Deciding whether to get tested for an Alzheimer's gene
Inherited forms of Alzheimer's disease are extremely rare, but for a small proportion of families who carry particular genes the results can be devastating. Luke Bishop talks to someone from an affected family.Liz Fox never really knew her father. When she was one year old he was diagnosed with early onset Alzheimer's disease and hospitalised. In 1981 at the age of 42 he died, when Liz was just four years of age.
In the family
Although Liz had always suspected there was Alzheimer's 'in the family', it was only when Tony was diagnosed with dementia that the gene mutation was identified as the cause. Liz admits that since his diagnosis she has been plagued with worries that she may also develop dementia.Liz says,
'After Tony was diagnosed with dementia and after testing he advised me that he has inherited the presenilin-1 gene. I wasn't that shocked as we had learnt from the family tree that dementia was in the family, although I was devastated for Tony, Jayne and their two sons.'She adds,
'However, when I started reading that there was a 50-50 chance of us getting the gene it started to torment me and I found myself thinking I had dementia, for example, when I'd forget my keys. When my husband talked about plans for holidays with friends I began thinking to myself that I don't need to listen as I won't know what's what anyway.'
Glimmer of hope
Because of her worries Liz decided to see a consultant at St Mary's Hospital in Manchester about possibly being tested for the gene. After speaking to the consultant, however, Liz decided not to go ahead with it, deciding that she would rather have the 'glimmer of hope' that she had not inherited the gene.She explains,
'Having a professional show you the high possibility that I could get this disease really scared me, but the thing she said to me was "What would you do if you got told you had it?" Once you have the knowledge there is nothing you can do to stop it, prevent it or take the knowledge of knowing you had it away.'However, she also says that if a cure or something that would slow the progression of the dementia were available then she would get the test done to see whether she carried the gene.
Genetic factors
In the meantime Liz remains very keen on raising awareness about inherited Alzheimer's and dementia in general. This October she will be taking part in research that aims to find a way to slow the progression of her rare type of dementia.There are three genes that, if inherited, lead to the development of early onset Alzheimer's disease. One is this mutated form of presenilin-1, and another is a mutation of presenilin-2. The third is a mutated version of a gene called APP.
All of these genes are related to the production of the protein amyloid, which builds up to form plaques in the brain during Alzheimer's and is thought to be a cause of the disease. Everybody has versions of these genes, but these particular mutations that lead to this inherited form of Alzheimer's disease exist in a small number of families.
Speaking about the risks of inherited Alzheimer's disease Jess Smith, Research Communications Officer, says,
'This is clearly an awful situation for Liz and her family and it shows the devastating impact these genes can have on the affected families. However, such examples are extremely rare and account for a very small proportion of cases of Alzheimer's disease. It's important to remember that most cases of early onset Alzheimer's disease are not the result of these genes.
'The majority of cases of dementia arise from a very complex variety of factors, of which genetics is just one. If you have a parent with dementia, your risk of developing the condition is only slightly higher. There are things that you can do to reduce your risk of developing dementia, such as taking regular exercise, eating a balanced diet and maintaining normal blood pressure and cholesterol levels.'
A diet high in cholesterol, fat and sugar may
influence the development of Alzheimer's disease in people who carry
the ApoE4 gene, a leading risk factor for the memory-erasing disease,
indicates a new USC study.
The study on mice, published June 12 in the journal eNeuro,
is the latest to explore the association between obesity and Alzheimer's
disease, both of which are associated with inflammation and both of
which affect millions of people.
For the study, researchers at the USC Davis School of Gerontology compared the effects of a poor diet on groups of mice that either had the Alzheimer's-associated ApoE4 gene or the relatively benign variant of the gene, ApoE3. After eating an unhealthy diet, the mice with the ApoE4 gene showed more Alzheimer's plaques -- a marker for inflammation -- in their brains, but those with ApoE3 did not.
