April 27 2023
Posted May 17, 2012
On Oct. 10, leading researchers from the Cure Alzheimer’s Fund Research Consortium, including Steve Wagner, Ph.D., Sangram S. Sisodia, Ph.D., and Chairman Rudy Tanzi, Ph.D., gathered in Boston to discuss the road map to therapies.
David Shenk, author of the national bestseller The Forgetting, Alzheimer’s: Portrait of an Epidemic, moderated the event and questions were encouraged from the audience. Those questions covered various health and lifestyle issues, as well as the current state of research and the direction in which it is headed, and the facts about Cure Alzheimer’s Fund.
Posted Below Are Audience Questions, Answered by our Panel:
What are the early signs of Alzheimer’s vs. normal memory loss in the over 60’ish age group?
Virtually everyone experiences some subtle memory troubles as they get older. Alzheimer’s can start out very subtle indeed, but it will progress over time to be a serious problem. The classic distinction with Alzheimer’s is that some of the very earliest symptoms are difficulty in forming new memories — what will appear to be short-term memory trouble. That’s because the disease starts very close to the hippocampus, the part of the brain that forms new memories. Other early signs can be place confusion, difficulty with words, and trouble with basic math.
Do people with auto-immune disease have a higher incidence of Alzheimer’s disease?
No, not too our knowledge
Is there evidence that anesthesia has a causative relationship to AD?
We have shown that that the general inhalant anesthetic can accelerate Alzheimer’s plaques. As such, we personally recommend using desflurane instead. However, there is not yet enough data to suggest isoflurane should not be used any longer in the OR.
Does a family history of stroke or other vascular problems have any influence on a person getting Alzheimer’s?
Yes. Alzheimer’s risk is closely connected to cardiac and vascular health. Insults to the brain brought on by neurovascular disease and stoke can trigger and accelerate AD.
Must the exercise be quick-pace aerobic – is walking enough?
Walking is much better than sitting. But aerobic exercise is better.
What amount of exercise is needed to have an impact?
3-6 hours per week is recommended.
What does an enriched environment look like for a person who is already active? Does the level of activity or diversity of activity matter?
Coming to events like the Cure Alzheimer’s Fund symposium. Reading David Schenk’s books. : )
What is the effect of red wine and how much is needed?
Red wine has been associated with decreased risk for AD when take in moderation—a glass per day.
Please discuss risk factors:
Heading a soccer ball
not good, especially when ball is wet
Eye drops to get the red out
Bone density pills
probably OK but don’t know
obviously bad but not AD—prion dementia (CJD) is different
bad no matter what
Does exercising the mind with mental exercises have the same effect as physical exercise?
No, they don’t have the same effect. Both are important in different ways.
Other than exercise, what can people with a family history of Alzheimer’s do to prevent the disease?
There is not yet any guaranteed prevention. Anything that contributes to cardiac/vascular health may also lower risks of Alzheimer’s. That includes a heart-healthy diet, maintaining healthy stress levels, and keeping tabs on blood pressure and cholesterol.
Are there long (who test positive for the disease) term studies with people that you put on, let’s say, vegan diets (to prevent inflammation) and a running program to see how prevention works? Any thoughts on meditation and mindfulness?
Meditation, like deep (slow wave) sleep, can potentially turn off the default network in the brain and this turns off amyloid beta production and helps consolidate long term memories.
Mindfulness means a more active brain and more stimulation of synapses, which means a healthier brain.
A vegan diet is healthy for heart and thus for brain.
Is there a relationship between obesity (diet) and Alzheimer’s?
Obesity in middle age does significantly increase a person’s chances of succumbing to dementia later in life.
Obesity is a risk factor for AD—again—what’s bad for heart is bad for brain.
Does nutrition matter?
Yes indeed. A heart-healthy diet will very likely reduce your chances of succumbing to dementia later in life.
The statistics show an inordinate number of cases in the U.S., apparently the case even if you control for age, globally. Why?
That’s not true. The number of cases in the U.S. accords with our aging population.
Can you explain your 5 year timeline for a treatment? That seems optimistic. FDA approval requires longer than that.
For our new drugs, gamma secretase modulators, which Steve Wagner talked about, they are at least 10 years off since they are not yet in clinic. For other drugs that Rudy Tanzi is working on, e.g. Prana’s PBT2, it could potentially be ready in 5 years since it has already been through phase 2 in clinical trials.
Has it been determined that Alzheimer’s is definitely a genetic disease?
The mechanisms of Alzheimer’s are certainly connected to a variety of genes, and researching these genes does help us learn more about how to defeat it. But that doesn’t mean that genes directly cause the disease. So far, only in rare cases do we see a single gene mutation singlehandedly cause Alzheimer’s to develop. Our Alzheimer’s Genome Project will ultimately show us how many cases involve subtle genetic variants that only influence one’s susceptibility versus single gene mutations that cause the disease by a particular age with certainty. For now, we just don’t know.
Rudy, why don’t you have Chromosome 21 in your genetic list – especially since a new trial recruiting 300 persons with Down syndrome was just announced?
The APP gene is on chromosome 21 and was on the list. We are actively working with Down Syndrome groups to get AD therapies into trials on these individuals.
