Quick Search For Posts On The Following Topics:

Thursday, October 20, 2011

Could Hypertension Drugs Help People With Alzheimer's? FTD?

So, since I have been taking an ACE Inhibiter for a few years, specifically Enalapril, this article was particularly interesting. Though I take a sub-clinical 5mg dosage as a prophylactic to protect my kidneys from the ravages of Type II Diabetes,  any extra benefits are just fine with me. I think the absolutely coolest thing about this whole class of drugs is that they are all originally synthesized from compounds found in pit viper venom, they inhibit angiotensin-converting enzyme (ACE), a component of the blood pressure-regulating renin-angiotensin system. This article is about Alzheimer's Disease, but may certainly have other implications.

Science Daily (Oct. 17, 2011) — Within the next 20 years it is expected the number of people with Alzheimer's disease (AD) will double from its current figure of half a million to one million. A new study has looked at whether certain types of drugs used to treat high blood pressure, also called hypertension, might have beneficial effects in reducing the number of new cases of Alzheimer's disease each year.

The team of researchers from the University of Bristol have looked at whether drugs already being used to treat hypertension, particularly ones that specifically reduce the activity of a biochemical pathway, called the renin angiotensin system, might reduce the occurrence of Alzheimer's and another common type of dementia called vascular dementia.

The study, conducted with the support from North Bristol NHS Trust and published online in the Journal of Alzheimer's Disease, stems from work by one of the team's members, Dr Patrick Kehoe. Dr Kehoe, who is a Reader in Translational Dementia Research and co-leads the Dementia Research Group at Frenchay Hospital, Bristol, is a leading authority on the possible role of the renin angiotensin system in Alzheimer's.
This pathway is very important in blood pressure regulation and, for at least a decade, links between hypertension and dementia have been known but poorly understood.

In more recent years it has been shown that certain signals produced by this pathway contribute to a number of the damaging effects often seen in the brains of people with Alzheimer's. These include memory loss, lowered blood circulation in the brain, higher levels of brain inflammation and increased levels of brain cell death due to reduced oxygen circulation.

Dr Patrick Kehoe said: "Drugs that can prevent Alzheimer's occurring at all, or delaying its onset would have a substantial benefit on the lives of future sufferers, their families, as well as an overstretched health care system.

"Current Alzheimer's drugs treat memory loss by attempting to correct chemical imbalances in the brain but these only work for a limited time. This limited treatment period is because the drugs are unable to stop the underlying mechanisms that cause the disease. Therefore the need to find new ways of stopping Alzheimer's goes on."

Dr Kehoe's research led him to experts in the study of risk factors for disease in large populations and datasets. Professors Richard Martin and Yoav Ben-Shlomo, and researcher Neil Davies in the University's School of Social and Community Medicine, used the General Practice Research Database, which holds anonymised data on approximately ten million people who attend General Practitioner surgeries around the UK. The research team made some very interesting observations in what is one of the largest studies of its kind on dementia in the UK.

The researchers found people over 60 years, who had ever taken one of two different groups of drugs that target the renin angiotensin system in the previous ten years, had a 50 per cent lower risk of developing Alzheimer's with a more modest 25 per cent reduced risk for forms of vascular dementia compared to patients on any other types of hypertension drugs. This suggests that these benefits, if truly causal, are not merely due to a blood pressure lowering effect and may involve specific biochemical alterations.
Professor Richard Martin added: "Whilst our findings are interesting, these are not conclusive findings. We now need to do the clinical trials to properly test our observations."

Dr Kehoe and colleagues are now currently in the process of trying to obtain funding to undertake this necessary further research. If found to be successful, these treatments could be relatively quickly entered into Alzheimer's care since these drugs are already used for other conditions and are thought to have reasonably low side effect issues.

Friday, October 14, 2011

Could Alzheimer's Dementia Be Caused by a Virus?

