previous reports finding that trafficking pathways may be altered in AD, Willnow said. “I think it all adds up and points to a very important aspect of [AD] pathology.”

Read the full article “APP Sorting Protein May Link Alzheimer’s and Diabetes” >

We congratulate Dr. Gandy on this important work and are proud to have helped support it!

 

 

New Research Reveals Common Genetic Risk Factor Linking Alzheimer’s Disease and Type 2 Diabetes

Posted: Sep. 30, 2010

Potential for New Therapies to Treat both Diseases

The discovery of a molecular mechanism linking Alzheimer’s disease and Type 2 Diabetes could lead to exciting new drugs to treat both devastating diseases, according to new research published this week in The Journal of Neuroscience.  Researchers found that the gene for a protein called SorCS1, which is linked with Type 2 Diabetes, participates directly in the pathogenesis of Alzheimer’s.

Supported by Cure Alzheimer’s Fund (CAF), the research was led by Dr. Sam Gandy, professor in Alzheimer’s disease research at the Mount Sinai School of Medicine and Dr. Rudy Tanzi, PhD, Harvard University’s Joseph P. and Rose F. Kennedy Professor of Neurology and Director of Genetics and Aging Research Unit. Both are members of the CAF research consortium.  Also part of the team were University of Wisconsin geneticist Alan Attie, PhD, who discovered the linkage of SorCS1 to diabetes in 2007, and Columbia University Alzheimer’s researcher Scott Small, MD.  Rachel Lane, Ph.D., a postdoctoral fellow at Mount Sinai, and Summer Raines, Ph.D., a graduate student at the University of Wisconsin performed the research and shared first authorship.

“Alzheimer’s and Type 2 Diabetes are complex diseases and the risks of both include high cholesterol, obesity and vasculopathy, but these factors are highly interrelated and the challenge has been finding a clear starting point to understand the relationship between the two diseases,” said Gandy. “Our research has revealed a molecular mechanism in the gene SorCS1 that is shared by Alzheimer’s and type 2 diabetes. These findings could open up new doors for more effective treatments for both diseases.”

The research found that the brains of mice genetically deficient in SorCS1, created by Raines and Attie, showed increased levels of amyloid-beta (Abeta), known to play a key role in the onset of Alzheimer’s disease. Meanwhile cells engineered to express high levels of SorCS1 generated low levels of Abeta.

The SorCS1-deficient mice also were found to have abnormally low levels of another protein called Vps35, a profile that Dr. Small linked to Alzheimer’s disease in a 2005 study.  Thus the low SorCS1 might cause levels of Vps35 to go down and lead to the increased formation of Abeta in the mice, and, presumably, Alzheimer’s, in humans.  For the moment, this work provides potential insights and new targets but therapeutic outcomes will require more research.

“Alzheimer’s and Type 2 Diabetes are major causes of illness and death in the elderly and these findings could lead to new drug targets to treat both diseases by increasing levels of SorCS1 or Vps35,” Dr. Tanzi said.  “While further research is needed to find the link between SorCS1 and Vps35, these data will open many new doors.”

“Dr. Gandy and Dr. Tanzi are on the cutting edge of Alzheimer’s research and always take an innovative approach to any challenge they face,” said Tim Armour, president and CEO of Cure Alzheimer’s Fund. “We, at Cure Alzheimer’s Fund, are proud of their work and the hope it offers to the millions of Americans and their families affected by both of these devastating diseases.”

CAF Supported Research by Sam Gandy Reveals Diabetes and Alzheimer’s Link

Posted: Sep. 30, 2010

Cure Alzheimer’s Fund Research Consortium member, Sam Gandy, published research this week in The Journal of Neuroscience linking genes from Alzheimer’s and Type 2 Diabetes. Gandy and other researchers found that the gene for a protein called SorCS1, which is associated with Type 2 Diabetes, participates directly in the pathogenesis of Alzheimer’s.

This work is critically important because it gives new targets for therapy and provides new ways of looking at and understanding both diseases. Watch coverage of this important work on MSN and NBC Nightly News.

Link to video>

Read more about this and how it comes directly from the work of Cure Alzheimer’s Fund’s AGP project conducted by Rudy Tanzi at Mass General Hospital>

Read about this research in Medical News Today>

White House Briefing on Challenge of Alzheimer's

Posted: Sep. 29, 2010

Cure Alzheimer's Fund President, Tim Armour, and Research Consortium Chairman, Rudy Tanzi, were featured in a video from the White House on World Alzheimer's Day. Armour and Tanzi were invited to serve on a special panel to discuss the serious challenge Alzheimer's poses to our nation. Panelists concluded that Alzheimer's is going to have an increasingly devestating effect and all agreed we cannot wait; more must be done to fund research to put an end to this disease as soon as possible.

Read our previous blog on this event>

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Univ. of Pittsburgh and MGH Alzheimer's Project Receives $400,000 Grant

Posted: Sep. 22, 2010

Cure Alzheimer's Fund announced it's latest grant at an event this morning in Pittsburgh. The announcement was covered yesterday in the Pittsburgh Post-Gazette. The article highlighted Cure Alzheimer's Fund's strategic approach, the organization's history and profiled Chairman Jeff Morby.