"Part of what the results are saying is that risk doesn't affect everybody the same, and that's true for most risk factors," said Christian Pike, the lead author of the study and a professor for the USC Davis School of Gerontology. "Your genes have a big role in what happens to you, but so does your environment and your modifiable lifestyle factors. How much you exercise becomes important and what you eat becomes important."
Alzheimer's and obesity are among the intractable problems that USC researchers in multiple disciplines are seeking to unravel.
Both are widespread and costly. An estimated 5.4 million Americans have Alzheimer's, which costs an estimated $286 billion a year. The USC Schaeffer Center for Health Policy and Economics predicts the number of U.S. patients diagnosed with Alzheimer's will more than double to 9.1 million in the next 35 years. By then, total care costs will top $1.5 trillion.
An estimated 72 million American adults are obese -- representing about 30 percent of the nation's adult population, according to the Centers for Disease Control and Prevention. Annual health care costs for obesity in the United States range between $147 billion to $210 billion.
As a research institution devoted to promoting lifelong health, USC has more than 70 researchers across a range of disciplines who are examining the health, societal and political effects and implications of the disease. In the past decade, the National Institute on Aging has nearly doubled its investment in USC research. The investments include an Alzheimer Disease Research Center.
ApoE4 and ApoE3 are two variants of a gene that codes for a protein, apolipoprotein E, which binds fats and cholesterol to transport them to the body's lymphatic and circulatory systems and to the brain. The ApoE4 variant is linked to increased inflammation, Alzheimer's and cardiovascular disease.
ApoE3, which does not increase risk for the disease, is much more common variant, appearing in an estimated 70 to 75 percent of the population. ApoE4 appears in around 10 to 15 percent of the population.
Science has shown that Alzheimer's affects more women than men. Having one copy of ApoE4 quadruples women's risk for developing the disease. But having two copies of ApoE4 is an issue for men and women, raising their risk for the disease by a factor of 10.
Still, some people with ApoE3 and ApoE4 never develop Alzheimer's. Knowing this, Pike wanted to explore whether obesity and diet, in the presence of either gene, would affect the disease's development.
For 12 weeks, a group of mice with ApoE4 were placed on a control diet that was 10 percent fat and 7 percent sucrose, while another group of mice with ApoE4 ate a Western diet that was of 45 percent fat and 17 percent sucrose. A similar test was run on mice with ApoE3.
On the unhealthy diet, both the mice with ApoE4 and those with ApoE3 gained weight and became pre-diabetic. But most significantly, those with ApoE4 on the unhealthy diet quickly developed the signature plaques that obstruct cognition and memory.
However, Alzheimer's symptoms did not worsen for the ApoE3 mice that ate a Western diet.
"What happens to you in life is a combination of the genes that you have, the environment and behaviors, such as diet," Pike said. "Our thinking is that the risk of Alzheimer's associated with obesity is going to be regulated to some degree by the genes that we have."
The results in the mice indicate a relationship between diet and the growth of plaques and other signs of brain inflammation for mice with ApoE4.
Pike said further study is needed to understand the relationship between the two. Research already has shown that even a brief spate of poor diet can inflame glia, the brain cells responsible for immunity response.
"That means there are probably components directly in the diet, and one of those are fatty acids, like palmitic acid, that trigger inflammation because they can go in and directly affect glia," Pike said. "But that may be just one inflammation-related component of Alzheimer's disease."
"There's probably a variety of different signals that affect the brain," he added. "People even suggest that signals coming from the gut -- the microbiome -- are influential."
Pike noted that women and men with risk factors for Alzheimer's may also respond differently to the effects of diet -- an issue worth further exploration, he said.
For the study, researchers at the USC Davis School of Gerontology compared the effects of a poor diet on groups of mice that either had the Alzheimer's-associated ApoE4 gene or the relatively benign variant of the gene, ApoE3. After eating an unhealthy diet, the mice with the ApoE4 gene showed more Alzheimer's plaques -- a marker for inflammation -- in their brains, but those with ApoE3 did not.