The following is an article from Psychology Today, and is closely related to the concept of dementias being contagious or transmissible. I would not be at all surprised if in the future some pathogen were linked to all of the tauopathies, but for now it is just speculation. Nothing more than something to make you say, "Hmmmm!"


Could Alzheimer's Dementia Be Caused by a Virus?

Evidence links several common infections to the development of dementia.
Alzheimer's Disease is a slowly progressive illness of neuron loss leading to memory problems, cognitive impairment, and eventually death.   Since there appear to be no conventional medicine ways to prevent Alzheimer's and there is no known cure, there is a flurry of research trying to figure out what may cause the condition (besides genetics, which we can't do much about) and what might help the symptoms.
Today, we will take a peek at one of the more compelling theories about the cause of Alzheimer's -- it may well be due to an infection. Meaning exposure to certain parasites, bacteria, or viruses, particularly those that tend to inhabit the central nervous system, could bring on the disease. Even if you don't find Alzheimer's that compelling, if infectious agents contribute to its pathology, then you have to open your mind to the idea that many neurodegenerative processes could be due to (or accelerated by) infection.  Neurodegenerative diseases include many neurological illnesses, but also depression, bipolar disorder, schizophrenia, autism, and some other psychiatric illness.

What is the argument against infection as an ongoing contributing factor?  Well, where's the bug? Do a spinal tap - does the fluid grow any bacteria in culture?  Are there white blood cells (sign of active infection)?  Is there an elevated level of protein (a sign of viral infection)?  Over the last hundred years we've become pretty good at finding bugs.  It's hard to imagine them hiding from us, even in the protected environment of the human skull.  So if you bring up the idea of infections causing Alzheimer's disease to a physician friend and he or she scoffs at you -- that's why.  Where's the bug?
With that in mind, let's plunge forward into a very good review by Urosevic and Martins from the Journal of Alzheimer's Disease, "Infection and Alzheimer's Disease: The Apoe epsilon4 Connection and Lipid Metabolism."

The whole theory is based on the following premise: there's a continuous, chronic infection supplying persistent live microorganisms, and their toxic products stimulate the host's (that's you) inflammatory response.  The pathogen itself damages the neurons, and the brain's inflammatory response also damages the neurons.

ApoE4 is the  Alzheimer's vulnerable genetic variant of apolipoprotein. ApolipoproteinE is basically a molecular key that helps cholesterol and triglycerides go from the circulation into the brain. Since we know that being a carrier of ApoE4 makes one more likely to get Alzheimer's, any theory postulating an infectious origin of Alzheimer's will have to explain why ApoE4 will leave more vulnerable as well. Fortunately, the infectious theory meets that criteria, as you will see below.

What infectious agents are we talking?  Some viruses immediately come to mind, specifically herpes viruses.  These little guys are exceedingly common and come in lots of different flavors, and are well known to hide out in nerve cells for the duration of the host's life (an easy example of "There's the bug.")  HSVI, associated with cold sores, infects people early in life and hangs out in the trigeminal ganglia (the nerve root of the trigeminal nerve that innervates a good part of the face).  Some people get cold sores, some people don't, but those who do are more likely to be ApoE4 carriers.  People infected with HSVI are also more likely to develop Alzheimer's.  ApoE4 mice were more likely to carry invasive HSVI and have brain colonization of the virus.
Other viruses implicated include human herpes virus 6 (cause of roseola, a common childhood illness of high fever followed by a characteristic rash), HIV, hepatitis C, and cytomegalovirus (a cause of mononucleosis-like illness and fatigue symptoms).  It is well known that HIV causes a form of AIDS dementia (which happens to be more common in carriers of ApoE4), so it would make sense that other common viruses that infiltrate the neurons might lead to other types of dementia.

All the common inflammation players (TNFalpha, IL-6, nitric oxide synthase) are involved in fighting off viral infections.  We know these players have a role in Alzheimer's pathology and in depression and bipolar disorder.  Interestingly, as we get older, our immune response becomes less aggressive, and it is perhaps then that the infectious agents hold sway, leading to Alzheimer's pathology.  Other inflammation-mediated brain disease occurs at different developmental stages - late adolescence and early adulthood for schizophrenia, and infancy for autism.

