1. Study suggests cinnamon compounds may potentially help prevent Alzheimer’s

    May 29, 2013 by Ashley

    From the UC Santa Barbara press release via EurekAlert!:

    cinnamonCinnamon: Can the red-brown spice with the unmistakable fragrance and variety of uses offer an important benefit? The common baking spice might hold the key to delaying the onset of –– or warding off –– the effects of Alzheimer’s disease.

    That is, according to Roshni George and Donald Graves, scientists at UC Santa Barbara. The results of their study, “Interaction of Cinnamaldehyde and Epicatechin with Tau: Implications of Beneficial Effects in Modulating Alzheimer’s Disease Pathogenesis,” appears in the online early edition of the Journal of Alzheimer’s Disease, and in the upcoming Volume 36, issue 1 print edition.

    Alzheimer’s disease is the most common form of dementia, a neurodegenerative disease that progressively worsens over time as it kills brain cells. No cure has yet been found, nor has the major cause of Alzheimer’s been identified.

    However, two compounds found in cinnamon –– cinnamaldehyde and epicatechin –– are showing some promise in the effort to fight the disease. According to George and Graves, the compounds have been shown to prevent the development of the filamentous “tangles” found in the brain cells that characterize Alzheimer’s.

    Responsible for the assembly of microtubules in a cell, a protein called tau plays a large role in the structure of the neurons, as well as their function.

    “The problem with tau in Alzheimer’s is that it starts aggregating,” said George, a graduate student researcher. When the protein does not bind properly to the microtubules that form the cell’s structure, it has a tendency to clump together, she explained, forming insoluble fibers in the neuron. The older we get the more susceptible we are to these twists and tangles, Alzheimer’s patients develop them more often and in larger amounts.

    The use of cinnamaldehyde, the compound responsible for the bright, sweet smell of cinnamon, has proven effective in preventing the tau knots. By protecting tau from oxidative stress, the compound, an oil, could inhibit the protein’s aggregation. To do this, cinnamaldehyde binds to two residues of an amino acid called cysteine on the tau protein. The cysteine residues are vulnerable to modifications, a factor that contributes to the development of Alzheimer’s.

    “Take, for example, sunburn, a form of oxidative damage,” said Graves, adjunct professor in UCSB’s Department of Molecular, Cellular, and Developmental Biology. “If you wore a hat, you could protect your face and head from the oxidation. In a sense this cinnamaldehyde is like a cap.” While it can protect the tau protein by binding to its vulnerable cysteine residues, it can also come off, Graves added, which can ensure the proper functioning of the protein.

    Oxidative stress is a major factor to consider in the health of cells in general. Through normal cellular processes, free radical-generating substances like peroxides are formed, but antioxidants in the cell work to neutralize them and prevent oxidation. Under some conditions however, the scales are tipped, with increased production of peroxides and free radicals, and decreased amounts of antioxidants, leading to oxidative stress.

    Epicatechin, which is also present in other foods, such as blueberries, chocolate, and red wine, has proven to be a powerful antioxidant. Not only does it quench the burn of oxidation, it is actually activated by oxidation so the compound can interact with the cysteines on the tau protein in a way similar to the protective action of cinnamaldehyde.

    Cell membranes that are oxidized also produce reactive derivatives, such as Acrolein, that can damage the cysteines,” said George. “Epicatechin also sequesters those byproducts.”

    Studies indicate that there is a high correlation between Type 2 diabetes and the incidence of Alzheimer’s disease. The elevated glucose levels typical of diabetes lead to the overproduction of reactive oxygen species, resulting in oxidative stress, which is a common factor in both diabetes and Alzheimer’s disease. Other research has shown cinnamon’s beneficial effects in managing blood glucose and other problems associated with diabetes.

    Since tau is vulnerable to oxidative stress, this study then asks whether Alzheimer’s disease could benefit from cinnamon, especially looking at the potential of small compounds,” said George.

    Although this research shows promise, Graves said, they are “still a long way from knowing whether this will work in human beings.” The researchers caution against ingesting more than the typical amounts of cinnamon already used in cooking.

    If cinnamon and its compounds do live up to their promise, it could be a significant step in the ongoing battle against Alzheimer’s. A major risk factor for the disease –– age –– is uncontrollable. In the United States, Alzheimer’s presents a particular problem as the population lives longer and the Baby Boom generation turns gray, leading to a steep rise in the prevalance of the disease. It is a phenomenon that threatens to overwhelm the U.S. health care system. According to the Alzheimer’s Association, in 2013, Alzheimer’s disease will cost the nation $203 billion.

