April 13, 2018
NIH/National Institute on Alcohol Abuse and Alcoholism
Losing just one night of sleep led to an immediate increase in beta-amyloid, a protein in the brain associated with Alzheimer's disease, according to a small, new study.
Losing just one night of sleep led to an immediate increase in beta-amyloid, a protein in the brain associated with Alzheimer's disease, according to a small, new study by researchers at the National Institutes of Health. In Alzheimer's disease, beta-amyloid proteins clump together to form amyloid plaques, a hallmark of the disease.
While acute sleep deprivation is known to elevate brain beta-amyloid levels in mice, less is known about the impact of sleep deprivation on beta-amyloid accumulation in the human brain. The study is among the first to demonstrate that sleep may play an important role in human beta-amyloid clearance.
"This research provides new insight about the potentially harmful effects of a lack of sleep on the brain and has implications for better characterizing the pathology of Alzheimer's disease," said George F. Koob, Ph.D., director of the National Institute on Alcohol Abuse and Alcoholism (NIAAA), part of the National Institutes of Health, which funded the study.
Beta-amyloid is a metabolic waste product present in the fluid between brain cells. In Alzheimer's disease, beta-amyloid clumps together to form amyloid plaques, negatively impacting communication between neurons.
Led by Drs. Ehsan Shokri-Kojori and Nora D. Volkow of the NIAAA Laboratory of Neuroimaging, the study is now online in the Proceedings of the National Academy of Sciences. Dr. Volkow is also the director of the National Institute on Drug Abuse at NIH.
To understand the possible link between beta-amyloid accumulation and sleep, the researchers used positron emission tomography (PET) to scan the brains of 20 healthy subjects, ranging in age from 22 to 72, after a night of rested sleep and after sleep deprivation (being awake for about 31 hours). They found beta-amyloid increases of about 5 percent after losing a night of sleep in brain regions including the thalamus and hippocampus, regions especially vulnerable to damage in the early stages of Alzheimer's disease.
Read more: https://www.sciencedaily.com/releases/2018/04/180413155301.htm
In the brains of Alzheimer’s patients, many of the genes required to form new memories are shut down by a genetic blockade, contributing to the cognitive decline seen in those patients.
MIT researchers have now shown that they can reverse that memory loss in mice by interfering with the enzyme that forms the blockade. The enzyme, known as HDAC2, turns genes off by condensing them so tightly that they can’t be expressed.
For several years, scientists and pharmaceutical companies have been trying to develop drugs that block this enzyme, but most of these drugs also block other members of the HDAC family, which can lead to toxic side effects. The MIT team has now found a way to precisely target HDAC2, by blocking its interaction with a binding partner called Sp3.
“This is exciting because for the first time we have found a specific mechanism by which HDAC2 regulates synaptic gene expression,” says Li-Huei Tsai, director of MIT’s Picower Institute for Learning and Memory and the study’s senior author.
Blocking that mechanism could offer a new way to treat memory loss in Alzheimer’s patients. In this study, the researchers used a large protein fragment to interfere with HDAC-2, but they plan to seek smaller molecules that would be easier to deploy as drugs.
Picower Institute postdocs Hidekuni Yamakawa, Jemmie Cheng, and Jay Penney are the lead authors of the study, which appears in the Aug. 8 edition of Cell Reports.
Read more: http://news.mit.edu/2017/blocking-key-enzyme-may-reverse-memory-loss-0808
Your morning cup of joe may have effects that reach beyond getting you alert and ready for the day. Researchers at Indiana University identified 24compounds that can increase the brain’s production of an enzyme that could help protect it against diseases like Alzheimer’s and other forms of dementia. One of the strongest impacts on the enzyme came from caffeine, which was additionally shown to improve memory function in mice.
The enzyme, called NMNAT2, has a protective effect on the brain. Researchers previously found that the enzyme has two important functions - it can guard neurons from stress and work as a “chaperone” when it fights against misfolded proteins called tau which form age-related “plaques.”