In this very recent study of mice, scientists were able to inject the extracts of mouse brains from mice with Alzheimer's (or an experimental mouse version of it) into mice with no signs of Alzheimer's Over time, the injected mice began to develop plaques and mouse dementia, while mice that weren't injected didn't develop the problem.

There are also suspected bacterial causes.  The "spirochetes" are a type of sneaky bacteria that are known to infect nerves (as in syphillis and Lyme disease).  Some spirochetes that cause gum disease are found in the mouths of Alzheimer's patients and healthy folks, but in the Alzheimer's patients, they are found in the brain more often than in healthy folks.  Certain spirochetes have been found in the amyloid plaques in the brains of patients with Alzheimer's (once again - there's the bug).

Chlamydia pneumoniae is an intracellular bacterial pathogen also implicated in Alzheimer's dementia.  Not surprisingly, it is better known as a common cause of pneumonia and other acute respiratory infections, but infected immune cells could presumably carry Chlamydia pneumoniae from the upper respiratory tract to the brain if the blood brain carrier is compromised in some fashion.  Chlamydia pneumoniae has been injected into mouse brains and causes amyloid deposits, which anyone will agree is suspicious behavior.  Once again, ApoE4 comes up, as ApoE4 seems to allow for greater bacterial load and numbers of infected cells.

ApoE4 is not only a bad guy when it comes to Alzheimer's in the modern world.  Carriers are at greater risk of atherosclerosis, stroke, and poor recovery from head injury.  And ApoE's role as a molecular marker and director of where lipoproteins go is key.  Lipoproteins are how fat and antioxidants are carried throughout the body.  It is probably not a coincidence that major conditions leading to weight loss without any particular effort are infectious disease and Alzheimer's (along with cancer and melancholic depression).   ApoE4 in particular is associated with poor clearance and recycling of lipoprotein particles.  It's just not a very efficient key.  If everything is going along just fine, maybe we don't need a particularly efficient key.  Add stress or infection, though, and you have a greater need for metabolic efficiency.  If you fall behind on cleanup and recycling, garbage builds up in the brain, causing major problems.

Wednesday, October 5, 2011

Alzheimer's Might Be Transmissible - Or It May Not Be!

The following story from Science Daily is being reported by nearly every news service.  I am very skeptical for several reasons. First, and foremost, caregivers don't seem to have an abnormally higher risk of developing the disease. Second - they actually transplanted brain tissue. That is akin to transplanting a tumor, and saying cancer is contagious ...oh Wait! Some forms of cancer do seem to be contagious. Hmmm... In any case hopefully it will shed some light on the process, and maybe open some new research pathways into the tauopathies. Here is the whole article:

Alzheimer's Might Be Transmissible in Similar Way as Infectious Prion Diseases, Research Suggests

ScienceDaily (Oct. 4, 2011) — The brain damage that characterizes Alzheimer's disease may originate in a form similar to that of infectious prion diseases such as bovine spongiform encephalopathy (mad cow) and Creutzfeldt-Jakob, according to newly published research by The University of Texas Health Science Center at Houston (UTHealth).

"Our findings open the possibility that some of the sporadic Alzheimer's cases may arise from an infectious process, which occurs with other neurological diseases such as mad cow and its human form, Creutzfeldt-Jakob disease," said Claudio Soto, Ph.D., professor of neurology at The University of Texas Medical School at Houston, part of UTHealth. "The underlying mechanism of Alzheimer's disease is very similar to the prion diseases. It involves a normal protein that becomes misshapen and is able to spread by transforming good proteins to bad ones. The bad proteins accumulate in the brain, forming plaque deposits that are believed to kill neuron cells in Alzheimer's."

