The Tangled Neuron

The Emperor of All Maladies: Book Review

Dedicated scientists and suffering patients.  Passionate advocates and expert study groups.  Media reports of impending cures, calls for increased funding, and coordinated national efforts to fight disease.   

These are the ingredients of The Emperor of All Maladies: A Biography of Cancer.  In many ways, they are the ingredients of the Alzheimer’s story as well.

From The Financial Industry, A Gloomy View of Alzheimer's Research

There’s been a lot of optimistic headlines about diagnosing, treating and curing Alzheimer’s lately.  It seems some financial and industry analysts are not so optimistic. 

MarketWatch reports that the September issue of Neuroinvestment contains an extremely gloomy assessment of prospects for new Alzheimer’s drugs, and suggests that all research efforts need a “reset.”

Proteins, Aging and Alzheimer's

Summary:  In roundworms, hundreds of proteins form hard clumps as the animal ages.  This discovery may contribute to a better understanding of neurodegenerative diseases.

Much of the current research on neurodegenerative diseases focuses on a handful of proteins that tend to form hard clumps in the brain, including:

• beta amyloid in plaques associated with Alzheimer’s
• tau in tangles associated with Alzheimer’s
• alpha-synuclein in Lewy bodies associated with Parkinson’s and Lewy body dementia
• huntingtin associated with Huntington’s disease.

But small amounts of other clumped proteins have been found in Alzheimer’s plaques and tangles and in Lewy bodies.  Researchers in Cynthia Kenyon’s lab at the University of California, San Francisco wondered if those other proteins are just accidentally caught up in these clumps, or if they somehow contribute to neurodegeneration.


               Della David, Ph.D.

Dr. Kenyon’s lab focuses on the study of aging in a microscopic roundworm called C. elegans.  These roundworms are much simpler than humans or even mice.  In a series of experiments using C. elegans, the researchers found there are actually hundreds of proteins that form hard clumps as roundworms age.  “Our study shows that in worms, inherent protein aggregation is linked to the aging process,” says Della David, first author of the paper.

How Do Alzheimer's Disease and Vascular Dementia Interact?

Summary:   Researchers at The Rockefeller University have published a paper proposing a new model for how Alzheimer’s and vascular disease interact to worsen memory and thinking. If their theory is confirmed, medicines that block this interaction could someday be an important part of treatment for memory loss. 

Marta Cortes-Canteli, Ph.D.

In the last few years, many Alzheimer’s researchers have been working under the assumption that beta amyloid, the protein that makes up Alzheimer’s plaques, damages brain cells.  Other scientists, however, argue that Alzheimer’s is really due to blood vessel or vascular disease that reduces blood flow to brain cells.  Maybe both are right -- people with dementia tend to have multiple pathologies in their brains, and these pathologies seem to interact to increase the risk for and severity of dementia.

A new paper from researchers at The Rockefeller University suggests that a protein called fibrinogen might be involved in this interaction.  Postdoctoral fellow Marta Cortes-Canteli and her colleagues focused specifically on the role of fibrinogen and beta amyloid in the presence of abnormal blood clots and the cerebral amyloid angiopathy (CAA) my father’s autopsy showed.

Controversy over the Causes of Alzheimer's

Summary:  Dr. Rudy Castellani of the University of Maryland has received the 2010 Journal of Alzheimer’s Disease outstanding contribution award for his article criticizing the popular hypothesis that a protein called beta amyloid causes Alzheimer’s.  The award highlights the growing disagreement about the causes of Alzheimer’s.

Alzheimer’s is caused by plaques and tangles in the brain, right?  Wrong, says a group of researchers who believe that focusing on these abnormal proteins is keeping scientists from investigating other potential causes. 

In a 2009 article in the Journal of Alzheimer’s Disease, they wrote that the popular hypothesis that beta amyloid (the protein found in plaques) causes dementia is flawed. This flawed hypothesis is why potential Alzheimer’s drugs continue to fail in clinical trials, they said, and has caused unnecessary suffering for patients and families.

Rudy J. Castellani, Jr., MD

Last month, the 300+ Associate Editors of the Journal of Alzheimer’s Disease voted to give Dr. Rudy Castellani, the lead author of this article, the Journal’s annual award for outstanding contribution.  The award highlights the growing disagreement about the causes of Alzheimer’s.

Dr. Castellani is Professor of Pathology and Director of Neuropathology at the University of Maryland.  The two Editors-in-Chief of the journal, Mark Smith and George Perry, are co-authors of the paper, and with Dr. Castellani, have long hypothesized that events earlier in the disease process, not beta amyloid, cause Alzheimer’s.   Their logic goes something like this:

1. Abnormal accumulations of beta amyloid (the protein in plaques) and tau (the protein in tangles) are not harmful, and are simply end-stage signs of earlier problems
2. Recent research indicates that beta amyloid may be protective – a normal immune response and an anti-oxidant
3. The accumulation of beta amyloid that can be seen at autopsy (and on new brains scans) is not well correlated with dementia
4. The focus on these abnormal proteins has crowded out funding needed to research other hypotheses.

