News

Find updates on the work of our researchers here, as well as news about recent advances in Alzheimer's science, funding and awareness.

A Flash of Genius Courtesy of the Alzheimer’s Reading Room

Bob DeMarco, the editor of the Alzheimer’s Reading Room, has written a great article on Dr. Rudy Tanzi. The article introduces Dr. Tanzi’s theory on abeta’s role in the human brain, which he describes as “a sudden flash of genius.”  He also writes about his frustration with underfunded research projects and failed drug trials. We cannot agree more!

Dr. Tanzi's new hypothesis "says what we need is the equivalent of a statin for the brain so you can dial it down but not turn it off.” The it being beta amyloid, A-beta.

“It means you don’t want to hit A-beta with a sledgehammer,” Dr. Tanzi said. “It says what we need is the equivalent of a statin for the brain so you can dial it down but not turn it off.”

A sudden flash of genius? Or another bridge to no where?

It is too early to tell. I like this way of thinking outside the box. It seems to me the answer will come from outside the box.

Read more the rest of the article here.

Make sure to check the Alzheimer’s Reading Room regularly. The website is an amazing resource for news on Alzheimer’s.

Bob DeMarco is the founder and editor of the Alzheimer’s Reading Room and the caregiver for his 91-year-old mother.

Q&A from July 22, 2010 Webinar

Thank you again to the attendees of our webinar. Below are the questions we received from participants with answers from Dr. Rudy Tanzi, as well as links to additional information. We have also posted the slides of the presentation here. If you would like to download the PowerPoint file, e-mail Katie Cutler at kcutler@curealz.org.

1.We know the disease process of Alzheimer’s starts long before the actual pathology and symptoms develop. With the growing knowledge of genes involved, wouldn't it be better to try the novel approaches in select individuals long before (say in their 50's) instead of those that have established Alzheimer's? It is disappointing (both to the researchers and the wider Alz community) to hear every time a study results are published, they come up with unsatisfactory results- Dimebon, Rember, Immunisation trials to name a few.

Yes, our goal is to use the genes to predict AD before it strikes and prevent the disease presymptomatically. I agree that it is not constructive to only focus on failed clinical trials of drugs that were not very good to begin with. Let’s focus on the next wave of therapies that have learned from these failures!

Note from Cure Alzheimer’s Fund: Check out more info on this in “Why the Drugs Don’t Work” and in “Sharing Data is Good But We Need to Better Understand Causes of the Disease”

I also wonder if other dementias - vascular/multi-infarct, mixed and frontotemporal dementias will respond to the treatments being developed for Alzheimer’s as the general consensus now appears to be mitochondrial dysfunction and neurotoxicity!

The frontal lobe dementias are based on tangle formation and tau protein abnormalities. So, drugs targeting abeta will most likely not be very helpful. This is why we also need anti-tangle drug programs.

2.What is the difference between genetic predisposition to Alzheimer's disease and familial predisposition to Alzheimer's?

The bottom line is that in familial early onset cases involving mutations in APP, presenilin 1 or presenilin 2, it is not so much predisposition as it is "causation". Any one of the ~200 mutations in these three genes guarantee Alzheimer's when inherited, usually before the patient turns 60 years old. In contrast, in late-onset AD (>60), the APOE4 gene variant increases susceptibility for AD usually between 60 and 80 (~3-fold if one parent transmits it, ~10-fold if both parents transmit it). So, this would be considered a gene variant that predisposes to AD but does not cause the disease with certainty the way the early-onset familial AD gene mutations do. Of course, you can also have familial late-onset AD and here we have found rare mutations in the ADAM10 gene that have strong effects on risk for getting the disease at about 72 years-old. In our Alzheimer's Genome Project, we have found 200 new AD gene candidates. We are currently scouring these genes to find the defects and determine whether they are causative like the early-onset familial AD gene mutations, or predisposing like the APOE 4 variant.

3.Given (as you have found) that beta amyloid has an antibiotic role in the brain, the "Alzheimer's vaccine" seemed to be the perfect Trojan Horse--wiping out beta amyloid and leaving the brain vulnerable to the agents that b-a were fighting off in the first place. You claim PBT2 takes this role of beta amyloid into account, leaving the fighting capacity of beta amyloid while removing the toxic "leftovers" of the fight. Is research also concerned about reducing the foreign cause of aggression in the brain--the agents that beta amyloid is designed to fight off? Is there perhaps an overabundance of these damaging bodies in Alzheimer's cases?

