Tomorrow's *New York Times* (Tuesday, May 26) includes an article: "ABrain Disorder Easily Missed" by Jane Brody.Here are some excerpts:
Edward Ferguson, a civil engineer living in Vancouver, Wash., retired atage 65 from a job handling multimillion-dollar contracts.Five years later he could not balance a checkbook, walk without falling,drive a car, control his bladder or recognize his granddaughter.Instead of the active retirement he had anticipated, Mr. Ferguson, now74, thought he would spend the rest of his life in a wheelchair,incontinent and struggling with dementia.
Ten doctors were unable to tell him what was wrong, but an Internetsearch by his daughter found a condition that seemed to match hissymptoms: normal pressure hydrocephalus, or N.P.H.
The disorder involves a build-up of spinal fluid in the ventricles ofthe brain, causing pressure on nerves that control the legs, balance,bladder and cognitive function."It's as if the brain has reverted to babyhood," Dr. Michael Kaplitt, aneurosurgeon at NewYork-Presbyterian Hospital/Weill Cornell MedicalCenter, said in an interview."Like babies, people with N.P.H. walk slowly with feet wide apart, theyare incontinent and have no memory."Dr. Kaplitt calls it "a classic triad of symptoms" that should alertdoctors to the possibility of N.P.H.Yet the condition is frequently misdiagnosed as dementia, Alzheimer'sdisease, Parkinson's disease or a spinal problem.Or it is attributed to age -- nearly all who are affected are over 55.
Two days after surgery to install a programmable shunt that relieved thepressure on the frontal lobes of his brain, Mr. Ferguson walked across aroom for the first time in a year.He was able to think and write clearly, and his incontinence improved.The Fergusons are now looking forward to their 56th anniversary. Mr.Ferguson, who had contemplated suicide, considers himself to have asecond chance at life."At one point I saw no light at the end of the tunnel," he said, "andnow it is just so beautiful there."
No one knows how often N.P.H. occurs because it is so often missed ormisdiagnosed. Estimates range from 50,000 to 375,000 people in theUnited States, with the higher figure more likely to be correct, saidDr. Mark Luciano, a neurosurgeon at the Cleveland Clinic."There are a lot of people out there with a correctable problem that isattributed to old age," Dr. Luciano said."When the problem is fixed, it's like rescuing them from oblivion.A small percentage of people with dementia -- maybe 10 or 15 percent --really have N.P.H."The disorder was recognized and named in 1965.But most doctors who treat older people are unaware of it or fail tothink of it when treating patients with classic, albeit confusing, symptoms.
Normal pressure hydrocephalus is best diagnosed by a team that includesa radiologist, neuropsychologist and neurologist or neurosurgeonexperienced in distinguishing this condition.
The best clue often comes from a careful medical history, since N.P.H.typically starts with gait problems, Dr. Luciano and his colleague, Dr.Ronan Factora, a geriatrician at the Cleveland Clinic, reported lastyear in the journal Geriatrics.Cognitive impairment typically does not precede gait problems, theysaid, but when it does, or when dementia has become severe, the responseto treatment is lessened. Incontinence, which starts out as urinary urgency, can occur at any pointin the disease, and is often worsened by problems with walking or dementia.
Although there is no one route to diagnosis, if N.P.H. is suspected, aCT scan or M.R.I. of the brain can reveal one or more enlargedventricles, an essential feature of the condition.On an M.R.I., Dr. Kaplitt said, the spinal fluid often is cloudy or turbulent.Treating N.P.H. involves inserting a shunt into the brain to drain offaccumulating spinal fluid and divert it to the abdomen, where it can bereabsorbed into the bloodstream.The ideal shunt has a valve and can be reprogrammed to regulate the drainage.Repeat surgery is a possibility if the shunt drains off too much or toolittle spinal fluid.While the shunt is not a cure for N.P.H., in the 70 to 80 percent ofpatients who benefit from it, it may give them a decade or more of near-normal life, the experts said
Tuesday, May 26, 2009
Sunday, May 24, 2009
Alzheimer's Discovery Could Bring Early Diagnosis and Treatment Closer
ScienceDaily (May 23, 2009) — A discovery made by researchers at McGill University and the affiliated Lady Davis Research Institute for Medical Research at Montreal's Jewish General Hospital offers new hope for the early diagnosis and treatment of Alzheimer's disease.
