Chapter 7. Life-Span Development of the Brain and Behavior
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Patricia Neighmond Hoping to keep your mental edge as you get older? Look after your heart, a recent analysis suggests, and your brain will benefit, too. A research team led by Hannah Gardener, an epidemiologist at the University of Miami, analyzed a subset of data from the Northern Manhattan Study, a large, ongoing study of risk factors for stroke among whites, blacks and Hispanics living in the Washington Heights neighborhood of New York City. The scientists wanted to see how people in their 60s and 70s would do on repeated tests of memory and mental acuity six years later — and, specifically, what sort of subtle differences a heart-healthy lifestyle might make to the brain, beyond the prevention of strokes. Their findings appear in a recent issue of the Journal of the American Heart Association. In this particular study, the researchers started with more than a thousand people who'd had their cardiovascular health assessed using measures that the American Heart Association has dubbed Life's Simple 7. These seven factors known to benefit the heart and blood vessels include maintaining a normal body weight and good nutrition, not smoking, getting exercise regularly and keeping blood pressure, cholesterol and blood sugar levels under control. To measure thinking skills, Gardener's team used a variety of tests of memory, judgement, the ability to plan, mental quickness and other sorts of problem solving. The results were striking: Across all demographic groups, the people who had higher scores on the measures of cardiovascular health did better on the mental tests than those who scored low. © 2016 npr
Link ID: 22167 - Posted: 05.02.2016
Symptoms of depression that steadily increase over time in older age could indicate early signs of dementia, scientists have said. Other patterns of symptoms, such as chronic depression, appear not to be linked, a study found. Dutch researchers looked at different ways depression in older adults progressed over time and how this related to any risk. They concluded worsening depression may signal the condition is taking hold. The research, published in The Lancet Psychiatry, followed more than 3,000 adults aged 55 and over living in the Netherlands. All had depression but no symptoms of dementia at the start of the study. Dr M Arfan Ikram of the Erasmus University Medical Center in Rotterdam said depressive symptoms that gradually increase over time appear to be a better predictor of dementia later in life than other paths of depression. "There are a number of potential explanations, including that depression and dementia may both be symptoms of a common underlying cause, or that increasing depressive symptoms are on the starting end of a dementia continuum in older adults," he said. Only the group whose symptoms of depression increased over time were found to be at increased risk of dementia - about one in five of people (55 out of 255) in this group developed dementia. Others who had symptoms that waxed and waned or stayed the same were not at increased risk. For example, in those who experienced low but stable levels of depression, around 10% went on to develop dementia. The exact nature of depression on dementia risk remains unknown. © 2016 BBC
By n. r. kleinfield IT BEGAN WITH what she saw in the bathroom mirror. On a dull morning, Geri Taylor padded into the shiny bathroom of her Manhattan apartment. She casually checked her reflection in the mirror, doing her daily inventory. Immediately, she stiffened with fright. Huh? What? She didn’t recognize herself. She gazed saucer-eyed at her image, thinking: Oh, is this what I look like? No, that’s not me. Who’s that in my mirror? This was in late 2012. She was 69, in her early months getting familiar with retirement. For some time she had experienced the sensation of clouds coming over her, mantling thought. There had been a few hiccups at her job. She had been a nurse who climbed the rungs to health care executive. Once, she was leading a staff meeting when she had no idea what she was talking about, her mind like a stalled engine that wouldn’t turn over. “Fortunately I was the boss and I just said, ‘Enough of that; Sally, tell me what you’re up to,’” she would say of the episode. Certain mundane tasks stumped her. She told her husband, Jim Taylor, that the blind in the bedroom was broken. He showed her she was pulling the wrong cord. Kept happening. Finally, nothing else working, he scribbled on the adjacent wall which cord was which. Then there was the day she got off the subway at 14th Street and Seventh Avenue unable to figure out why she was there. So, yes, she had had inklings that something was going wrong with her mind. She held tight to these thoughts. She even hid her suspicions from Mr. Taylor, who chalked up her thinning memory to the infirmities of age. “I thought she was getting like me,” he said. “I had been forgetful for 10 years.”
