Interview with an Alzheimer’s expert Part III: The genetic component

September 21, 2010 by  
Filed under . ANNOUNCEMENTS, ALZHEIMER'S

My mother died of pneumonia at the age of 76 but she suffered from dementia during the last 10 years of her life. Doctors thought she had Alzheimer’s disease (AD) but since no autopsy was ever performed, the diagnosis was never confirmed. I come from a family with no history of cancer or heart disease. But there is this possibility of AD that hangs over my head. Last week, we addressed several questions about AD to Dr. Michael Rafii of the Memory Disorders Clinic at UCSD Perlman Ambulatory Care Center in La Jolla, California and of  the University of California, San Diego. Today, I bring you the last part of this Q & A.

Today, Sept 21 is World Alzheimer’s Day.

QUESTION: There is a genetic component to Alzheimer’s. Yet, genetic markers for Alzheimer’s have yet to be identified. What makes Alzheimer’s so complex that it is extremely difficult to find genetic and biomarkers and treatment for the disease?

ANSWER:

AD is most likely due to a combination of genetic susceptibility and environmental influence. Early-onset AD is a rare form of AD, affecting only about 5 percent of all people who have AD. It develops in people ages 30 to 60.

 Some cases of early-onset AD, called familial AD (FAD), are inherited. FAD is caused by a number of different gene mutations on chromosomes 21, 14, and 1, and each of these mutations causes abnormal proteins to be formed. Mutations on chromosome 21 cause the formation of abnormal amyloid precursor protein (APP). A mutation on chromosome 14 causes abnormal presenilin 1 to be made, and a mutation on chromosome 1 leads to abnormal presenilin 2.

Even if only one of these mutated genes is inherited from a parent, the person will almost always develop early-onset AD. This inheritance pattern is referred to as “autosomal dominant” inheritance. In other words, offspring in the same generation have a 50/50 chance of developing FAD if one of their parents had it.

 Scientists know that each of these mutations causes an increased amount of the beta-amyloid protein to be formed. Beta-amyloid, a major component of AD plaques, is formed from the protein APP.

 These early-onset findings were critical because they showed that genetics were involved in AD, and they helped identify key players in the AD process. The studies also helped explain some of the variation in the age at which AD develops.

 Late-Onset AD

Most cases of Alzheimer’s are of the late-onset form, developing after age 60. Scientists studying the genetics of AD have found that the mutations seen in early-onset AD are not involved in this form of the disease.

 Although a specific gene has not been identified as the cause of late-onset AD, one predisposing genetic risk factor does appear to increase a person’s risk of developing the disease. This increased risk is related to the apolipoprotein E (APOE) gene found on chromosome 19. APOE contains the instructions needed to make a protein that helps carry cholesterol in the bloodstream. APOE comes in several different forms, or alleles. Three forms—APOE ε2, APOE ε3, and APOE ε4—occur most frequently.

 APOE ε2 is relatively rare and may provide some protection against the disease. If AD does occur in a person with this allele, it develops later in life than it would in someone with the APOE ε4 gene.

 APOE ε3 is the most common allele. Researchers think it plays a neutral role in AD—neither decreasing nor increasing risk.

 APOE ε4 occurs in about 40 percent of all people who develop late-onset AD and is present in about 25 to 30 percent of the population. People with AD are more likely to have an APOE ε4 allele than people who do not develop AD. However, many people with AD do not have an APOE ε4 allele.

 Dozens of studies have confirmed that the APOE ε4 allele increases the risk of developing AD, but how that happens is not yet understood. These studies also have helped explain some of the variation in the age at which AD develops, as people who inherit one or two APOE ε4 alleles tend to develop AD at an earlier age than those who do not have any. APOE ε4 is called a risk-factor gene because it increases a person’s risk of developing AD. However, inheriting an APOE ε4 allele does not mean that a person will definitely develop AD. Some people with one or two APOE ε4 alleles never get the disease, and others who develop AD do not have any APOE ε4 alleles.

Interview with an Alzheimer’s Expert Part II: To be tested or not to be tested

September 13, 2010 by  
Filed under ALZHEIMER'S

Today, we will continue with our Q & A on Alzheimer’s Disease (AD) with Dr. Michael Rafii and ask about tests for AD.

QUESTION: There are many experimental tests for Alzheimer’s but, there is no still no “gold standard” diagnostic procedure. Currently, the only confirmatory test is by autopsy. Do you think a standardized diagnostic test will be available soon?

ANSWER: Yes, I believe that some combination of amyloid imaging, volumetric MR I as well as cerebrospinal fluid analysis will be utilized for diagnosis of AD, before its symptoms become visible.  There will likely be a need for a screening test, before such a large, and expensive workup is ordered by physicians.

QUESTION: Recently, there was a report about a test that can to detect Alzheimer’s before the symptoms even start. How can this be possible? How can they diagnose a disease with symptoms?