    Wouldn’t it be interesting if a small molecule from a spice could help?” commented Graves, “perhaps prevent it, or slow down the progression.”

     


  2. Study suggests no link between anesthesia and dementia in elderly

    May 16, 2013 by Ashley

    From the Mayo Clinic press release via HealthCanal:

    hospital stayElderly patients who receive anesthesia are no more likely to develop long-term dementia or Alzheimer’s disease than other seniors, according to new Mayo Clinic research.

    The study analyzed thousands of patients using the Rochester Epidemiology Project — which allows researchers access to medical records of nearly all residents of Olmsted County, Minn. — and found that receiving general anesthesia for procedures after age 45 is not a risk factor for developing dementia. The findings were published Wednesday, May 1, online in Mayo Clinic Proceedings.

    Researchers know that some elderly patients have problems with cognitive function for weeks, sometimes months, following surgical procedures, says senior author David Warner, M.D., a pediatric anesthesiologist at the Mayo Clinic Children’s Center.

    There has been concern that exposure to anesthesia may be associated with long-term cognitive changes including dementia, he says. The concern stems in part from a series of studies in which animals were exposed to anesthesia and lesions similar to those observed in Alzheimer’s disease appeared in the brain — including accumulation of amyloid, a protein associated with Alzheimer’s disease.

    “It’s reassuring we’re adding to the body of knowledge that there is not an association of anesthesia and surgery with Alzheimer’s,” Dr. Warner says. “There are a lot of things to worry about when an elderly person has surgery, but it seems that developing Alzheimer’s isn’t one of them.

    Researchers studied about 900 patients older than 45 who had dementia and lived in Olmsted County from 1985 to 1994. They compared that group to people of similar ages in Olmsted County who did not develop dementia during that time. Researchers found that about 70 percent of the patients in both groups needed surgery requiring general anesthesia — meaning those who had dementia and underwent surgery that included general anesthesia did not get worse, and those who did not have dementia and had surgery did not develop dementia as a result.

    Mayo Clinic anesthesiologist Juraj Sprung, M.D., Ph.D., is the study’s first author. The study was funded by Mayo Clinic and the National Center for Advancing Translational Sciences.

     


  3. Study sheds new light on early stage Alzheimer’s

    April 29, 2013 by Ashley

    From the Karolinska Institutet press release via ScienceDaily:

    The brainThe disrupted metabolism of sugar, fat and calcium is part of the process that causes the death of neurons in Alzheimer’s disease.

    Researchers from Karolinska Institutet in Sweden have now shown, for the first time, how important parts of the nerve cell that are involved in the cell’s energy metabolism operate in the early stages of the disease. These somewhat surprising results shed new light on how neuronal metabolism relates to the development of the disease.

    In the Alzheimer’s disease brain, plaques consisting of so called amyloid-beta-peptide (A?) are accumulated. It is also a well-known fact that the nerve cells of patients with Alzheimer’s disease have problems metabolising for example glucose and calcium, and that these disorders are associated with cell death. The metabolism of these substances is the job of the cell mitochondria, which serve as the cell’s power plant and supply the cell with energy.

    However, for the mitochondria to do this, they need good contact with another part of the cell called the endoplasmic reticulum (ER). The specialised region of ER that is in contact with mitochondria is called the MAM region. Earlier studies on yeast and other types of cells have shown that the deactivation of certain proteins in the MAM region disrupt the contact points between the mitochondria and the ER, preventing the delivery of energy to the cell and causing cell death.

    Now for the first time, researchers at Karolinska Institutet have studied the MAM region in nerve cells, and examined the interaction between the mitochondria and the ER in early stage Alzheimer’s disease. Although at this point in the development of the disease A? has not formed large, lumpy plaques, symptoms still appear, implying that A? that has not yet formed plaque is toxic to neurons.

    The team’s results are slightly surprising. When nerve cells are exposed to low doses of A?, it leads to an increase in the number of contact points between the mitochondria and the ER, causing more calcium to be transferred from the ER to the mitochondria. The resulting over-accumulation of calcium is toxic to the mitochondria and affects their ability to supply energy to the nerve cell.