Link ID: 22160 - Posted: 04.30.2016
By PAM BELLUCK Alzheimer’s disease can seem frightening, mysterious and daunting. There are still a lot of unknowns about the disease, which afflicts more than five million Americans. Here are answers to some common questions: Sometimes I forget what day it is or where I put my glasses. Is this normal aging, or am I developing Alzheimer’s? Just because you forgot an item on your grocery list doesn’t mean you are developing dementia. Most people have occasional memory lapses, which increase with age. The memory problems that characterize warning signs of Alzheimer’s are usually more frequent, and they begin to interfere with safe or competent daily functioning: forgetting to turn off the stove, leaving home without being properly dressed or forgetting important appointments. Beyond that, the disease usually involves a decline in other cognitive abilities: planning a schedule, following multistep directions, carrying out familiar logistical tasks like balancing a checkbook or cooking a meal. It can also involve mood changes, agitation, social withdrawal and feelings of confusion, and can even affect or slow a person’s gait. How is Alzheimer’s diagnosed? Diagnosing Alzheimer’s usually involves a series of assessments, including memory and cognitive tests. Clinicians will also do a thorough medical work-up to determine whether the thinking and memory problems can be explained by other diagnoses, such as another type of dementia, a physical illness or side effects from a medication. Brain scans and spinal taps may also be conducted to check for corroborating evidence like the accumulation of amyloid, the hallmark protein of Alzheimer’s, in the brain or spinal fluid. The cause is unknown for most cases. Fewer than 5 percent of cases are linked to specific, rare gene mutations. Those are usually early-onset cases that develop in middle age. © 2016 The New York Times Company
Link ID: 22159 - Posted: 04.30.2016
By Nicholas Bakalar Treating pregnant women for depression may benefit not just themselves but their babies as well. A study, in the May issue of Obstetrics & Gynecology, included 7,267 pregnant women, of whom 831 had symptoms of depression. After controlling for maternal age, race, income, body mass index and other health and behavioral characteristics, the researchers found that depressive symptoms were associated with a 27 percent increased relative risk of preterm birth (less than 37 weeks of gestation), an 82 percent increased risk of very preterm birth (less than 32 weeks of gestation), and a 28 percent increased risk of having a baby small for gestational age. They also found that among those who were treated with antidepressants for depression — about a fifth of those with the diagnosis — there was no association with increased risk for any of these problems. But they acknowledge that this group was quite small, which limits the power to draw conclusions. Still, the lead author, Dr. Kartik K. Venkatesh, a clinical fellow in obstetrics and gynecology at Harvard, said that it was important to screen mothers for depression, not only for their health but for that of their babies. “By screening early in pregnancy, you could identify those at higher risk and counsel them about the importance of treatment,” he said. “Treating these women for depression may have real benefits.” © 2016 The New York Times Company
It was December 2012 when the country learned about the massacre at Sandy Hook Elementary School, that left 20 children dead at the hands of 20-year-old shooter Adam Lanza. After the shock and the initial grief came questions about how it could have happened and why. Reports that Adam Lanza may have had some form of undiagnosed mental illness surfaced. The tragedy drove Liza Long to write a blog post on that same day, titled "I Am Adam Lanza's Mother." She wasn't Lanza's mom, but she was raising a child with a mental disorder. Her 13-year-old son had violent rages on a regular basis. He was in and out of juvenile detention. He had threatened to kill her. She detailed all this in her essay that took off online. Now, four years later, her son is speaking out too. This week on For The Record: a mother, a son and life on the edge of bipolar disorder. Eric Walton, Liza Long's son, is now a 16-year-old high school sophomore in Boise, Idaho. After a series of misdiagnoses, he's been diagnosed with bipolar disorder. But four years ago, he didn't know much about his condition. "I knew that there were times when I would have rages, didn't like them. I knew that I wanted them to stop," Walton says. Except he felt a loss of control in those moments. He describes the onset of these rages as a "blackout" of sorts. "I would start getting angry," he says. "Then it's like being trapped inside a box inside your own head. It was like a television on the wall that shows you what you're seeing. You can feel everything, but you no longer have the video game controller to control your own body." Walton's mom says when Eric would get into those states, "he would express a lot of suicidal thoughts, and hearing him just say, 'I want to die, I just want to end it.'" Then, two days before the Newtown shooting, Eric Walton had another episode. © 2016 npr
By Lisa L. Lewis On Tuesday, U.S. News and World Report released its annual public high-school rankings, with the School for the Talented and Gifted in Dallas earning the top spot for the fifth year in a row. The rankings are based on a wealth of data, including graduation rates and student performance on state proficiency tests and advanced exams, as well as other relevant factors—like the percentage of economically disadvantaged students the schools serve. But there’s one key metric that isn’t tracked despite having a proven impact on academic performance: school start times. First-period classes at the School for the Talented and Gifted start at 9:15 a.m. That’s unusually late compared to other schools but is in keeping with the best practices now recommended by public health experts. Teens require more sleep than adults and are hardwired to want to sleep in. Eight hours a night may be the goal for adults, but teens need between 8.5–9.5 hours, according to the American Academy of Pediatrics. Unfortunately, few teens meet that minimum: Studies show that two out of three high school students get less than eight hours of sleep, with high school seniors averaging less than seven hours. Sure, kids could go to bed earlier. But their bodies are set against them: Puberty makes it hard for them to fall asleep before 11 p.m. When combined with too-early start times, the result is sleep deprivation.