Read the article in the Pittsburgh Post-Gazette>

Read the Press Release>

 

Univ. of Pittsburgh, Mass General Hospital awarded Alzheimer’s Research Grant for Innovative Collaboration on Derivatives to Treat Disease

Posted: Sep. 22, 2010

Univ. of Pittsburgh’s Dr. William Klunk & MGH’s Dr. Rudolph Tanzi to Discuss Joint Effort At World Alzheimer’s Day University of Pittsburgh Forum

Pittsburgh  – Bringing together two esteemed institutions known for groundbreaking Alzheimer’s research, Cure Alzheimer’s Fund has awarded the University of Pittsburgh a $300,000 grant and Massachusetts General Hospital/Harvard (MGH) a $100,000 grant to fund an innovative joint research project on Alzheimer’s disease, which currently affects 5.3 million Americans and their families.

Jeffrey Morby, Cure Alzheimer’s Fund (CAF) Chairman and co-founder and Pittsburgh resident, praised the project and its novel approach to treatment and prevention of Alzheimer’s disease. “As Chairman and co-founder with my wife Jacqui of the Cure Alzheimer’s Fund, we have looked forward to the opportunity to help bring these two prestigious institutions together for this great cause,” said Morby, who will announce the grant at a University of Pittsburgh World Alzheimer’s Day Forum. “This pioneering collaborative research on Alzheimer’s disease will help to better understand this devastating disease and could lead to better treatment, ways to reverse its effects and even find a cure.”

This project blends the unparalleled expertise in Alzheimer’s research of these two premier institutions. MGH has identified the largest number of candidate Alzheimer’s genes in the world while University of Pittsburgh has developed a unique and powerful method to analyze the brain for signs of Alzheimer’s pathology.

Funded exclusively by Cure Alzheimer’s Fund, the project will focus on advanced work identifying key components of Alzheimer’s pathology in living Alzheimer’s patients, which will enable more rapid development of effective therapies against the disease. The team is headed by University of Pittsburgh’s William Klunk, MD, PhD, Professor of Psychiatry and Neurology and Co-Director of the Alzheimer’s Disease Research Center, and MGH’s Rudy Tanzi, PhD, Harvard University’s Joseph P. and Rose F. Kennedy Professor of Neurology and Director of Genetics and Aging Research Unit, and Chairman of the Cure Alzheimer’s Fund Research Consortium.

University of Pittsburgh and MGH researchers will identify and characterize novel curcumin-like (CLDs) derivatives for the treatment and early prevention of Alzheimer’s disease. Several recent studies have suggested promise for treatment of Alzheimer’s with the major component of curry spice or turmeric called curcumin. However, the major drawback in this treatment is the rapid breakdown of the curcumin by the stomach and liver leads to poor bioavailability or absorption by the brain. The purpose of the research study is to develop means of overcoming obstacles to rapid breakdown and creating  methodologies for precisely delivering curcumin derivatives to appropriate locations within the brain.

Dr. Tanzi’s team will further study the properties of these CLDs in variety of assays and animal models for effects on the amyloid beta protein precursor (APP) and the generation of Abeta, a protein that is widely believed to drive Alzheimer’s disease pathology.

University of Pittsburgh will synthesize the CLDs and test their Abeta-binding affinities as well as their bioavailabilities, brain entry and toxicity characteristics. Combining their results with the work of Dr. Tanzi’s lab, researchers will design and synthesize additional novel CLDs and test these compounds.

G. Nicolas Beckwith III, Chairperson of the University of Pittsburgh Board of Directors applauded the unique partnership and the work of the Cure Alzheimer’s Fund, “Like University of Pittsburgh, Cure Alzheimer’s Fund understands that research is where we must start to find more effective treatments and a possible cure for this devastating disease.”

 

Tanzi and Armour participants in White House Sponsored Meeting of the Status of Alzheimer’s Research

Posted: Sep. 22, 2010

The status of research in the United States to find a cure for Alzheimer’s disease was the focus of discussion at a White House sponsored event on World Alzheimer’s Day, Tuesday, September 21, 2010.

Cure Alzheimer’s Fund Research Consortium Chair Dr. Rudolph Tanzi and Tim Armour, President of the Cure Alzheimer’s Fund, participated on a scientific panel at the White House event before a select audience of White House senior staff policymakers, leading scientists, advocates and others including Jeff Morby, Chairman and co-founder of Cure Alzheimer’s Fund, and Melody Barnes, Director, White House Domestic Policy Council. The topics covered included the current status of biomarker identification for the disease, current thinking about prevention, the strength of the drug pipeline for Alzheimer’s and possible policy initiatives to accelerate progress toward a cure.

Panelists agreed that more funding from both the public and private sectors needs to be invested in finding a cure and better treatments; and more aggressive efforts at creating public-private partnerships to provide focus for research efforts is crucial.

The clear message to come from the meeting is that Alzheimer’s is having a devastating impact not only on the growing number of patients and their families but on the national budget as well. With the Federal government spending $172 Billion on care for Alzheimer’s patients through Medicare and Medicaid in 2010, and the National Institutes of Health able to invest only $470 million in basic research, the “cure” will be a long time in coming if there is not a rapid change in national priorities.

All agreed that we cannot afford to wait, and the development of effective therapies to prevent or stop Alzheimer’s has to be a national priority, backed by a clear strategy and resources to implement it.

 

Hobbling Science and Scientists

Posted: Sep. 20, 2010

William Sahlman, the senior associate dean for external relations at Harvard Business School, wrote an excellent op-ed in the Boston Globe yesterday. We couldn’t agree more with his assessment of the dreadful funding environment for scientific research.  His piece helps us understand the difficulties of making productive progress in disease research by taking a look at how research labs work. While this piece was inspired by the recent stem-cell research issue, it is applicable to most research including Alzheimer's.

Read the op-ed in the Boston Globe>