ANSWER: [see above, e.g. referring to answers published in Part I last week]we now have tools such as cerebrospinal fluid analysis and neuroimaging that allow us to measure amyloid in the brain, and are helping us detect AD’s pathology before symptoms show up.

QUESTION: Given that there is no treatment in the horizon, if such a test that detects Alzheimer’s 10 years before it becomes symptomatic ever becomes available, would you recommend patients to get tested?

ANSWER: It is a personal choice.  Some patients are already deciding to get tested with current technology because of a strong family history, and have seen the burden that it places on caregivers.  They want to make financial and legal plans and perhaps make lifestyle changes as well.

QUESTION: If, at age 40, I tested positive for Alzheimer’s using this hypothetical test, are there ways to slow down or even stop the disease before it becomes symptomatic?

ANSWER:  The jury is still out on this.  There have been many studies showing certain types of diets, including the Mediterranean diet, regular physical exercise, and staying cognitively active, may all contribute to lowering the risk of developing AD.  This is an area of tremendous research activity.

About D r. Michael Rafii:

Dr. Michael Rafii, MD, PhD is the  co-director of the Memory Disorders Clinic at UCSD Perlman Ambulatory Care Center in La Jolla, California and Assistant Professor of Neurosciences at the University of California, San Diego. He is also the Associate Medical Core Director of the Alzheimer’s Disease Cooperative Study (ADCS) specializing in cognitive disorders, including dementias such as AD.

About ADCS:

The Alzheimer’s Disease Cooperative Study (ADCS) was formed in 1991 as a cooperative agreement between the National Institute on Aging (NIA) and the University of California San Diego. The ADCS is a major initiative for Alzheimer’s disease (AD) clinical studies in the Federal government, addressing treatments for both cognitive and behavioral symptoms. This is part of the NIA Neuroscience and Neuropsychology of Aging Program’s effort to facilitate the discovery, development and testing of new drugs for the treatment of AD and also is part of the Alzheimer’s Disease Prevention Initiative.

Interview with an Alzheimer’s expert, Part I: How far are we from a treatment?

September 9, 2010 by  
Filed under ALZHEIMER'S

5.3 million Americans have AD and 1 person every 70 seconds is diagnosed with the disease. There are many questions that need to be addressed regarding this disease.

We are pleased here at Battling for Health to have an exclusive interview with one of world’s foremost experts on Alzheimer’s disease (AD).

Dr. Michael Rafii, MD, PhD is the  co-director of the Memory Disorders Clinic at UCSD Perlman Ambulatory Care Center in La Jolla, California and Assistant Professor of Neurosciences at the University of California, San Diego. He is also the Associate Medical Core Director of the Alzheimer’s Disease Cooperative Study (ADCS) specializing in cognitive disorders, including dementias such as AD.

We sent several questions on AD to Dr. Rafii and we are happy to share with you his responses.

QUESTION: AD has been the subject of numerous research studies but till now, no effective treatment has been found. Why is it so difficult to find a treatment for this disease? How far are we from a treatment?

 ANSWER: Current research indicates that AD may in fact be silently developing in the brain over 10-20 years, BEFORE its key symptom of short term memory loss even shows up in patients.  The idea is that a protein called beta-amyloid is slowly accumulating in the brain, first damaging brain cells, and then depositing into plaques.  Many drugs, some of which target amyloid, have been tested in the symptomatic phase, which is likely too late in the course of the disease to have a tremendous impact.  However, we now have tools such as cerebrospinal fluid analysis and neuroimaging that allow us to measure amyloid in the brain, and are helping us detect AD’s pathology before symptoms show up.

 I think a good analogy for AD is heart diease.  If a patient presents with a Heart Attack, starting them on a cholesterol lowering medication at that time will be a little too late.  Rather, if they start lowering their cholesterol years earlier, they may never have the heart attack in the first place.  Some believe that amyloid is analogous to cholesterol.  The challenge is to measure the amyloid and to get drugs that lower amyloid INSIDE the brain.  By lowering amyloid levels, we might lower the risk of having symptomatic AD, that is memory loss and dementia.

 We currently have trials in progress for medications that are being evaluated in the mildest stage of AD, when memory loss is just starting to occur.  I am optimistic that in the next few years we will have new treatments available.

Medical research such those being conducted at Dr. Rafii’s clinic will hopefully bring AD treatment closer to reality. However, in order for research studies t be conducted, research subjects and volunteers are needed. Check out how you can help at: www.adcs.org/Studies/ImagineADNI.aspx.

 Follow Alzheimer’s Research on Facebook: www.facebook.com/pages/Alzheimers-Disease-Research/114211355284888

We have many more Q & A on AD with Dr. Rafii which we will share with you in the coming posts. Stay tuned!

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