By Clare Wilson People who develop schizophrenia may have been born with brains with a different structure. The finding adds further support to the idea that genetics can play a key role in schizophrenia, which involves delusions and hallucinations and is often a lifelong condition once it develops. Schizophrenia has been the subject of a fierce nature-versus-nurture debate: childhood abuse is linked with a raised risk of the condition, but 108 genes have been implicated, too. Probing the biology of schizophrenia is difficult because brain tissue sampled from people with the condition is rarely available to study. Kristen Brennand of the Icahn School of Medicine at Mount Sinai in New York and her colleagues got around this by taking skin cells from 14 people with schizophrenia, and reprogramming them into stem cells and then nerve cells. They found that on average these nerve cells had lower levels of a signalling molecule called miR-9 than similar cells developed from people who do not have schizophrenia. A small string of nucleic acids, miR-9 can change the activity of certain genes and is known to play a role in how neurons develop in the fetus. In further experiments, Brennand’s team showed that miR-9 might also affect how neurons migrate from where they form, next to the fetal brain’s central cavities, out to their final resting place in the brain’s outer layers. © Copyright Reed Business Information Ltd.
By Esther Landhuis Peer inside the brain of someone with Alzheimer’s disease, and you’ll see some striking features: shriveled nerve cells and strange protein clumps. According to a leading theory, proteins called amyloid beta and tau build up in the brain and choke nerve cell communication, setting the disease in motion years before people suspect anything is wrong with their recall. Yet the Alzheimer’s brain has another curious aspect. Some of the clusters of toxic amyloid proteins are entangled with octopus-like immune cells called microglia, cells that live in the brain to clear unwanted clutter. By munching on amyloid plaques, microglia are thought to help keep the disease at bay. But these housekeeping cells have an additional role—they switch on inflammatory pathways. Inflammation is critically important when the immune system encounters infection or needs to repair tissue. If left unchecked, however, the inflammatory process churns out toxic substances that can kill surrounding cells, whose death triggers more inflammation and creates a vicious cycle. For years scientists have probed how neuroinflammation contributes to Alzheimer’s disease and other neurodegenerative ailments. Researchers face a number of immediate questions: Is neuroinflammation a driving force? Does it kick in when the disease is already underway and worsen the process? Could it be harnessed for good in the early stages? Those questions are far from settled, but research is starting to reveal a clearer picture. “It may not be the amyloid plaques themselves that directly damage neurons and the connections between them. Rather, it may be the immune reaction to the plaques that does the damage,” says Cynthia Lemere, a neuroscientist at Brigham and Women’s Hospital. Still, it is hard to say if microglia are good guys or bad, making it challenging to create therapeutics that target these cells. © 2016 Scientific American
Nicola Davis The proportion of older people suffering from dementia has fallen by a fifth over the past two decades with the most likely explanation being because men are smoking less and living healthier lives, according to new scientific research. A team from three British universities concluded that as a result the number of new cases of dementia is lower than had been predicted in the 1990s, estimated at around 210,000 a year in the UK as opposed to 250,000. The findings are potentially significant because they suggest that it is possible to take preventative action, such as stopping smoking and reducing cholesterol, that could help avoid the condition. “Physical health and brain health are clearly highly linked,” said