In a study published in the Journal of Biological Chemistry on May 15, Dr. Hemant Paudel, his PhD student Dong Han and postdoctoral fellows Hamid Qureshi and Yifan Lu, report that the addition of a single phosphate to an amino acid in a key brain protein is a principal cause of Alzheimer's.
Identifying this phosphate, one of up to two-dozen such molecules, could make earlier diagnosis of Alzheimer's possible and might, in the longer term, lead to the development of drugs to block its onset.
The crucial protein, called a tau protein, is a normal part of the brain and central nervous system. But in Alzheimer's patients, tau proteins go out of control and form tangles that, along with senile plaques, are the primary cause of the degenerative disease.
Several years ago, it was discovered that tau proteins in normal brains contain only three to four attached phosphates, while abnormal tau in Alzheimer's patients have anywhere from 21 to 25 additional phosphates.
Paudel and his team have discovered that it is the addition of a single phosphate to the Ser202 amino acid within the tau brain protein that is the principal culprit responsible for Alzheimer's.
"The impact of this study is twofold," said Paudel, associate professor at McGill's Dept. of Neurology and Neurosurgery, and Project Director at the Bloomfield Centre for Research in Aging at the Lady Davis. "We can now do brain imaging at the earliest stages of the disease. We don't have to look for many different tau phosphates, just this single phosphate. The possibility of early diagnosis now exists.
"Second, the enzyme which puts this phosphate on the tau can be targeted by drugs, so therapies can be developed. This discovery gives us, for the first time, a clear direction towards the early diagnosis and treatment of Alzheimer's."
Paudel and his students worked for years to exclude the phosphates not directly responsible for causing Alzheimer's symptoms. They finally succeeded by working with FTDP-17, a genetic disease with symptoms similar to Alzheimer's, but transmitted via mutations. By genetically manipulating these mutations, they were able to prove that the phosphate on Ser202 almost single-handedly is responsible for the tau abnormalities that cause both FTDP-17 and Alzheimer's.
The disease leads to severe mental degeneration and almost-inevitable death, and there is no known cure, nor even a reliable technique for early diagnosis. A patient is diagnosed with advanced Alzheimer's in the United States every 70 seconds, and deaths due to the disease have increased by a staggering 47 per cent since 2000. With the Baby Boomer population aging, those numbers are expected to explode even further in coming decades.
There are more than 5.3 million people with Alzheimer's in the United States, and more than 300,000 in Canada. Every one of those patients faces years of increasing mental incapacity followed by almost certain death, with no hope of treatment. The U.S. Alzheimer's Association has called the current situation a "crisis."
In a study published in the Journal of Biological Chemistry on May 15, Dr. Hemant Paudel, his PhD student Dong Han and postdoctoral fellows Hamid Qureshi and Yifan Lu, report that the addition of a single phosphate to an amino acid in a key brain protein is a principal cause of Alzheimer's.
Identifying this phosphate, one of up to two-dozen such molecules, could make earlier diagnosis of Alzheimer's possible and might, in the longer term, lead to the development of drugs to block its onset.
The crucial protein, called a tau protein, is a normal part of the brain and central nervous system. But in Alzheimer's patients, tau proteins go out of control and form tangles that, along with senile plaques, are the primary cause of the degenerative disease.
Several years ago, it was discovered that tau proteins in normal brains contain only three to four attached phosphates, while abnormal tau in Alzheimer's patients have anywhere from 21 to 25 additional phosphates.
Paudel and his team have discovered that it is the addition of a single phosphate to the Ser202 amino acid within the tau brain protein that is the principal culprit responsible for Alzheimer's.
"The impact of this study is twofold," said Paudel, associate professor at McGill's Dept. of Neurology and Neurosurgery, and Project Director at the Bloomfield Centre for Research in Aging at the Lady Davis. "We can now do brain imaging at the earliest stages of the disease. We don't have to look for many different tau phosphates, just this single phosphate. The possibility of early diagnosis now exists.
"Second, the enzyme which puts this phosphate on the tau can be targeted by drugs, so therapies can be developed. This discovery gives us, for the first time, a clear direction towards the early diagnosis and treatment of Alzheimer's."