    It’s urgent that we find out what causes neuronal death if we’re to develop molecules that check the disease,” says Maria Ankarcrona, docent and researcher at the Department of Neurobiology, Care Sciences and Society, and the Alzheimer’s Disease Research Centre of Karolinska Institutet. “In the long run we might be able to produce a drug that can arrest the progress of the disease at a stage when the patient is still able to manage their daily lives. If we can extend that period by a number of years, we’d have made great gains. Today there are no drugs that affect the actual disease process.”

    The researchers conducted their studies on mice bred to develop symptoms of Alzheimer’s disease. They also studied nerve cells from deceased Alzheimer’s patients and neurons cultivated in the laboratory.

    The study was financed by grants from the Swedish Research Council, the Swedish Alzheimer Foundation, the Gamla Tjänarinnor foundation, the Stohne Foundation and the Lundbeck Foundation, and through a donation from the Peter Thelin Family.


  4. Researchers develop new hypothesis for how Alzheimer’s could occur

    April 16, 2013 by Ashley

    From the Ruhr-University Bochum press release via EurekAlert!:

    brain puzzleA new hypothesis has been developed by researchers in Bochum on how Alzheimer’s disease could occur. They analysed the interaction of the proteins FE65 and BLM that regulate cell division. In the cell culture model, they discovered spherical structures in the nucleus that contained FE65 and BLM.

    The interaction of the proteins triggered a wrong signal for cell division. This may explain the degeneration and death of nerve cells in Alzheimer’s patients.

    The team led by Dr. Thorsten Müller and Prof. Dr. Katrin Marcus from the Department of Functional Proteomics in cooperation with the RUB’s Medical Proteome Centre headed by Prof. Helmut E. Meyer reported on the results in the “Journal of Cell Science“.

    Components of spherical structures in the nucleus identified

    The so-called amyloid precursor protein APP is central to Alzheimer’s disease. It spans the cell membrane, and its cleavage products are linked to protein deposits that form in Alzheimer patients outside the nerve cells. APP anchors the protein FE65 to the membrane, which was the focus of the current study. FE65 can migrate into the nucleus, where it plays a role in DNA replication and repair.

    Based on cells grown in the laboratory, the team led by Dr. Müller established that FE65 can unite with other proteins in the cell nucleus to form spherical structures, so-called “nuclear spheres”. Video microscopy showed that these ring-like structures merge with each other and can thus grow. “By using a special cell culture model, we were able to identify additional components of these spheres”, says Andreas Schrötter, PhD student in the working group Morbus Alzheimer at the Institute for Functional Proteomics. Among other things, the scientists found the protein BLM, which is known from Bloom’s syndrome – an extremely rare hereditary disease, which is associated with dwarfism, immunodeficiency, and an increased risk of cancer. BLM is involved in DNA replication and repair in the nucleus.

    The amount of FE65 determines the amount of BLM in the cell nucleus

    Müller’s team took a closer look at the function of FE65. By means of genetic manipulation, the researchers generated cell cultures, in which the FE65-production was reduced. A smaller amount of FE65 thus generated a smaller amount of the protein BLM in the nucleus. Instead, BLM collected in another area of the cell, the endoplasmic reticulum.

    In addition, the researchers found a lower rate of DNA replication in the genetically modified cells. In this way, FE65 influences the replication of the genetic material via the BLM protein. When the researchers cranked up the FE65-production again, the amount of BLM in the nucleus also increased again.

    FE65 as a possible trigger for Alzheimer’s

    In patients with Alzheimer’s disease, the protein APP, an interaction partner of FE65, changes. The interaction of the two molecules is important for the transport of FE65 into the nucleus, where it regulates cell division in combination with BLM. Müller’s team assumes that the altered APP-FE65 interaction mistakenly sends the cells the signal to divide. Since nerve cells normally cannot divide, they degenerate instead and die. “This hypothesis, which we pursue in the working group Morbus Alzheimer, also delivers new starting points for potential therapies, which are urgently needed for Alzheimer’s disease,” says Dr. Mueller. In the future, the team will also investigate whether and how the amount of BLM is altered in Alzheimer’s patients compared to healthy subjects.

     

     


  5. Study suggests tests to predict heart problems may be useful predictor of memory loss

    April 5, 2013 by Ashley

    From the American Academy of Neurology press release via EurekAlert!:

    doctor with patientRisk prediction tools that estimate future risk of heart disease and stroke may be more useful predictors of future decline in cognitive abilities, or memory and thinking, than a dementia risk score, according to a new study published in the April 2, 2013, print issue of Neurology®, the medical journal of the American Academy of Neurology.