Carol Brayne of Cambridge University, who co-authored the study. Nick Fox, professor of neurology at University College, London, who was not involved in the study, agrees: “This does suggest that our risk, in any particular age in later life, can be reduced probably by what we do 10, 20 or 30 years before.” The scientists found that new cases of dementia had dropped from 20.1 in every 1,000 people per year in the first study conducted in the early 1990s to 17.7 in the second, which looked at new cases between 2008 and 2013. When sex and age differences were taken into account, the dementia rates were found to have dropped by 20%. The trend emerges from a dramatic drop in new cases for men across all age groups. In the 1990s study, for every 1,000 men aged 70-74, 12.9 went on to develop dementia within a year. In the second study, 20 years later, that figure had dropped to only 8.7 men. For men aged 65-69 the rate of new cases had more than halved between the two studies. © 2016 Guardian News and Media Limited
Link ID: 22122 - Posted: 04.20.2016
Ian Sample Science editor The subtle impact of genetics on the age at which people lose their virginity has been teased apart by scientists and shown to have an effect on how well people fare at school. Though mostly driven by upbringing and peer behaviour, a person’s age when they first have sex is also shaped by biological factors where genes have a role to play. Researchers found that differences in DNA could account for a quarter of the variation in the age at which people lost their virginity, with other factors, among them religious beliefs, family background and peer pressure, making up the rest. Genes influence academic ability across all subjects, latest study shows Read more “We were able to calculate for the first time that there is a heritable component to age at first sex, and the heritability is about 25%, so one quarter nature, three quarters nurture,” said John Perry, an expert in reproductive ageing and related health conditions at Cambridge University. Among 38 sections of DNA found to affect the age at which people first had sex were genes that drive reproductive biology, such as the release of sex hormones and the age of puberty. Still others were found that appear to affect behaviour, personality and appearance. A variant of one of the genes, named CADM2, linked an early start to one’s sex life with risk-taking behaviour and having a large number of children. A version of another gene, MSRA, found in people who lost their virginity later than average, was linked to irritability. © 2016 Guardian News and Media Limited
Scientists believe injections of a natural protein may lessen the symptoms and progress of Alzheimer's dementia after promising early trials in mice. The treatment - IL 33 - appeared to improve memory and help clear and prevent brain deposits similar to those seen in people with Alzheimer's. Tentative human studies of the treatment will soon begin, but experts say it will take many years to know if it could help patients in real life. The work is published in PNAS journal. Interleukin 33, or IL 33 for short, is made by the body as part of its immune defence against infection and disease, particularly within the brain and spinal cord. And patients with Alzheimer's have been found to have lower amounts of IL 33 in their brains than healthy adults. The researchers from the University of Glasgow and the Hong Kong University of Science and Technology tested what effect a boost of IL 33 might have on mice bred to have brain changes akin to Alzheimer's. The rodents rapidly improved their memory and cognitive function to that of the age-matched normal mice within a week of having the injections. Prof Eddy Liew, who led the work at the University of Glasgow, is excited but cautious about his findings. "Exciting as it is, there is some distance between laboratory findings and clinical applications. There have been enough false 'breakthroughs' in the medical field to caution us not to hold our breath until rigorous clinical trials have been done." © 2016 BBC.
