Disease Focus Series: a big week of exciting progress on Alzheimer’s Disease

UPDATE: I have added more discussion at the bottom about therapeutics and how regenerative medicine might work for AD.

Alzheimer’s Disease (AD) is the most common cause of dementia throughout the world, affecting 10s of millions of people. The cost to society is staggering and on a personal level for those of us who have had relatives with the disease, the personal fallout is just as enormous.  The last week has seen some very exciting news about research into AD giving more reason for hope about future treatments.

Given the tremendous negative impact of AD on humanity and its degenerative nature, it is a logical and very important disease target for regenerative medicine therapy. One of the hurdles with AD is that at the time of diagnosis, AD has already often wreaked havoc on the brain and done severe damage. Our brains are so powerful and flexible in function that they frequently can mask symptoms even under conditions of severe damage. The concern is that some of the damage from AD is likely irreversible.

Seven years ago, NIH and other groups came together to start a collaborative research program to identify AD markers.  The NY Times reported a few days ago on some initial leads from this effort. Because of the large number of scientists studying AD throughout the world and the equally large number of studies on AD that are ongoing, any kind of coordinated collaborative efforts are bound to bear fruit that will help in the diagnosis and treatment of AD. The aforementioned effort, the Alzheimer’s Disease Neuroimaging Initiative (ADNI) is a great example of this.

Early, pre-symptomatic diagnosis of AD is crucial so that it can potentially be treated or hopefully cured prior to significant damage.

In addition to imaging, scientists have been working diligently to find a blood or spinal fluid test that would predict AD. Because imaging is a very involved, costly process, it is not amenable to large scale screening of the at risk population. But a blood or spinal fluid test would be.  Such a test is becoming a reality. Researchers in Belgium have reported in the Archives of Neurology their study on a spinal fluid test that predicts AD with great accuracy.  Remarkably, more than 1/3 of patients with no apparent cognitive symptoms had the AD “Signature” in their spinal fluid, putting them at high risk of developing the disease in the future.

What this means is that most or nearly all AD patients likely in essence have the disease for decades before it become clearly clinically apparent. As a result, the window to treat the disease may be very long. What we need now are treatments to stall or prevent the disease before significant damage is done. Stem cell based therapies are just one potential approach to treating AD.

The ability to identify people at high risk for AD before they are sick also may allow researchers to pinpoint the very earliest events in AD and their causes! However, until effective treatments are developed, I personally would not be in favor of widespread screening of the population for the AD signature.

What about treatments or prevention? There is a lot in the pipeline coming that has potential, but very little available. A few months ago Baxter announced some promising results for AD on its drug GAMMAGARD, now used for other conditions.  It appeared to slow the progress of AD. Other companies such as Wyeth (bapineuzumab) are also working on drugs. And of course there are approved drugs for treating the symptoms of AD that show some albeit very modest beneficial effects.

What we need are treatments to prevent AD or reverse it.

How might a stem cell-based regenerative medicine advance treatments for AD?

One approach being explored is to use adult stem cells such as bone marrow MSC’s to deliver treatments (maybe something such as shRNA…but against what?) to the sites of damage or to mediate immune changes that are beneficial. Neural stem cells might also function to deliver treatments as well.

Another possibility is cell replacement using neural progenitors generated from hESC.

Similarly, the notion of using neural stem cells is also being considered for cell replacement.

Stem cells are also being used as models to try to understand the etiology of AD better.

You can learn more about CIRM funding for AD research here (near the bottom of the page).

One of the challenges of treating AD is the complexity of the human brain. Unlike most organ systems the brain normally has few stem cells because any kind of cell growth in the brain (much the same as any therapeutic cell replacement) could have profoundly negative consequences for cognitive function and memory. As a result, any kind of cell replacement therapy would not restore the incredibly complex structures present prior to the damage from AD and likely could not bring back memories.

Also without understanding and targeting the molecular events that cause AD, any new brain structures produced by cell therapy would be subject to being damaged by AD as well unless somehow they were made immune.

I think the key to AD treatment and prevention is a better understanding of why it happens in the first place.  Stem cell based models are likely to be extremely helpful in this regard.


  1. My mother and her mother and sister died with bad Ad. I am now starting to go that way too and want to go for stem cell transplant. My need is to know who are the best people to go to and what the cost is for doing it.

  2. What do you see as the role for iPS cells here? We have known for years that disease has pre-clinical markers pre-dating clinical diagnosis sometimes by decades. I would hope that studying the pre-clinical environment at a celluar and genomic level would lead to better understanding of the disease and more targeted effective interventions

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