    “This is the first study that compares these risk scores with a dementia risk score to study decline in cognitive abilities 10 years later,” said Sara Kaffashian, PhD, with the French National Institute of Health and Medical Research (INSERM) in Paris, France.

    The study involved 7,830 men and women with an average age of 55. Risk of heart disease and stroke (cardiovascular disease) and risk of dementia were calculated for each participant at the beginning of the study.

    The heart disease risk score included the following risk factors: age, blood pressure, treatment for high blood pressure, high density lipoprotein (HDL) cholesterol, total cholesterol, smoking, and diabetes. The stroke risk score included age, blood pressure, treatment for high blood pressure, diabetes, smoking, history of heart disease, and presence of cardiac arrhythmia (irregular heart beat).

    The dementia risk score included age, education, blood pressure, body mass index (BMI), total cholesterol, exercise, and whether a person had the APOE ?4 gene, a gene associated with dementia.

    Memory and thinking abilities were measured three times over 10 years.

    The study found that all three risk scores predicted 10-year decline in multiple cognitive tests. However, heart disease risk scores showed stronger links with cognitive decline than a dementia risk score. Both heart and stroke risk were associated with decline in all cognitive tests except memory; dementia risk was not linked with decline in memory and verbal fluency.

    Although the dementia and cardiovascular risk scores all predict cognitive decline starting in late middle age, cardiovascular risk scores may have an advantage over the dementia risk score for use in prevention and for targeting changeable risk factors since they are already used by many physicians. The findings also emphasize the importance of risk factors for cardiovascular disease such as high cholesterol and high blood pressure in not only increasing risk of heart disease and stroke but also having a negative impact on cognitive abilities,” said Kaffashian.


  6. Study links acting out of dreams to development of dementia

    April 1, 2013 by Ashley

    From the Mayo Clinic press release via ScienceDaily:

    senior home aloneThe strongest predictor of whether a man is developing dementia with Lewy bodies — the second most common form of dementia in the elderly — is whether he acts out his dreams while sleeping, Mayo Clinic researchers have discovered. Patients are five times more likely to have dementia with Lewy bodies if they experience a condition known as rapid eye movement (REM) sleep behavior disorder than if they have one of the risk factors now used to make a diagnosis, such as fluctuating cognition or hallucinations, the study found.

    The findings were being presented at the annual meeting of the American Academy of Neurology in San Diego. REM sleep behavior disorder is caused by loss of the normal muscle paralysis that occurs during REM sleep. It can appear three decades or more before a diagnosis of dementia with Lewy bodies is made in males, the researchers say. The link between dementia with Lewy bodies and the sleep disorder is not as strong in women, they add.

    “While it is, of course, true that not everyone who has this sleep disorder develops dementia with Lewy bodies, as many as 75 to 80 percent of men with dementia with Lewy bodies in our Mayo database did experience REM sleep behavior disorder. So it is a very powerful marker for the disease,” says lead investigator Melissa Murray, Ph.D., a neuroscientist at Mayo Clinic in Florida.

    The study’s findings could improve diagnosis of this dementia, which can lead to beneficial treatment, Dr. Murray says.

    Screening for the sleep disorder in a patient with dementia could help clinicians diagnose either dementia with Lewy bodies or Alzheimer’s disease,” she says. “It can sometimes be very difficult to tell the difference between these two dementias, especially in the early stages, but we have found that only 2 to 3 percent of patients with Alzheimer’s disease have a history of this sleep disorder.”

    Once the diagnosis of dementia with Lewy bodies is made, patients can use drugs that can treat cognitive issues, Dr. Murray says. No cure is currently available.

    Researchers at Mayo Clinic in Minnesota and Florida, led by Dr. Murray, examined magnetic resonance imaging, or MRI, scans of the brains of 75 patients diagnosed with probable dementia with Lewy bodies. A low-to-high likelihood of dementia was made upon an autopsy examination of the brain.

    The researchers checked the patients’ histories to see if the sleep disorder had been diagnosed while under Mayo care. Using this data and the brain scans, they matched a definitive diagnosis of the sleep disorder with a definite diagnosis of dementia with Lewy bodies five times more often than they could match risk factors, such as loss of brain volume, now used to aid in the diagnosis. The researchers also showed that low-probability dementia with Lewy bodies patients who did not have the sleep disorder had findings characteristic of Alzheimer’s disease.