What are your thoughts on intranasal insulin?
Not enough data yet to know. So far trials have been too small to predict success. We need to wait for larger and longer trials.
What are the genes involved in late-onset Alzheimer’s?
APOE is number one followed by ADAM10, CD33, ATXN1, CR1, CD2AP, BIN1, ABCA7, MS4A, and CLU.
Can a drug scavenge the free radicals?
Yes, anti-oxidants do this.
Is it hard to find people who are willing to be part of these studies?
Actually, AD trials fill up pretty fast these days.
How closely linked is the mechanism of Alzheimer’s disease with other neurological diseases and is there progress in other disease research that may help you in your work in treating Alzheimer’s?
Many neurodegenerative diseases all involve misfolded proteins that aggregate into brain pathology and lead to neuronal cell death – Parkinsons, Lou Gehrig’s, Huntingtons’ disease, frontotemporal lobe dementia, etc. We are exploring common mechanisms by which these abnormal protein aggregates kill neurons. For example, one observation that we and others are working on is that their interaction with copper and iron generates free radicals.
What is the blood-brain barrier?
The blood-brain barrier is a fine mesh filter that protects the brain from various substances in your body’s bloodstream. Plenty of things that are perfectly healthy in your ordinary bloodstream would be toxic to the brain. So the blood-brain barrier makes sure these items do not get through. As we devise drugs to target Alzheimer’s disease, getting them safely through the blood-brain barrier is one of the challenges.
Predictors available today? How accurate is family history? What tests are available?
We can predict some cases of early-onset familial AD but these represent less than 2% of all AD. For late-onset AD, we still need to find all the genetic risk factors, beyond APOE, to carry out reliable testing. This is one of the goals of our AGP. Family history is good indicator especially if onset is early <70 yrs. For early (pre-symptomatic) detection, amyloid imaging and biomarkers in the CSFm (phospho-tau) are being developed.
Is reducing amyloid with exercise really enough? Isn’t even a small amount of amyloid enough to create tangles? Will a reduction be enough or do we need elimination?
It is well-established that tangle pathology/tangles occur well after the development of amyloid pathology and this has been documented in mouse models. Thus, I would argue that amyloid clearance through exercise-mediated mechanisms will significantly attenuate tangle pathology. Extending this argument, I do not feel that small amounts of amyloid will promote tangle pathology.
Is the treatment for early onset different than the treatment for old-age Alzheimer’s?
The treatment is the same but we will have to treat early onset AD earlier in life once we have a disease modifying therapy.
What is the biggest obstacle to bring these great ideas to market for patients?
At the moment, the greatest obstacle is money. We are able to pursue but a small fraction of our leads because of limited funds.
Is Alzheimer’s disease related in any way to prion disease/mad cow disease?
Both involve misfolded proteins and in both pathology spreads throughout brain. But entirely different proteins are involved in each. In AD, beta-amyloid and tau are involved and in prion disease, the prion protein is involved.
Has stem cell research regulation lifted under the current administration affected the trajectory of the Fund’s research? If so, how? And if not, what vision is there of their efficacy in the future?
Not much effect, actually. Stem cells are great tools for studying cause of AD but far away from being used therapeutically for treating AD.
Can you explain “vulnerable neurons” in the brain? What makes these neurons more vulnerable to AB assault than neurons in other areas? Exercise helps neuron growth only in the hippocampus in humans?
Paul Greengard, Nobel Laureate, is funded by Cure Alzheimer’s to study exactly this and is doing so in collaboration with Rudy Tanzi. They have already found a set of genes that influence vulnerability. The study is still in progress.
Neurogenesis only occurs in the hippocampus and corpus callosum of brain.
About Cure Alzheimer’s Fund
How does the Fund decide what research to support and allocate its monies?
Research decisions are made by the Research Consortium, our “dream team” of Alzheimer’s researchers who meet four times a year to review the state of the science and look for new leads. Our criterion is simple: we go where the science leads us, and fund only what the Consortium considers the very smartest proposals.
How often is funding of projects reviewed?
We consider new ideas constantly, and fund them rapidly, usually within a month, after they are approved.
What is the dollar amount needed to fund this research to get a result? $50M; $100M; 1B? Where should this funding come from?
Alzheimer’s disease is uniquely limited by a lack of funds, and there’s little doubt that we could get to a cure much faster if we had adequate funding. Hundreds of important studies and drug trials go unfunded every year. The federal government spends about $500 million annually on Alzheimer’s research. Private foundations like Cure Alzheimer’s Fund contribute millions on top of this. To move at top speed, the research community would require several additional billion dollars per year.
How does Cure Alzheimer’s coordinate efforts with other research efforts i.e. NIH, The Alzheimer’s Disease Genetics Consortium, and the National Cell Repository for Alzheimer’s Disease?
While none of these institutions take marching orders from another, coordination of efforts is effectively very close. Our Research Consortium keeps its finger on the pulse of all ongoing research and pursues only the research leads not yet being pursued by others.
How can we all help lobby congress or NIH or other large sources of funds to allocate more research dollars to this disease?
Call or write your congressional representatives. Better yet, seek them out in person.
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