The misfolded tau proteins are related to a host of neurogenerative diseases like Parkinson’s, Alzheimer’s and Huntington’s as well as Lou Gehrig’s disease or ALS.
"This work could help advance efforts to develop drugs that increase levels of this enzyme in the brain, creating a chemical 'blockade' against the debilitating effects of neurodegenerative disorders," said Professor Hui-Chen Lu, who led the study.
Researchers went through 1,280 compounds, which included current drugs, in an effort to figure out what can influence the production of the NMNAT2 enzyme. Besides caffeine, the world's most popular drug, scientists found that a discontinued anti-depressant drug rolipram also gives a strong boost to the helpful enzyme’s production. Other compounds that have a weaker effect on increasing the amount of NMNAT2 include ziprasidone, canthardin, wortmannin and retonoic acid (found in vitamin A).
The scientists are excited about identifying the compounds, hoping they will lead to an increase in our overall understanding of what happens in the brain due to the brain disorders. They also found 13 compounds that lower the protective enzyme.
"Increasing our knowledge about the pathways in the brain that appear to naturally cause the decline of this necessary protein is equally as important as identifying compounds that could play a role in future treatment of these debilitating mental disorders," said Lu.
The study was published in the journal Scientific Reports.
Cover photo: A young woman samples freshly-brewed cappuccino at Bonanza Coffee Roasters on January 24, 2011 in Berlin, Germany. (Photo by Sean Gallup/Getty Images)
Using a sauna may be more than just relaxing and refreshing. It may also reduce the risk for Alzheimer’s disease and other forms of dementia, a new study suggests.
Researchers in Finland analyzed medical records of 2,315 healthy men ages 42 to 60, tracking their health over an average of about 20 years. During that time, they diagnosed 204 cases of dementia and 123 cases of Alzheimer’s disease.
The study, in Age and Ageing, controlled for alcohol intake, smoking, blood pressure, diabetes and other health and behavioral factors. It found that compared with men who used a sauna once a week, those who used a sauna four to seven times a week had a 66 percent lower risk for dementia and a 65 percent lower risk for Alzheimer’s disease.
The senior author, Jari Antero Laukkanen, a professor of clinical medicine at the University of Eastern Finland, said that various physiological mechanisms may be involved. Sauna bathing may, for example, lead to reduced inflammation, better vascular function or lowered blood pressure.
“Overall relaxation and well-being can be another reason,” he added, though the findings were only an association. “We need more studies to clarify mechanisms and confirm our findings.”
Un estudio encontró que las personas que son activas y comen bien tienen menos efectos cerebrales vinculados con la enfermedad.
Por Steven Reinberg
Reportero de HealthDay
MIÉRCOLES, 17 de agosto de 2016 (HealthDay News) -- Una dieta saludable y el ejercicio regular podrían ser las claves para mantener el cerebro libre de los cambios que conducen a la enfermedad de Alzheimer, sugiere un pequeño estudio.
Los investigadores estudiaron a 44 pacientes de 40 a 85 años de edad que tenían problemas leves de memoria. Encontraron que los cerebros de los que seguían una dieta mediterránea y eran físicamente activos tenían menos placas y nudos, una característica del Alzheimer, que aquellos cuyas dietas eran menos saludables y eran menos activos.
"Se sabe que la enfermedad de Alzheimer es incurable, pero hasta hace poco no se había pensado que puede ser prevenible", comentó el investigador líder, el Dr. David Merrill, profesor clínico asistente de psiquiatría y ciencias de la conducta de la Facultad de Medicina David Geffen de la UCLA, en Los Ángeles.
Numerosos estudios han sugerido que un estilo de vida saludable se relaciona con un encogimiento cerebral reducido y unas tasas más bajas de atrofia en el tejido del cerebro, señaló.
Pero este es el primer estudio en mostrar la forma en que los factores del estilo de vida influyen de forma directa en los niveles de depósitos anómalos de proteína en el cerebro que hace mucho se han vinculado con la enfermedad de Alzheimer. Además, los sujetos del estudio fueron personas con pérdida sutil de la memoria que todavía no habían sido diagnosticadas con demencia, anotó Merrill.