Paudel and his students worked for years to exclude the phosphates not directly responsible for causing Alzheimer's symptoms. They finally succeeded by working with FTDP-17, a genetic disease with symptoms similar to Alzheimer's, but transmitted via mutations. By genetically manipulating these mutations, they were able to prove that the phosphate on Ser202 almost single-handedly is responsible for the tau abnormalities that cause both FTDP-17 and Alzheimer's.
The disease leads to severe mental degeneration and almost-inevitable death, and there is no known cure, nor even a reliable technique for early diagnosis. A patient is diagnosed with advanced Alzheimer's in the United States every 70 seconds, and deaths due to the disease have increased by a staggering 47 per cent since 2000. With the Baby Boomer population aging, those numbers are expected to explode even further in coming decades.
There are more than 5.3 million people with Alzheimer's in the United States, and more than 300,000 in Canada. Every one of those patients faces years of increasing mental incapacity followed by almost certain death, with no hope of treatment. The U.S. Alzheimer's Association has called the current situation a "crisis."
Tuesday, May 12, 2009
Women More Likely To Experience Non-Traditional Stroke Symptoms
ScienceDaily (May 12, 2009) — The traditional stroke symptoms are well known and include a sudden onset of numbness or weakness on one side of the body, trouble talking, loss of vision, or coordination problems.
But in women, doctors and bystanders should be paying attention to something else, says Lynda Lisabeth, Ph.D., MPH, researcher in the department of neurology at the University of Michigan Health System.
“What we’re finding is that women experience what is considered non-traditional symptoms,” said Lisabeth, who presented research findings on acute stroke symptoms at the 2009 International Stroke Conference this spring. “The non-traditional symptom that stood out was altered mental status, meaning confusion, disorientation or a loss of consciousness.”
Symptoms such as sudden numbness of the face, arm or leg are a warning sign of what’s happening in the body during a stroke which is a loss of blood supply to the brain because of a blocked or ruptured artery.
While larger scale studies focusing on stroke in women are warranted, the gender differences U-M researchers identified may contribute to delay in treatment for women and could signal a need to change public health campaigns, Lisabeth says.
The U-M study examined ischemic strokes, the kind experienced by 80 percent of stroke victims, and transient ischemic attack, called mini-strokes because symptoms go away quickly. Researchers examined the cases of 461 men and women and classified their symptoms as either traditional or non-traditional.
Altered mental status was the most common non-traditional symptom and it was more likely to be reported in women, the study showed. Researchers do not know why women’s symptoms were different.
But the differences in symptoms may have consequences if slow recognition of stroke signs cause a delay in treatment, the researcher says.
“The only treatment that is currently FDA approved in the United States for stroke is tPA (tissue plasminogen activator), or what we call a clot-busting drug,” Lisabeth says. “To administer tPA, people with stroke have to get to the hospital within three hours of symptom onset. So any delay on the part of actually getting to the hospital or delays once at the hospital could literally mean the difference between getting the therapy, or not getting the therapy.”
Each year 800,000 Americans experience a stroke. Hispanic Americans and African Americans have a greater risk having a stroke, and to die from it. Intensive rehabilitation can help some overcome loss of function, but stroke remains a leading cause of disability. It is the third leading cause of death.
Men have an increased risk of stroke across most age groups. But in the oldest age groups, women’s risk is higher, and since women live longer than men, women actually have an increased lifetime risk for stroke.
Several studies have suggested that women experience greater in-hospital delays such as longer triage times, longer time to see a physician and longer times to head imaging, which is critical for the diagnosis of stroke, compared with men, and have 30 percent lower odds of receiving tPA. Causes of these disparities are unclear, but could result from the different symptom presentation in women.
“We’re hoping to understand those clinical implications and that information may lend itself to targeting stroke public health messages to women so that they can understand what it means to have one of these non-traditional stroke symptoms, and again emphasizing the urgency to seek care,” says Lisabeth, who is also an assistant professor in the department of epidemiology in the U-M School of Public Health.
Recognizing an ischemic stroke
Strokes are a medical emergency, and if you notice one or more of these signs, don’t wait. Call 9-1-1, or emergency medical services.
Sudden numbness or weakness of the face, arm or leg, especially on one side of the body;
Sudden confusion, trouble speaking or understanding
Sudden trouble seeing in one or both eyes
Sudden trouble walking, dizziness, loss of balance or coordination
Sudden severe headache with no known cause.