The results showing a potentially infectious spreading of Alzheimer's disease in animal models were published in the Oct. 4, 2011 online issue of Molecular Psychiatry, part of the Nature Publishing Group. The research was funded by The George P. and Cynthia W. Mitchell Center for Research in Alzheimer's Disease and Related Brain Disorders at UTHealth.

Alzheimer's disease is a form of progressive dementia that affects memory, thinking and behavior. Of the estimated 5.4 million cases of Alzheimer's in the United States, 90 percent are sporadic. The plaques caused by misshapen aggregates of beta amyloid protein, along with twisted fibers of the protein tau, are the two major hallmarks associated with the disease. Alzheimer's is the sixth leading cause of death in the United States, according to the Alzheimer's Association.

Researchers injected the brain tissue of a confirmed Alzheimer's patient into mice and compared the results to those from injected tissue of a control without the disease. None of the mice injected with the control showed signs of Alzheimer's, whereas all of those injected with Alzheimer's brain extracts developed plaques and other brain alterations typical of the disease.

"We took a normal mouse model that spontaneously does not develop any brain damage and injected a small amount of Alzheimer's human brain tissue into the animal's brain," said Soto, who is director of the Mitchell Center. "The mouse developed Alzheimer's over time and it spread to other portions of the brain. We are currently working on whether disease transmission can happen in real life under more natural routes of exposure."

UTHealth co-authors of the paper are Rodrigo Morales, Ph.D, postdoctoral fellow, and Claudia Duran-Aniotz, research assistant. Other co-authors are Joaquin Castilla, Ph.D., Basque Foundation for Science, Bilbao, Spain; and Lisbell D. Estrada, Ph.D., Universidad Catolica de Chile, Santiago, Chile. Duran-Anoitz is also a doctoral student at the Universidad de los Andes in Santiago, Chile. Soto, Morales, Castilla and Estrada did a portion of the research at The University of Texas Medical Branch at Galveston.

Comments are welcome.

Monday, October 3, 2011

Frontotemporal Degeneration: Rare Brain Disorder Is Highly Hereditary

Frontotemporal Degeneration: Rare Brain Disorder Is Highly Hereditary

ScienceDaily (Nov. 4, 2009) — New research shows that a rare brain disorder that causes early dementia is highly hereditary. The study is published in the November 3, 2009, issue of Neurology®, the medical journal of the American Academy of Neurology.

The brain disorder, called frontotemporal dementia, is formerly known as Pick's disease and destroys parts of the brain, leading to dementia, including problems with language or changes in behavior and personality. The disease often affects people under the age of 65.

"Knowing your family's health history may be one way for people to better predict their risk of developing dementia," said study author Jonathan Rohrer, MRCP Clinical Research Fellow at the Dementia Research Center at the University College London in the United Kingdom.

For the study, blood was drawn from 225 people who were diagnosed with frontotemporal dementia. The people were asked about family history of dementia and given a score of one through four. A score of one represents a person who had at least three relatives with dementia and an autosomal dominant inheritance, meaning that an affected person has one mutant gene and one normal gene and has a 50-percent chance of passing the mutant gene and therefore the disorder on to their offspring. A score of four represents a person with no family history of dementia.

The study found that nearly 42 percent of participants scored between a one and a 3.5, meaning they had some family history of dementia. However, only 10 percent had an autosomal dominant gene history.

The people in the study also had their DNA tested for five gene mutations thought to cause frontotemporal dementia. Mutations were found in two of the five genes.

"Many people were still found to have a strong family history of dementia even without having any of the five known gene mutations, suggesting that there are still unknown genes that cause frontotemporal dementia," said Rohrer.

"Discovering new genes and gene mutations could provide another key to unlocking the doors to new treatments and prevention strategies for dementia."

The study also found that behavioral problems associated with frontotemporal dementia were the most likely to be hereditary, while language problems were the least likely to be hereditary.

The study is supported by the United Kingdom Department of Health's NIHR Biomedical Research Centers, the Medical Research Council UK and the Alzheimer's Research Trust in the United Kingdom.

Comments are welcome.