    “When there is greater certainty in the diagnosis, we can treat patients accordingly. Dementia with Lewy bodies patients who lack Alzheimer’s-like atrophy on an MRI scan are more likely to respond to therapy — certain classes of drugs — than those who have some Alzheimer’s pathology,” Dr. Murray says.

    The study’s other key researchers at Mayo include neuroradiologist Kejal Kantarci, M.D., neuropsychologist Tanis J. Ferman, Ph.D., neurologist Bradley F. Boeve, M.D., and neuropathologist Dennis W. Dickson, M.D.

    The study was supported by the National Institutes of Health/National Institute on Aging [P50-AG016574, R01-AG040042, R01-AG011378, U01-AG006786], the Harry T. Mangurian, Jr., Foundation, and the Robert H. and Clarice Smith and Abigail Van Buren Alzheimer’s Disease Research Program of the Mayo Foundation.


  7. Study suggests surgical menopause may prime brain for stroke, Alzheimer’s

    March 28, 2013 by Ashley

    From the Medical College of Georgia at Georgia Regents University press release via EurekAlert!:

    surgery_prepWomen who abruptly and prematurely lose estrogen from surgical menopause have a two-fold increase in cognitive decline and dementia.

    “This is what the clinical studies indicate and our animal studies looking at the underlying mechanisms back this up,” said Brann, corresponding author of the study in the journal Brain. “We wanted to find out why that is occurring. We suspect it’s due to the premature loss of estrogen.”

    In an effort to mimic what occurs in women, Brann and his colleagues looked at rats 10 weeks after removal of their estrogen-producing ovaries that were either immediately started on low-dose estrogen therapy, started therapy 10 weeks later or never given estrogen.

    When the researchers caused a stroke-like event in the brain’s hippocampus, a center of learning and memory, they found the rodents treated late or not at all experienced more brain damage, specifically to a region of the hippocampus called CA3 that is normally stroke-resistant.

    To make matters worse, untreated or late-treated rats also began an abnormal, robust production of Alzheimer’s disease-related proteins in the CA3 region, even becoming hypersensitive to one of the most toxic of the beta amyloid proteins that are a hallmark of Alzheimer’s.

    Both problems appear associated with the increased production of free radicals in the brain. In fact, when the researchers blocked the excessive production, heightened stroke sensitivity and brain cell death in the CA3 region were reduced.

    Interestingly the brain’s increased sensitivity to stressors such as inadequate oxygen was gender specific, Brann said. Removing testes in male rats, didn’t affect stroke size or damage.

    Although exactly how it works is unknown, estrogen appears to help protect younger females from problems such as stroke and heart attack. Their risks of the maladies increase after menopause to about the same as males. Follow up studies are needed to see if estrogen therapy also reduces sensitivity to the beta amyloid protein in the CA3 region, as they expect, Brann noted.

    Brann earlier showed that prolonged estrogen deprivation in aging rats dramatically reduces the number of brain receptors for the hormone as well as its ability to prevent strokes. Damage was forestalled if estrogen replacement was started shortly after hormone levels drop, according to the 2011 study in the journal Proceedings of the National Academy of Sciences.

    The surprising results of the much-publicized Women’s Health Initiative – a 12-year study of 161,808 women ages 50-79 – found hormone therapy generally increased rather than decreased stroke risk as well as other health problems. Critics said one problem with the study was that many of the women, like Brann’s aged rats, had gone years without hormone replacement, bolstering the case that timing is everything.


  8. Study suggests why stimulating environment helps protect against Alzheimer’s

    March 21, 2013 by Ashley

    From the Brigham and Women’s Hospital press release via ScienceDaily:

    checkers“Use it or lose it.” The saying could apply especially to the brain when it comes to protecting against Alzheimer’s disease. Previous studies have shown that keeping the mind active, exercising and social interactions may help delay the onset of dementia in Alzheimer’s disease.

    Now, a new study led by Dennis Selkoe, MD, co-director of the Center for Neurologic Diseases in the BWH Department of Neurology, provides specific pre-clinical scientific evidence supporting the concept that prolonged and intensive stimulation by an enriched environment, especially regular exposure to new activities, may have beneficial effects in delaying one of the key negative factors in Alzheimer’s disease.

    The study was published online on March 6, 2013 in Neuron.