"Part of what the results are saying is that risk doesn't affect everybody the same, and that's true for most risk factors," said Christian Pike, the lead author of the study and a professor for the USC Davis School of Gerontology. "Your genes have a big role in what happens to you, but so does your environment and your modifiable lifestyle factors. How much you exercise becomes important and what you eat becomes important."
Alzheimer's and obesity are among the intractable problems that USC researchers in multiple disciplines are seeking to unravel.
Both are widespread and costly. An estimated 5.4 million Americans have Alzheimer's, which costs an estimated $286 billion a year. The USC Schaeffer Center for Health Policy and Economics predicts the number of U.S. patients diagnosed with Alzheimer's will more than double to 9.1 million in the next 35 years. By then, total care costs will top $1.5 trillion.
An estimated 72 million American adults are obese -- representing about 30 percent of the nation's adult population, according to the Centers for Disease Control and Prevention. Annual health care costs for obesity in the United States range between $147 billion to $210 billion.
As a research institution devoted to promoting lifelong health, USC has more than 70 researchers across a range of disciplines who are examining the health, societal and political effects and implications of the disease. In the past decade, the National Institute on Aging has nearly doubled its investment in USC research. The investments include an Alzheimer Disease Research Center.
ApoE4 and ApoE3 are two variants of a gene that codes for a protein, apolipoprotein E, which binds fats and cholesterol to transport them to the body's lymphatic and circulatory systems and to the brain. The ApoE4 variant is linked to increased inflammation, Alzheimer's and cardiovascular disease.
ApoE3, which does not increase risk for the disease, is much more common variant, appearing in an estimated 70 to 75 percent of the population. ApoE4 appears in around 10 to 15 percent of the population.
Science has shown that Alzheimer's affects more women than men. Having one copy of ApoE4 quadruples women's risk for developing the disease. But having two copies of ApoE4 is an issue for men and women, raising their risk for the disease by a factor of 10.
Still, some people with ApoE3 and ApoE4 never develop Alzheimer's. Knowing this, Pike wanted to explore whether obesity and diet, in the presence of either gene, would affect the disease's development.
For 12 weeks, a group of mice with ApoE4 were placed on a control diet that was 10 percent fat and 7 percent sucrose, while another group of mice with ApoE4 ate a Western diet that was of 45 percent fat and 17 percent sucrose. A similar test was run on mice with ApoE3.
On the unhealthy diet, both the mice with ApoE4 and those with ApoE3 gained weight and became pre-diabetic. But most significantly, those with ApoE4 on the unhealthy diet quickly developed the signature plaques that obstruct cognition and memory.
However, Alzheimer's symptoms did not worsen for the ApoE3 mice that ate a Western diet.
"What happens to you in life is a combination of the genes that you have, the environment and behaviors, such as diet," Pike said. "Our thinking is that the risk of Alzheimer's associated with obesity is going to be regulated to some degree by the genes that we have."
The results in the mice indicate a relationship between diet and the growth of plaques and other signs of brain inflammation for mice with ApoE4.
Pike said further study is needed to understand the relationship between the two. Research already has shown that even a brief spate of poor diet can inflame glia, the brain cells responsible for immunity response.
"That means there are probably components directly in the diet, and one of those are fatty acids, like palmitic acid, that trigger inflammation because they can go in and directly affect glia," Pike said. "But that may be just one inflammation-related component of Alzheimer's disease."
"There's probably a variety of different signals that affect the brain," he added. "People even suggest that signals coming from the gut -- the microbiome -- are influential."
Pike noted that women and men with risk factors for Alzheimer's may also respond differently to the effects of diet -- an issue worth further exploration, he said.
A gene mutation may accelerate the loss of
memory and thinking skills in people who are at risk for Alzheimer's
disease, according to a study published in the May 3, 2017, online issue
of Neurology®, the medical journal of the American
Academy of Neurology. The gene mutation is called the BDNF Val66Met
allele, or just the Met allele.