Yes, we are looking into what types of brain insults trigger the innate immune system to produce excess abeta. These insults could range from neurovascular insults, e.g. strokes or traumatic brain injury, to infections.  With regard to the latter, we are focusing on Chlamydia pneumoniae and candida albicans, given our and other’s findings.

Note from Cure Alzheimer’s Fund: For more info check out “Abeta May Have Beneficial Function as Part of the Innate Immune System

4.You said Dimebon was a failure without giving specifics of why it was a failure. From web articles, it's clear it was a failure because it did not improve memory. You also mentioned that another drug showed success (I think it was Bapi) in that it improved higher reasoning. There are plenty anecdotal accounts that Dimebon improved attention, social engagement and wit--functions that are regulated by the frontal cortex--the same area that affects higher reasoning. Why is one considered a success while the other is considered a failure for doing the same thing?

The official clinical trail results for both Dimebon and Bapi were negative in regard to cognitive improvement, which was the major primary endpoint measured for both drugs. However, in the case of Bapi, post-hoc stratification of APOE4-positive versus APOE4-negative patients showed that the latter group had some benefit. So, in the ongoing Bapi trial, I believe they included the APOE4 stratification as a primary endpoint and there could again be a positive result. The major caveat is that in the first trial and beginning of the current trial, APOE4-positive patients also suffered from more adverse side effects, including vasogenic edema (inflammation) of the brain and in some cases cerebal micro-hemorrhage. So the dose of Bapi in the ongoing trial had to be lowered for the APOE4-positive patients. We will have to wait and see if Bapi still has benefits for Cognition. Let’s hope so.

Note from Cure Alzheimer’s Fund: For more info check out “The Success Stories of Tomorrow” and “Why Don’t the Drugs Work”

From Twitter:

1.@CureAlzheimers How are Alzheimer's and Chronic Traumatic Encephalopathy different?

They are entirely different. However, any brain trauma can theoretically increase downstream risk for AD. I don’t know of any data specifically linking chronic traumatic encephalopathy to AD.

2.@CureAlzheimers Opinions on the action on the alpha-7 nAch receptor in Alzheimer’s?

These drugs have strong potential for cognitive enhancement, perhaps even beyond that of current drugs on the market and maybe even working well in concert with each other. However, they would most likely just be treating the symptoms rather than the actual disease. We would certainly welcome their appearance!

Thank you again for attending our webinar! To stay up-to-date on our work, follow us on twitter at twitter.com/curealzheimers or like us on facebook at facebook.com/curealzheimers

Slides from the Webinar

Thank you to those who attended our Webinar on July 22 titled “Working Toward a Cure for Alzheimer’s: Clues from our Genes”. Below are the slides from the event. Video clips addressing key components of the presentation and blog posts responding to questions from the webinar will be posted shortly.

Click each slide to advance.

Brain Scan Diagnostics for early detection of Alzheimer’s --- a good idea?

There is debate about this.  A panel of leading Alzheimer’s researchers has recommended new guidelines for earlier diagnosis of Alzheimer’s Disease (AD), including the use of brain imaging.  While most commentators have hailed this news, a few have raised concerns. One of the clearer expositions of this was a Forbes online blog by Robert Langreth on July 15 entitled “A Scary Idea: Pre-emptive Brain Scans for Alzheimer’s.”

Langreth hypothesizes this diagnostic report:
“You feel fine and have no symptoms, but your brain is slowly rotting away. And there is nothing we can do about it.” Maybe he should have added “now”.

What is behind all this, and is this proposal really useful for patients and research?

"CAF's Sam Gandy delivers "Hot Topics" session at International Conference on Alzheimer's Disease (ICAD)"

At ICAD 2010 in Hawaii Dr. Sam Gandy of Cure Alzheimer's Research Consortium presented the results of a study showing a new class of biomarkers that can stick to protein structures in the body and emit colors reflecting the different shapes or forms of the proteins. They are called luminescent conjugated oligothiophenes (LCOs) or luminescent conjugated polymers (LCPs). Among other uses, they are currently being employed in test tubes, animal models and autopsied Alzheimer’s brains to study the structure of protein deposits caused by the disease. The new markers bind to the two well-established hallmarks of Alzheimer’s – beta amyloid plaques and tau tangles – and glow different colors depending on which forms of the deposits they “stick” to (e.g., plaques often “glow” orange, while tangles glow yellowish green).

Webinar on July 22: "Working Toward a Cure for Alzheimer's: Clues from our Genes" with Doctor Rudy Tanzi

Join us for our 2nd annual webinar on June 22. We will be hosting Dr. Rudy Tanzi, who will present his latest findings in the field of Alzheimer’s disease genetic research. The presentation will include a brief history of Alzheimer’s disease research, an explanation of the Alzheimer’s Genome Project, as well as the introduction of his new research on abeta as an anti-microbial agent.