    Alzheimer’s disease occurs when a protein called amyloid beta accumulates and forms “senile plaques” in the brain. This protein accumulation can block nerve cells in the brain from properly communicating with one another. This may gradually lead to an erosion of a person’s mental processes, such as memory, attention, and the ability to learn, understand and process information.

    The BWH researchers used a wild-type mouse model when evaluating how the environment might affect Alzheimer’s disease. Unlike other pre-clinical models used in Alzheimer’s disease research, wild-type mice tend to more closely mimic the scenario of average humans developing the disease under normal environmental conditions, rather than being strongly genetically pre-disposed to the disease.

    Selkoe and his team found that prolonged exposure to an enriched environment activated certain adrenalin-related brain receptors which triggered a signaling pathway that prevented amyloid beta protein from weakening the communication between nerve cells in the brain’s “memory center,” the hippocampus. The hippocampus plays an important role in both short- and long-term memory.

    The ability of an enriched, novel environment to prevent amyloid beta protein from affecting the signaling strength and communication between nerve cells was seen in both young and middle-aged wild-type mice.

    “This part of our work suggests that prolonged exposure to a richer, more novel environment beginning even in middle age might help protect the hippocampus from the bad effects of amyloid beta, which builds up to toxic levels in one hundred percent of Alzheimer patients,” said Selkoe.

    Moreover, the scientists found that exposing the brain to novel activities in particular provided greater protection against Alzheimer’s disease than did just aerobic exercise. According to the researchers, this observation may be due to stimulation that occurred not only physically, but also mentally, when the mice moved quickly from one novel object to another.

    This work helps provide a molecular mechanism for why a richer environment can help lessen the memory-eroding effects of the build-up of amyloid beta protein with age,” said Selkoe. “They point to basic scientific reasons for the apparent lessening of AD risk in people with cognitively richer and more complex experiences during life.”


  9. Study suggests age-related dementia may begin with neurons’ inability to shed unwanted proteins

    March 20, 2013 by Ashley

    From the Genetics Society of America press release via Newswise:

    neuronsA team of European scientists from the University Medical Center Hamburg-Eppendorf (UKE) and the Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD) at the University of Cologne in Germany has taken an important step closer to understanding the root cause of age-related dementia.

    In research involving both worms and mice, they have found that age-related dementia is likely the result of a declining ability of neurons to dispose of unwanted aggregated proteins. As protein disposal becomes significantly less efficient with increasing age, the buildup of these unwanted proteins ultimately leads to the development and progression of dementia. This research appears in the March 2013 issue of the journal GENETICS.

    “By studying disease progression in dementia, specifically by focusing on mechanisms neurons use to dispose of unwanted proteins, we show how these are interconnected and how these mechanisms deteriorate over time,” said Markus Glatzel, M.D., a researcher involved in the work from the Institute of Neuropathology at UKE in Hamburg, Germany. “This gives us a better understanding as to why dementias affect older persons; the ultimate aim is to use these insights to devise novel therapies to restore the full capacity of protein disposal in aged neurons.”

    To make this discovery, scientists carried out their experiments in both worm and mouse models that had a genetically-determined dementia in which the disease was caused by protein accumulation in neurons. In the worm model, researchers in the lab of Thorsten Hoppe, Ph.D., from the CECAD Cluster of Excellence could inactivate distinct routes used for the disposal of the unwanted proteins. Results provided valuable insight into the mechanisms that neurons use to cope with protein accumulation. These pathways were then assessed in young and aged mice. This study provides an explanation of why dementias exponentially increase with age. Additionally, neuron protein disposal methods may offer a therapeutic target for the development of drugs to treat and/or prevent dementias.

    This is an exciting study that helps us understand what’s going wrong at a cellular level in age-related dementias,” said Mark Johnston, Ph.D., Editor-in-Chief of the journal GENETICS. “This research holds possibilities for future identification of substances that can prevent, stop, or reverse this cellular malfunction in humans.”

    CITATION: Schipanski, Angela, Sascha Lange, Alexandra Segref, Aljona Gutschmidt, David A. Lomas, Elena Miranda, Michaela Schweizer, Thorsten Hoppe, and Markus Glatzel
    A Novel Interaction between Aging and ER Overload in a Protein Conformational Dementia
    Genetics March 2013, 193: 865-876.