But in women, doctors and bystanders should be paying attention to something else, says Lynda Lisabeth, Ph.D., MPH, researcher in the department of neurology at the University of Michigan Health System.
“What we’re finding is that women experience what is considered non-traditional symptoms,” said Lisabeth, who presented research findings on acute stroke symptoms at the 2009 International Stroke Conference this spring. “The non-traditional symptom that stood out was altered mental status, meaning confusion, disorientation or a loss of consciousness.”
Symptoms such as sudden numbness of the face, arm or leg are a warning sign of what’s happening in the body during a stroke which is a loss of blood supply to the brain because of a blocked or ruptured artery.
While larger scale studies focusing on stroke in women are warranted, the gender differences U-M researchers identified may contribute to delay in treatment for women and could signal a need to change public health campaigns, Lisabeth says.
The U-M study examined ischemic strokes, the kind experienced by 80 percent of stroke victims, and transient ischemic attack, called mini-strokes because symptoms go away quickly. Researchers examined the cases of 461 men and women and classified their symptoms as either traditional or non-traditional.
Altered mental status was the most common non-traditional symptom and it was more likely to be reported in women, the study showed. Researchers do not know why women’s symptoms were different.
But the differences in symptoms may have consequences if slow recognition of stroke signs cause a delay in treatment, the researcher says.
“The only treatment that is currently FDA approved in the United States for stroke is tPA (tissue plasminogen activator), or what we call a clot-busting drug,” Lisabeth says. “To administer tPA, people with stroke have to get to the hospital within three hours of symptom onset. So any delay on the part of actually getting to the hospital or delays once at the hospital could literally mean the difference between getting the therapy, or not getting the therapy.”
Each year 800,000 Americans experience a stroke. Hispanic Americans and African Americans have a greater risk having a stroke, and to die from it. Intensive rehabilitation can help some overcome loss of function, but stroke remains a leading cause of disability. It is the third leading cause of death.
Men have an increased risk of stroke across most age groups. But in the oldest age groups, women’s risk is higher, and since women live longer than men, women actually have an increased lifetime risk for stroke.
Several studies have suggested that women experience greater in-hospital delays such as longer triage times, longer time to see a physician and longer times to head imaging, which is critical for the diagnosis of stroke, compared with men, and have 30 percent lower odds of receiving tPA. Causes of these disparities are unclear, but could result from the different symptom presentation in women.
“We’re hoping to understand those clinical implications and that information may lend itself to targeting stroke public health messages to women so that they can understand what it means to have one of these non-traditional stroke symptoms, and again emphasizing the urgency to seek care,” says Lisabeth, who is also an assistant professor in the department of epidemiology in the U-M School of Public Health.
Recognizing an ischemic stroke
Strokes are a medical emergency, and if you notice one or more of these signs, don’t wait. Call 9-1-1, or emergency medical services.
Sudden numbness or weakness of the face, arm or leg, especially on one side of the body;
Sudden confusion, trouble speaking or understanding
Sudden trouble seeing in one or both eyes
Sudden trouble walking, dizziness, loss of balance or coordination
Sudden severe headache with no known cause.
Monday, May 11, 2009
Memory For Different Smells: Synaptic Memory Found In Olfactory Bulb
ScienceDaily (May 9, 2009) — Ben W. Strowbridge, Ph.D, associate professor of Neuroscience and Physiology/Biophysics, and Yuan Gao, a Ph.D. student in the neurosciences program at Case Western Reserve University School of Medicine, are the first to discover a form of synaptic memory in the olfactory bulb, the part of the brain that processes the sense of smell.
In the 1970s, scientists discovered that elemental connections between brain cells, called synapses, could change their strength following brief periods of activity. This process, called long-term potentiation (LTP), is the leading candidate to explain how we store information about specific places, names and events. While laboratories around the world have found LTP in nearly every part of the mammalian brain there was one glaring exception: the part of the brain that first processes the sense of smell, the olfactory bulb.
Gao, a fourth-year graduate student, had learned that damaging olfactory sensory pathways prevents sheep from forming selective bonds with her own lambs, causing them to adopt lambs from other mothers. This cued her curiosity as to how a mother ewe forms such a selective bond with her lamb within several hours of parturition, a bond that is primarily dependent on olfactory sensory recognition.