Amyloid in Alzheimer’s: Part of the Immune System?

Summary:  A new report from researchers at Massachusetts General Hospital suggests that the beta amyloid protein that makes up Alzheimer’s plaques might be part of a normal immune response.   If confirmed, this could explain how and why infection, brain injury, stroke and anesthesia are linked to increased risk of dementia.  This new model of how Alzheimer’s develops could also suggest new ways to prevent abnormal buildup of beta amyloid and treat or prevent dementia.

Researchers at Massachusetts General Hospital and their colleagues have reported that the beta amyloid protein that makes up Alzheimer’s plaques can reduce the growth of several  types of  bacteria and a yeast, all of which cause infections in the brain.

Alzheimer's Research: Starting Over?

This past Thursday, the University of Pennsylvania’s Institute on Aging presented “A Conversation on Breaking the Treatment Barrier: Moving from Disease Modification to Prevention of Alzheimer's Disease.”  Russell Katz, MD (Director, Division of Neurology Products, Food and Drug Administration) and Zaven Khachaturian, Ph.D. (President, Prevent Alzheimer’s Disease by 2020 Inc [PAD2020] and Senior Science Advisor, Alzheimer’s Association) gave presentations, followed by a question and answer period.

While headlines are still focused on curing Alzheimer’s, finding disease-modifying treatments and reducing amyloid in the brain, it seemed to me that the experts and the audience at this event had moved far beyond these topics.

MCI Symposium: Vascular Dementia and MCI, Part 1

        Vladimir Hachinski, MD, FRCPC, DSc

Dr. Vladimir Hachinski, a prominent stroke researcher, thinks that treating vascular diseases such as high blood pressure and “hardening of the arteries” can reduce your risk of both stroke and Alzheimer’s.  Several months after the 7th Annual Mild Cognitive Impairment Symposium, I’ve finally managed to report on Dr. Hachinski’s keynote speech at that event, and on his advice to people concerned about developing Alzheimer’s.

More Evidence Linking Sports-Related Head Injury to Memory Loss

Today's New York Times has a good article on brain injury and memory loss in a professional hockey player.

Surgery and Memory Loss Revisited

Judging by the comments on my previous post on surgery, anesthesia and memory loss, it's common to have cognitive problems after surgery.  But a new study by researchers at University of Washington in St. Louis shows that surgery does not necessarily lead to memory loss.

These results conflict with those of other studies, and more research is needed.

Family History of Alzheimer's and High Blood Pressure

Summary:   Middle-aged people whose parents were diagnosed with Alzheimer’s tend to have higher blood pressure and, at least in the lab, their blood produces more proteins that contribute to inflammation.  These characteristics may increase their risk of developing dementia.  Controlling high blood pressure in this group could lower their overall risk.

         Eric van Exel, MD, Ph.D.

A new study led by Eric van Exel at VU University Medical Center in Amsterdam compared characteristics of 206 middle-aged people whose parents were diagnosed with Alzheimer’s to those of 200 people of similar age whose parents were cognitively normal.As expected, more children with a parental history of Alzheimer’s carried the APOE4 genetic variation that increases the risk of dementia.  Independent from their APOE4 status, these children also had higher blood pressure and in the lab, their blood produced more of certain proteins that contribute to inflammation.

Mild Cognitive Impairment Symposium: What Do Autopsy Studies Tell Us?

        Joseph Parisi, MD

In a previous post, I wrote about donating your brain.  With brain donation, a patient can make a contribution to research, and the patient’s family typically receives a copy of the autopsy report at no charge. 

Autopsy studies using tissue from donated brains can help researchers understand the various changes in the brain that may underlie problems in memory and thinking.  These studies include examination of the brain by a neuropathologist, who evaluates the type and extent of brain pathologies, or abnormalities, that might be present. 

This kind of study was the focus of presentations by Dr. Joseph Parisi, Professor of Laboratory Medicine and Pathology at Mayo Clinic, and by Dr. Julie Schneider, Assistant Professor of Neurology and Neuropathology at Rush University Medical Center at the 7th Annual Mild Cognitive Impairment (MCI) Symposium last spring.  I’ve just posted a summary of their presentations on autopsy studies of the brains of people who had been diagnosed with MCI. 

CAA, Microbleeds and Dementia: A New In-Depth Report

In the three years since my father died, I’ve often felt like there’s been little progress in dementia research.  This week, I was reminded that the complexity of the topic sometimes hides the progress that has been made.