  10. Study suggests uncontrolled hypertension could increase risk for Alzheimer’s

    March 19, 2013 by Ashley

    From the University of Texas at Dallas press release via EurekAlert!:

    fitnessA study in the JAMA Neurology (formerly the Archives of Neurology) suggests that controlling or preventing risk factors such as hypertension earlier in life may limit or delay the brain changes associated with Alzheimer’s disease and other age-related neurological deterioration.

    Dr. Karen Rodrigue, assistant professor in the UT Dallas Center for Vital Longevity (CVL), was lead author on a study that looked at whether people with both hypertension and a common gene associated with risk of Alzheimer’s disease (the APOE-4 gene carried by about 20 percent of the population) had more buildup of the brain plaque (amyloid protein) associated with Alzheimer’s disease. Many scientists believe the amyloid plaque is the first symptom of Alzheimer’s disease and shows up a decade or more before Alzheimer’s symptoms of memory impairment and other cognitive difficulties begin.

    Until recently, amyloid plaque could only be seen at autopsy, but new brain scanning techniques allow scientists to see the amyloid plaque in living brains of healthy adults. Findings from both autopsy and amyloid brain scans show that at least 20 percent of normal older adults carry elevated levels of amyloid, a substance made up mostly of protein and deposited in organs and tissues.

    “I became interested in whether hypertension was related to increased risk of amyloid plaques in the brains of otherwise healthy people,” Rodrigue said. “Identifying the most significant risk factors for amyloid deposition in seemingly healthy adults will be critical in advancing medical efforts aimed at prevention and early detection.”

    Based on evidence that hypertension was associated with Alzheimer’s disease, Rodrigue suspected that the double-whammy of hypertension and presence of the APOE-e4 gene might lead to particularly high levels of amyloid plaque in healthy adults.

    Rodrigue’s research was part of the Dallas Lifespan Brain Study, a comprehensive study of the aging brain in a large group of adults of all ages funded by the National Institute on Aging. As part of this study, the research team recruited 147 participants (ages 30-89) to undergo cognitive testing, magnetic resonance imaging (MRI) and PET imaging, using Amyvid, a compound that when injected travels to the brain and binds with amyloid proteins, allowing the scientists to visualize the amount of amyloid plaque. Blood pressure was measured at each visit.

    Rodrigue classified participants in the study as hypertensive if they reported a current physician diagnosis of hypertension or if their blood pressure exceeded the established criteria for diagnosis. The participants were further divided between individuals who were taking anti-hypertensive medications and those who were not medicated, but showed blood pressure elevations consistent with a diagnosis of hypertension. Finally, study subjects were classified in the genetic risk group if they were in the 20 percent of adults who had one or two copies of an APOE ?4 allele, a genetic variation linked to dementia.

    The most striking result of the study was that unmedicated hypertensive adults who also carried a genetic risk factor for Alzheimer’s disease, showed much higher amyloid levels than all other groups. Adults taking hypertensive medications, even those with genetic risk, had levels of amyloid plaque equivalent to participants without hypertension or genetic risk.

    The study suggests that controlling hypertension may significantly decrease the risk of developing amyloid deposits, even in those with genetic risk, in healthy middle-aged and older adults. Rodrigue noted that long-term studies of many people were needed to be certain that it was the use of hypertensive medications that was causal of the decreased amyloid deposits. Nevertheless, this early finding provides a window into the potential benefits of controlling hypertension that goes beyond decreasing risk of strokes and other cardiovascular complications.

    Scientists cannot fully explain the neural mechanisms underlying the effect of hypertension and APOE ?4 on amyloid accumulation. But earlier research in animal models showed that chronic hypertension may enable easier penetration of the blood-brain barrier, resulting in more amyloid deposition.

    The recent study is significant because it focuses on a group of healthy and cognitively normal middle-aged and older adults, which enables the examination of risk factors and amyloid burden before the development of preclinical dementia. The team plans for long-term longitudinal follow-up with participants to determine which proportion of the subjects eventually develop the disease.

    The study’s coauthors included Dr. Denise Park, director of the Dallas Lifespan Brain Study, and Dr. Kristen Kennedy and doctoral student Jennifer Rieck, all from The University of Texas at Dallas. The team also included Dr. Michael Devous and Dr. Ramon Diaz-Arrastia, scientists from UT Southwestern Medical Center and the Uniformed Services University of the Health Sciences. In addition to the National Institute on Aging, the Alzheimer’s Association provided funds for the study. Avid Radiopharmaceutical provided doses of Amyvid that allowed the researchers to image the amyloid plaque with a PET scan.