Using an innovative home-built laser microscope, Strowbridge and Gao were able to determine that the olfactory bulb does in fact have LTP. This specialized microscope used an advanced imaging technique called "2-photon excitation" which enabled the researchers to see entire brain cells and then test whether different types of inputs to the cell could mediate olfactory memory.
"The real surprise in the study was the specific brain connection that changed following experience. It was a rarely-studied brain projection from the cortex back to the olfactory bulb" said Strowbridge.
Neuroscientists commonly believe that the way the brain processes information is similar to climbing a pyramid—starting from the bottom and working up to the top. All of the sensory systems have a large number of low-level cells that do very simple things (forming the base of the pyramid), and then they feed their results to brain areas higher up the pyramid. The brain cells in these "higher" regions begin to reflect abstract concepts, such as the shape of human faces, in the visual system or melodies in the auditory system. The brain areas related to our conscious perception of the world are presumably at the top of pyramid.
However, the Case Western Reserve University researchers found that the brain circuit had the ability to change with experience was unexpectedly a connection from high in the pyramid (the olfactory cortex) back to a lower level (the olfactory bulb).
One of the implications of Strowbridge and Gao's work is that the brain may learn about different smells by having higher brain areas first make a prediction about which scent it might be, and then test that prediction against the actual sensory data coming into the brain.
"Our work suggests that there is much more talking back-and-forth between higher and lower brain areas during olfactory learning," continued Strowbridge. "We are just beginning to explore the function of the feedback circuits that inform low-level parts of the brain, like the olfactory bulb, about predictions made by higher-order brain regions. The 2-photon microscope used in this study is an ideal tool to ask what these different brain circuits are actually doing."
Previous studies had suggested that the circuit changes associated with olfactory learning, such as sheep learning to recognize their own lambs though their characteristic scents, involved changes in the olfactory bulb. Strowbridge and Gao discovered that certain olfactory brain circuits can change with experience. This discovery provides a possible explanation for how animals can form memories of particular scents.
In 2006, Strowbridge's grouped discovered a new type of brain cell, the Blanes cell, in the olfactory bulb, also using the same home-built 2-photon microscope. Ramón y Cajal, an important Spanish anatomist, had drawn pictures of these cells and named them for one of his medical students in the late 1800s. They stayed a curiosity item in very old textbooks until Strowbridge's laboratory found that they represented a very important cell type in the brain. Using 2-photon imaging, the CWRU group showed that Blanes cells have unusual properties that may help the brain maintain memories of smells and also opened a new approach to understanding the basis of memory impairment in Alzheimer's disease. That study was published in the March 16, 2006 issue of the journal Neuron.
This study was funded by the National Institutes of Health. The 2-photon laser microscope used in the study was constructed with support from the Mount Sinai Health Care Foundation.
In the 1970s, scientists discovered that elemental connections between brain cells, called synapses, could change their strength following brief periods of activity. This process, called long-term potentiation (LTP), is the leading candidate to explain how we store information about specific places, names and events. While laboratories around the world have found LTP in nearly every part of the mammalian brain there was one glaring exception: the part of the brain that first processes the sense of smell, the olfactory bulb.
Gao, a fourth-year graduate student, had learned that damaging olfactory sensory pathways prevents sheep from forming selective bonds with her own lambs, causing them to adopt lambs from other mothers. This cued her curiosity as to how a mother ewe forms such a selective bond with her lamb within several hours of parturition, a bond that is primarily dependent on olfactory sensory recognition.
Using an innovative home-built laser microscope, Strowbridge and Gao were able to determine that the olfactory bulb does in fact have LTP. This specialized microscope used an advanced imaging technique called "2-photon excitation" which enabled the researchers to see entire brain cells and then test whether different types of inputs to the cell could mediate olfactory memory.
"The real surprise in the study was the specific brain connection that changed following experience. It was a rarely-studied brain projection from the cortex back to the olfactory bulb" said Strowbridge.
Neuroscientists commonly believe that the way the brain processes information is similar to climbing a pyramid—starting from the bottom and working up to the top. All of the sensory systems have a large number of low-level cells that do very simple things (forming the base of the pyramid), and then they feed their results to brain areas higher up the pyramid. The brain cells in these "higher" regions begin to reflect abstract concepts, such as the shape of human faces, in the visual system or melodies in the auditory system. The brain areas related to our conscious perception of the world are presumably at the top of pyramid.