Click HERE to register.

If you are unable to attend the webinar, e-mail us at info@curealz.org and we will send you a podcast of the event.

Dr. Rudy Tanzi is the Joseph P. and Rose F. Kennedy Professor of Neurology at the Harvard Medical School and the Director of the Genetics and Aging Research Unit at Massachusetts General Hospital. He has been investigating neurodegenerative disease since 1980 when he participated in the pioneering study that led to the location of the Huntington disease gene. He has identified several Alzheimer’s disease genes, including the first Alzheimer’s gene, the beta-amyloid protein precursor (APP). His work in the Alzheimer’s Genome Project, which has identified other new Alzheimer’s genes, was recognized by TIME magazine as one of the top 10 medical breakthroughs of 2008. Dr. Tanzi is a world-renowned leader in the studies of Alzheimer’s disease genetics.

The event will be held online, with each participant connecting through their own computer and telephone. More information on the webinar process can be found at www.gotowebinar.com

If you have any further questions, please contact us Katie Cutler at kcutler@curealz.org

McCance presents at Venture Summit East 2010

Henry McCance, Cure Alzheimer’s Fund co-founder and chairman emeritus, Greylock Partners, was a keynote speaker at Venture Summit East 2010. This two-day gathering highlighted the significant economic, political and technology trends impacting the global growth investor and was held at Harvard Business School. Venture Summit East features the most influential institutional investors, venture capitalists, corporate buyers, investment bankers and research analysts in the eastern United States in keynote presentations and panel debates.

Henry’s presentation featured ideas about how to use a venture capital approach to solve world problems. He focused on Alzheimer’s, citing the scope of the problem and Cure Alzheimer’s Fund’s innovative and targeted approach to end the disease.

Peek and Treat: A Pioneering Collaborative Research Project

Despite advances in understanding the pathology of Alzheimer’s disease, advancements in its diagnosis and treatment are limited. To address this key need, researchers at the University of Texas Health Science Center at Houston (UTHealth) and the University of Houston(UH) have been awarded a $150,000 grant from Cure Alzheimer’s Fund to pursue innovative work.

Tjan highlights venture capital approach to research

Tony Tjan, a member of our advisory board, recently wrote a blog post on the innovative field of medical research entrepreneurship. He highlights our effort to take a venture capital approach in order to improve what is currently a broken research system.

The medical research model as we know it today is broken. Why? Three words: insufficient, inefficient, and ineffective. This is both the big problem and the big opportunity for medical entrepreneurship. Today's model is insufficient because typically 1% or less of the amount spent each year on diseases goes towards cure research, with the balance going to caring for people with the disease. Alzheimer's, for example, costs our country hundreds of millions of dollars each year, yet we spend just one cent out of every $4.00 available towards a cure.

You can read the rest of this article, and other posts on the topic of entrepreneurship, at his Harvard Business Review Blog.

Economist agrees we need to invest in research!

The prestigious Economist weighs in on the “pooling of drug test data” discussion (Wall Street Journal, “Drug Makers Will Share Data From Failed Alzheimer’s Trials”, June 11, 2010) and agrees with Cure Alzheimer’s Fund: the emphasis should be on research that finds the cause of the disease rather than spending billions on the development of drugs that may be addressing the wrong targets or the right targets in the wrong ways. To quote the Economist, “the problem of what causes Alzheimer’s is profound” and so far, unresolved. In fact, as the article points out, fundamental perspectives on the causes of the disease are changing right now, and to at least some extent obviating the billions spent on drugs developed from very imperfect information about the basic pathology of Alzheimer’s.

It is a very hard problem to solve, but, again as the Economist states, “it is the “R” rather than the “D” of research and development that needs to be emphasized at the moment.” We at CAF couldn’t agree more with the Economist’s conclusion that now is the worst time to be cutting back on the “R”, which, in fact, NIH is doing.  The numbers that are increasingly well known are staggering and depressing. The United States will spend roughly $170 billion on care for Alzheimer’s patients in 2010, but invest only about $480 million in research into the causes of the disease through the National Institutes of Health in 2011. Shockingly that number is DOWN from $643 million in 2006.

As the Economist summarizes, “you get what you pay for”. Unless we rebalance this equation of care spending to cure spending, the future for the roughly half of people over 85 who have the disease or will get it in the next ten years is bleak indeed.