A good example of this is the research on the cerebral amyloid angiopathy (CAA) and microbleeds Dad had.  When he died, awareness about CAA and microbleeds was low, even among doctors.  Lately, though, I’ve been getting more emails from people whose family members have those conditions, and new research shows they are much more common than we thought.

Given the new interest in the topic, I thought I’d do a quick update.  I found so much new information that my quick update grew into a longer report (see CAA, Microbleeds and Dementia:  An Update). 

We still don’t know how to prevent or treat CAA or microbleeds – some of the new information brings more questions than answers.  But it’s still progress.

Head Injuries and Alzheimer's in Football Players

CNN has an interesting article today on the link between head injuries and Alzheimer's in [American] football players.  It makes you wonder how many cases of dementia could be prevented if we paid more attention to avoiding head injuries in the general population.

New NIA Progress Report on Alzheimer's Disease

When my father started to have problems with his memory, my understanding of Alzheimer’s was that it was a single and identifiable disease, and that we were close to finding a cure.  The 2007 version of the U.S. National Institute on Aging (NIA) Progress Report on Alzheimer’s Disease presents a more open-ended and nuanced view of memory loss.

Two Different Approaches to Alzheimer's Prevention (Part 2 of 3)

Jill Stein, MD

A new report published by Greater Boston Physicians for Social Responsibility and the Science and Environmental Health Network says environmental and lifestyle factors, not just genes, are major contributors to neurodegenerative diseases such as Alzheimer’s.  The report lists a broad range of ecological, health care, and lifestyle-related steps governments, communities and individuals can take to prevent Alzheimer’s and other diseases.   

In Part 2 of a Tangled Neuron series on prevention, one of the primary authors of this report, Jill Stein, MD, talks about the science behind the new report.

International Conference on Alzheimer's Disease (ICAD) 2008

Summary:  the majority of presentations at ICAD focused on Alzheimer's as a disease, and what we can do to cure it.  But the presentations on healthy brain aging (even in people with Alzheimer's plaques and tangles in their brains) were just as interesting.  From my layperson's point of view, we may learn as much from exploring healthy brain aging as we do from looking for an Alzheimer's cure.

It's hard to summarize ICAD 2008, held last week in Chicago.  The majority of the hundreds of oral presentations and thousands of poster presentations focused on molecular biology (genes, proteins, etc.), and on amyloid protein in particular.  But the three presentations in the plenary session on the last day highlighted that there are at least two ways to look at Alzheimer's: 

1. as a disease, with the focus on what can we do to cure it
2. as the opposite of successful aging, with the focus on what keeps our brains healthy as we age.

Paul Aisen, MD, now at University of California - San Diego, gave a presentation called "The Evolution of Alzheimer's Disease Clinical Trial Design."  His presentation was from the view of Alzheimer's as a disease, and what we can do to cure it.

Webcast: The Myth of Alzheimer's

If you want to congratulate Dr. Peter Whitehouse and Danny George for writing their book The Myth of Alzheimer’s, let them know how wrong you think they are, or are just plain curious, here’s your chance. They’ll be featured on a HealthTalk webcast tomorrow night (Wednesday, May 14th) at 7 PM eastern. Details are on the registration page at the HealthTalk site.

Alzheimer's Research at a Crossroads: a new conference report

Summary: A new conference report from the U.S. National Institute on Aging summarizes the presentations, discussions and recommendations of top Alzheimer’s researchers. From my layperson’s point of view, the report shows three reasons why Alzheimer’s research is at a crossroads:

1. We don’t really understand what causes memory loss and dementia.
2. Every brain is different, and multiple factors and diseases may underlie any one person’s memory problems.
3. Overall, research to date has not yielded the hoped-for answers.

Of the many recommendations made to the NIA, the ones involving broadening the concept of Alzheimer’s and collaborating with scientists in other fields make the most sense to me. The NIA meeting and report seem like good first steps towards consensus on which road to take.

Over the weekend, I’ve been reading through an excellent report on a conference on Alzheimer’s convened by the U.S. National Institute on Aging (NIA). The conference took place in October 2006, on the 100th anniversary of Dr. Alzheimer’s discovery of plaques and tangles in the brain of his patient Auguste D.

The Myth of Alzheimer's?

We seem to be rethinking everything right now - the energy we use, the pollution we create, the foods we eat. Peter Whitehouse, a prominent Alzheimer’s researcher and doctor, is also rethinking the disease we call late onset Alzheimer’s.

In his new book, The Myth of Alzheimer's: What You Aren't Being Told About Today's Most Dreaded Diagnosis, written with Danny George, Dr. Whitehouse questions just about everything we think we know about Alzheimer’s and memory loss. Their book comes at a time when I’ve started to rethink my late father’s dementia after two years of blogging about Alzheimer’s research.