However, the Case Western Reserve University researchers found that the brain circuit had the ability to change with experience was unexpectedly a connection from high in the pyramid (the olfactory cortex) back to a lower level (the olfactory bulb).
One of the implications of Strowbridge and Gao's work is that the brain may learn about different smells by having higher brain areas first make a prediction about which scent it might be, and then test that prediction against the actual sensory data coming into the brain.
"Our work suggests that there is much more talking back-and-forth between higher and lower brain areas during olfactory learning," continued Strowbridge. "We are just beginning to explore the function of the feedback circuits that inform low-level parts of the brain, like the olfactory bulb, about predictions made by higher-order brain regions. The 2-photon microscope used in this study is an ideal tool to ask what these different brain circuits are actually doing."
Previous studies had suggested that the circuit changes associated with olfactory learning, such as sheep learning to recognize their own lambs though their characteristic scents, involved changes in the olfactory bulb. Strowbridge and Gao discovered that certain olfactory brain circuits can change with experience. This discovery provides a possible explanation for how animals can form memories of particular scents.
In 2006, Strowbridge's grouped discovered a new type of brain cell, the Blanes cell, in the olfactory bulb, also using the same home-built 2-photon microscope. Ramón y Cajal, an important Spanish anatomist, had drawn pictures of these cells and named them for one of his medical students in the late 1800s. They stayed a curiosity item in very old textbooks until Strowbridge's laboratory found that they represented a very important cell type in the brain. Using 2-photon imaging, the CWRU group showed that Blanes cells have unusual properties that may help the brain maintain memories of smells and also opened a new approach to understanding the basis of memory impairment in Alzheimer's disease. That study was published in the March 16, 2006 issue of the journal Neuron.
This study was funded by the National Institutes of Health. The 2-photon laser microscope used in the study was constructed with support from the Mount Sinai Health Care Foundation.
New Evidence Ties Gene To Alzheimer's
ScienceDaily (May 8, 2009) — Of dozens of candidates potentially involved in increasing a person's risk for the most common type of Alzheimer's disease that affects more than 5 million Americans over the age of 65, one gene that keeps grabbing Johns Hopkins researchers' attention makes a protein called neuroglobin.
Adding to a growing body of evidence about the importance of this protein for the health of the aging brain, researchers at the McKusick-Nathans Institute of Genetic Medicine of the Johns Hopkins University School of Medicine canvassed the genetic neighborhood of neuroglobin and, for the first time in a human population, linked variation there with a risk for Alzheimer's.
Ever so slight genetic variations between individuals can and do influence the amounts of particular proteins that each specific gene ultimately produces. In this case, the team has found that individuals with genetic variations equating to less neuroglobin production have an increased risk for Alzheimer's.
"An intriguing part of this study was the high levels of neuroglobin that we found in the Alzheimer's brain, which was exactly the opposite from what we expected," says Dimitrios Avramopoulos, M.D., Ph.D., an associate professor in Hopkins' Institute of Genetic Medicine and the Department of Psychiatry.
Referring to data published in Neurobiology of Aging, Avramopoulos explains that his team measured levels of gene product in 56 different samples of human brain tissue: 30 from confirmed cases of Alzheimer's and 26 without brain disease.
The scientists found that neuroglobin levels decreased with advancing age, which, Avramopoulos points out, is consistent with risk of Alzheimer's increasing with advancing age. They also found that levels of neuroglobin were lower in women than in men, which is consistent with the fact that women have a slightly higher risk of Alzheimer's. About two times as many patients in the general population with Alzheimer's are women which, in part, can be attributed to the fact that women live longer and therefore have more of a chance to get Alzheimer's.
Having corrected for that disparity, researchers have noted a slightly higher risk in women than in men.
They were surprised to find that neuroglobin levels were higher in the brain tissue from Alzheimer's patients than that of the control group.
Counter-intuitive though it seemed at first, it actually makes sense, Avramopoulos says, especially in light of previously published studies that indicated a protective function for neuroglobin and showed that mouse brains respond to stress — in this case, a lack of oxygen — by producing more neuroglobin.
The scientists think that neuroglobin production also ramps up in reaction to the insult of the Alzheimer's disease. They hypothesize that maybe in some people it's simply not enough of a protective response to effectively defend the brain.