"El hecho de que pudiéramos detectar esta influencia del estilo de vida a un nivel molecular en un paciente con síntomas tan iniciales nos sorprendió", dijo.
Los hallazgos refuerzan la importancia de vivir una vida saludable para la "prevención del desarrollo de la patología cerebral del Alzheimer, incluso antes del desarrollo de una demencia clínicamente significativa", planteó Merrill.
El informe aparece en la edición del 16 de agosto de la revista American Journal of Geriatric Psychiatry.
En el estudio, Merrill y sus colaboradores sometieron a los pacientes a TEP para determinar los niveles de depósitos de proteína en sus cerebros. Los investigadores observaron en específico los niveles de los depósitos de beta amiloidea en los espacios entre las células nerviosas, además de los nudos, que son ovillos de la proteína tau dentro de las células del cerebro. Ambos son indicadores del Alzheimer.
Los investigadores encontraron que los factores del estilo de vida, como un peso sano, la actividad física y una dieta mediterránea se vinculaban con unos niveles más bajos de placas y nudos.
Una dieta mediterránea es rica en frutas, verduras, legumbres, cereales y pescado, y baja en carne, lácteos y grasas saturadas.
Merrill dijo que el próximo paso es combinar escáneres del cerebro con estudios sobre los cambios en la dieta, el ejercicio y otros factores del estilo de vida, como el estrés y la salud mental.
Heather Snyder es directora principal de operaciones médicas y científicas de la Asociación del Alzheimer (Alzheimer's Association). "En el campo se está luchando con esta idea de que el estilo de vida puede influir en los cambios cerebrales vistos en la enfermedad de Alzheimer", comentó.
"De verdad deseamos comprender cómo las conductas pueden cambiar la biología subyacente vinculada con el Alzheimer", añadió Snyder.
Varias conductas parecen ser importantes para mantener el cerebro sano, sobre todo el ejercicio y gestionar los riesgos de enfermedad cardiaca, como la diabetes, la hipertensión y el colesterol alto, explicó.
"Hay muchas ideas distintas sobre qué podría estar sucediendo, pero todavía no sabemos cuál es la biología subyacente", dijo Snyder.
Mientras tanto, la Asociación del Alzheimer ofrece 10 formas de amar a su cerebro:
Ejercite el cuerpo.
Ejercite el cerebro yendo a una clase.
Controle la presión arterial y la diabetes.
Coma una dieta saludable.
Duerma bien. Trate el insomnio y la apnea del sueño.
Busque ayuda para la depresión y la ansiedad.
Sea socialmente activo.
Desafíe su mente con juegos, arte y pasatiempos.
Proteja su cabeza. Use un cinturón de seguridad, use un casco al andar en bicicleta, y tome medidas para prevenir las caídas.
La enfermedad de Alzheimer afecta a un estimado de 5.4 millones de personas en Estados Unidos, y resulta en más de 200 mil millones de dólares al año en costos de atención de la salud, según la Asociación del Alzheimer.
WASHINGTON — The death rate in the United States rose last year for the first time in a decade, preliminary federal data show, a rare increase that was driven in part by more people dying from drug overdoses, suicide and Alzheimer’s disease. The death rate from heart disease, long in decline, edged up slightly.
Death rates — measured as the number of deaths per 100,000 people — have been declining for years, an effect of improvements in health, disease management and medical technology.
While recent research has documented sharp rises in death rates among certain groups — in particular less educated whites, who have been hardest hit by the prescription drug epidemic — increases for the entire population are relatively rare.
Federal researchers cautioned that it was too early to tell whether the rising mortality among whites had pushed up the overall national death rate. (Preliminary data is not broken down by race, and final data will not be out until later this year.) But they said the rise was real, and while it is premature to ring an alarm now, if it continues, it could be a signal of distress in the health of the nation.