Brain derived neurotrophic factor (BDNF) is a protein produced by the
gene of the same name. It is one of a group of proteins called
neurotrophins that help nerve cells grow, specialize and survive.
Alleles are parts of genes that work in pairs on the chromosomes to
determine a person's traits.
"We found that people with Alzheimer's risk who have this BDNF gene mutation called the Met allele may have a more rapid decline of memory and thinking skills," said study author Ozioma Okonkwo, PhD, of the University of Wisconsin School of Medicine in Madison, Wisc. "Because this gene can be detected before the symptoms of Alzheimer's start, and because this presymptomatic phase is thought to be a critical period for treatments that could delay or prevent the disease, it could be a great target for early treatments."
For the study, researchers followed 1,023 people with an average age of 55 for up to 13 years who were at risk for Alzheimer's disease but at the start were still healthy. Participants gave blood samples which were tested for the Met allele gene mutation. Their memory and thinking skills were evaluated at the start of the study and at each study visit, up to five visits. Of that group, 140 were also tested with neuroimaging for beta-amyloid, a sticky protein that can build up into plaques found in the brains of people with Alzheimer's disease.
A total of 32 percent of the participants had the Met allele. Researchers found that when compared to people without the gene mutation, those with the mutation lost memory and thinking skills more rapidly. On tests of verbal learning and memory, those with no gene mutation improved by 0.002 units per year, while the scores of people with the mutation declined by 0.021 units per year.
The researchers also found that people with the gene mutation who also had more beta-amyloid had an even steeper rate of decline.
"When there is no mutation, it is possible the BDNF gene and the protein it produces are better able to be protective, thereby preserving memory and thinking skills," Okonkwo said. "This is especially interesting because previous studies have shown that exercise can increase levels of BDNF. It is critical for future studies to further investigate the role that the BDNF gene and protein have in beta-amyloid accumulation in the brain."
A major strength of the study is that it was one of the largest studies investigating this mutation. A limitation is that the study participants were predominantly white. Also, the number of people with beta-amyloid data was limited.
"We found that people with Alzheimer's risk who have this BDNF gene mutation called the Met allele may have a more rapid decline of memory and thinking skills," said study author Ozioma Okonkwo, PhD, of the University of Wisconsin School of Medicine in Madison, Wisc. "Because this gene can be detected before the symptoms of Alzheimer's start, and because this presymptomatic phase is thought to be a critical period for treatments that could delay or prevent the disease, it could be a great target for early treatments."
For the study, researchers followed 1,023 people with an average age of 55 for up to 13 years who were at risk for Alzheimer's disease but at the start were still healthy. Participants gave blood samples which were tested for the Met allele gene mutation. Their memory and thinking skills were evaluated at the start of the study and at each study visit, up to five visits. Of that group, 140 were also tested with neuroimaging for beta-amyloid, a sticky protein that can build up into plaques found in the brains of people with Alzheimer's disease.
A total of 32 percent of the participants had the Met allele. Researchers found that when compared to people without the gene mutation, those with the mutation lost memory and thinking skills more rapidly. On tests of verbal learning and memory, those with no gene mutation improved by 0.002 units per year, while the scores of people with the mutation declined by 0.021 units per year.
The researchers also found that people with the gene mutation who also had more beta-amyloid had an even steeper rate of decline.
"When there is no mutation, it is possible the BDNF gene and the protein it produces are better able to be protective, thereby preserving memory and thinking skills," Okonkwo said. "This is especially interesting because previous studies have shown that exercise can increase levels of BDNF. It is critical for future studies to further investigate the role that the BDNF gene and protein have in beta-amyloid accumulation in the brain."
A major strength of the study is that it was one of the largest studies investigating this mutation. A limitation is that the study participants were predominantly white. Also, the number of people with beta-amyloid data was limited.
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