"The older we get, the less neuroglobin this particular gene produces in our brains — unless something stimulates the gene to produce more," Avramopoulos explains. "That something could be a stressor such as a lack of oxygen resulting from stoke or emphysema, for instance. And it looks like it also could be Alzheimer's disease.
"Further work on this gene will likely provide intervention targets for a multitude of very common conditions including Alzheimer's."
In addition to Avramopoulos, authors of the paper are Megan Szymanski, Ruihua Wang, M. Danielle Fallin and Susan S. Bassett, all of Johns Hopkins.
Journal reference:
Megan Szymanski, Ruihua Wang, M. Danielle Fallin, Susan S. Bassett, Dimitrios Avramopoulos. Neuroglobin and Alzheimer's dementia: Genetic association and gene expression changes. Neurobiology of Aging, 2008; DOI: 10.1016/j.neurobiolaging.2008.10.003
Adapted from materials provided by Johns Hopkins Medical Institutions.
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Adding to a growing body of evidence about the importance of this protein for the health of the aging brain, researchers at the McKusick-Nathans Institute of Genetic Medicine of the Johns Hopkins University School of Medicine canvassed the genetic neighborhood of neuroglobin and, for the first time in a human population, linked variation there with a risk for Alzheimer's.
Ever so slight genetic variations between individuals can and do influence the amounts of particular proteins that each specific gene ultimately produces. In this case, the team has found that individuals with genetic variations equating to less neuroglobin production have an increased risk for Alzheimer's.
"An intriguing part of this study was the high levels of neuroglobin that we found in the Alzheimer's brain, which was exactly the opposite from what we expected," says Dimitrios Avramopoulos, M.D., Ph.D., an associate professor in Hopkins' Institute of Genetic Medicine and the Department of Psychiatry.
Referring to data published in Neurobiology of Aging, Avramopoulos explains that his team measured levels of gene product in 56 different samples of human brain tissue: 30 from confirmed cases of Alzheimer's and 26 without brain disease.
The scientists found that neuroglobin levels decreased with advancing age, which, Avramopoulos points out, is consistent with risk of Alzheimer's increasing with advancing age. They also found that levels of neuroglobin were lower in women than in men, which is consistent with the fact that women have a slightly higher risk of Alzheimer's. About two times as many patients in the general population with Alzheimer's are women which, in part, can be attributed to the fact that women live longer and therefore have more of a chance to get Alzheimer's.
Having corrected for that disparity, researchers have noted a slightly higher risk in women than in men.
They were surprised to find that neuroglobin levels were higher in the brain tissue from Alzheimer's patients than that of the control group.
Counter-intuitive though it seemed at first, it actually makes sense, Avramopoulos says, especially in light of previously published studies that indicated a protective function for neuroglobin and showed that mouse brains respond to stress — in this case, a lack of oxygen — by producing more neuroglobin.
The scientists think that neuroglobin production also ramps up in reaction to the insult of the Alzheimer's disease. They hypothesize that maybe in some people it's simply not enough of a protective response to effectively defend the brain.
"The older we get, the less neuroglobin this particular gene produces in our brains — unless something stimulates the gene to produce more," Avramopoulos explains. "That something could be a stressor such as a lack of oxygen resulting from stoke or emphysema, for instance. And it looks like it also could be Alzheimer's disease.
"Further work on this gene will likely provide intervention targets for a multitude of very common conditions including Alzheimer's."
In addition to Avramopoulos, authors of the paper are Megan Szymanski, Ruihua Wang, M. Danielle Fallin and Susan S. Bassett, all of Johns Hopkins.
Journal reference:
Megan Szymanski, Ruihua Wang, M. Danielle Fallin, Susan S. Bassett, Dimitrios Avramopoulos. Neuroglobin and Alzheimer's dementia: Genetic association and gene expression changes. Neurobiology of Aging, 2008; DOI: 10.1016/j.neurobiolaging.2008.10.003
Adapted from materials provided by Johns Hopkins Medical Institutions.
Email or share this story:
addthis_pub = 'sciencedaily';
Need to cite this story in your essay, paper, or report? Use one of the following formats:
APA MLA
Johns Hopkins Medical Institutions (2009, May 8). New Evidence Ties Gene To Alzheimer's. ScienceDaily. Retrieved May 11, 2009, from http://www.sciencedaily.com /releases/2009/05/090506160540.htm
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