“It’s an uptick in mortality and that doesn’t usually happen, so it’s significant,” said Robert Anderson, the chief of mortality statistics at the National Center for Health Statistics, part of the Centers for Disease Control and Prevention. “But the question is, what does it mean? We really need more data to know. If we start looking at 2016 and we see another rise, we’ll be a lot more concerned.”
The death rate rose to 729.5 deaths per 100,000 people in 2015, up from 723.2 in 2014, according to the National Center for Health Statistics. It was one of the few times in the past 25 years that the rate has increased. A bad flu season pushed it up in 2005, and AIDS and the flu contributed to a sharp increase in 1993. In 1999, there was a tiny increase.
Experts said the current rise was surprising.
“We are not accustomed to seeing death rates increase on a national scale,” said Andrew Fenelon, a researcher at the C.D.C. who did not work on the paper. “We’ve seen increases in mortality for some groups, but it is quite rare to see it for the whole population.”
He added that it would drag the United States further behind its European peers: “Many countries in Europe are witnessing declines in mortality, so the gap between the U.S. and other countries is growing.”
Others said the finding seemed to fit the broader pattern of rising mortality among working-class whites, a trend that has drawn significant attention recently. Last year, a paper by Anne Case and Angus Deaton documented rising death rates among middle-age white Americans, particularly those with no more than a high school education. Other research has found rising rates among younger whites.
“This is probably heavily influenced by whites,” said Sam Harper, an epidemiologist at McGill University in Montreal. “It does sort of fit together.”
Chronic diseases like cancer and heart disease take by far the most American lives, far more, for example, than suicide or homicide, so any change in such causes can have a big effect on the final numbers. Dr. Anderson pointed out that the death rate from heart disease, which had been declining for decades — and offsetting the rises in drug deaths, for example — flattened. That gives other causes of death more of an influence, Dr. Anderson said, as they are no longer being offset by declines from heart disease.
The death rate from heart disease stood at 167.1 in 2015, up from 166.7 in 2014, though the rise was not statistically significant. It was the first time since 1993 that the rate did not decline, Dr. Anderson said.
The death rate from suicides rose to 13.1 in the third quarter of 2015, from 12.7 in the same quarter of 2014. (The last quarter of 2015 data was not yet available for suicides.)
The same was true for drug overdoses, whose data the report had for only the first two quarters of 2015. The death rate for overdoses rose to 15.2 in the second quarter of 2015, compared with 14.1 in the same quarter of 2014. The rate for so-called unintentional injuries, which include drug overdoses and car accidents, rose to 42 in the third quarter of 2015, up from 39.9 in the same quarter of 2014.
The rate for Alzheimer’s disease was also up, rising to 29.2 in 2015, compared with 25.4 in 2014, the continuation of some years of increases. Dr. Anderson said that part of the rise was more precise reporting of Alzheimer’s on death certificates, but that overalldementia-related deaths had increased over time.
Eating seafood is linked to a reduced risk of dementia-associated brain changes in people who carry the ApoE4 gene variation, which increases the risk for Alzheimer’s disease. Eating seafood was not linked to similar changes in those who carried other forms of the ApoE gene.
The study, published in JAMA, looked at 286 autopsied brains and also found that eating seafood was linked to increased mercury in the brain, but that mercury levels were not linked to brain abnormalities.
After controlling for age, sex, education and other factors, the researchers found that compared with those who ate less seafood, ApoE4 carriers who had one seafood meal or more a week had lower densities of the amyloid plaques and neurofibrillary tangles typical of Alzheimer’s disease. Over all, they had a 47 percent lower likelihood of having a post-mortem diagnosis of Alzheimer’s.
Consumption of fish oil supplements was not correlated with pathological brain changes.
The lead author, Martha Clare Morris, a professor of epidemiology at Rush University, said that mercury from fish appears to pose little risk for aging people. But, she said, there are studies that show that mercury consumption in pregnancy can cause cognitive problems in babies.
“Most studies in dementia have found that one seafood meal a week is beneficial,” she said, though “they haven’t found that the more you eat, the lower the risk.”
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