Link ID: 22115 - Posted: 04.19.2016
For the first time, scientists have scanned the brains of subjects taking LSD, and found that the LSD state mimics that of infants. NPR's Rachel Martin speaks with researcher Robin Carhart-Harris. RACHEL MARTIN, HOST: Picture yourself in a boat on a river with tangerine trees and marmalade skies. Now picture yourself as a baby. You gaze up at your mother. She's got those kaleidoscope eyes. Pretty trippy, right? Turns out in a new study of brain scans, that the minds of people on LSD function in a similar way to babies' brains. Dr. Robin Carhart-Harris from Imperial College London's Center for Neuropsychopharmacology joins us from the studios of the BBC to talk about this study. So I understand this was the first time that brain scans like this have ever been done, looking specifically at the brains of people who have used LSD. How much LSD had your subjects taken? I mean, what were the prerequisites for a brain that you were going to scan? CARHART-HARRIS: Yeah, so they had to have had at least one experience with a psychedelic drug. So that includes LSD. It also includes magic mushrooms, other concoctions like ayahuasca, which is an Amazonian brew that has psychedelic properties. We gave them a moderate dose of LSD, roughly equivalent to what you might call a hit of LSD or one blotter of LSD if it was to be taken recreationally. MARTIN: So what kind of vetting did you have to do of the participants in your study because we should say different people respond to LSD in different ways? There are risks associated with this drug. CARHART-HARRIS: That's quite right. All drugs have risks, and LSD's no exception. One of the risks is that you might recruit someone who has a psychological vulnerability. So we're very, very careful when we recruit our volunteers to ensure that they have a solid mental health background. They don't have any personal or family history of any psychotic disorders - so those are things like schizophrenia. We have a psychiatrist assess them. We also evaluate their health. So they are very thoroughly screened. © 2016 npr
Dr. Perri Klass First of all, nobody takes a small child on an airplane for the fun of it. I have been there and I know. Don’t get me wrong, I’m no airplane saint; you won’t generally catch me offering to hold someone else’s kid, or making friends around the seatback. I don’t usually admit to being a pediatrician, for fear of hearing a medical saga. But I have put in my time on airplanes with my own infants and toddlers and small children, and I certainly know how it feels. Probably the best thing that can be said for traveling with young children is that it teaches you to appreciate traveling without them, however puzzling the inflight announcements, however long the delays, however tightly spaced the seats. I did enough economy-class traveling with children while my own were young that my reflexive reaction to all flight cancellations, turbulence or the moment when the person in front of me reclines the seat very suddenly, knocking my laptop closed, is now: At least I don’t have a small child with me – thank heavens. Babies do not cry on airplanes for the fun of it either. Nor do they cry, by and large, to let you know that their parents are neglectful or callous. They cry for infant versions of the same reasons that adults snap at one another about reclining seats, or elbow each other with quiet savagery over the armrest. They cry because their ears hurt and they’re being made to stay in a certain position when they don’t want to or the air smells strange and the noises are loud, or their stomachs feel upset or the day has been too long and they still aren’t there yet or they’re just plain cranky. As are we all. Crying is an evolutionary strategy to summon adult aid; over millennia, crying has probably evolved to be hard to ignore. I don’t know if it’s any comfort, but when you’re the parent with the crying baby, it doesn’t particularly help to be an expert. “I remember one flight where my daughter screamed the whole way and kept trying to get out of her seatbelt,” said my old friend, Dr. Elizabeth Barnett, a professor of pediatrics at Boston University and a travel medicine specialist. “As a parent, you feel two things — you’re in distress because you’re trying to comfort your child and not succeeding, so you feel bad for your child, and you also feel guilty because you know your child is disturbing everybody else.” © 2016 The New York Times Company
By Jordana Cepelewicz The brain relies on a system of chemical messengers, known as neurotransmitters, to carry missives from cell to cell. When all is well, these communications enable the brain to coordinate various functions, from complex thought to quick, knee-jerk reactions—but when the system is out of whack, serious disease or disorder can ensue. A team of researchers at the Technical University of Denmark (D.T.U.) and University of Oxford have for the first time identified the molecular structure of dopamine beta-hydroxylase (DBH), the enzyme that controls the conversion between dopamine and norepinephrine, two major neurotransmitters. Understanding the crystal structure of the enzyme could provide an ideal target for drug development. Dopamine and norepinephrine play key roles in many brain functions such as learning, memory, movement and the fight-or-flight response. Imbalances in the levels of these neurotransmitters—and the role DBH plays in regulating them—have been implicated in a wide range of disorders, including hypertension, congestive heart failure, anxiety, depression, post-traumatic stress disorder, Alzheimer’s, schizophrenia, Parkinson’s and even cocaine addiction. DBH has long intrigued biochemists but it has been challenging to perform the analyses needed to determine the protein’s structure. “This enzyme has been particularly difficult,” says Hans Christensen, a chemist at D.T.U. and the study’s lead researcher. “We tried many different expression systems before we finally succeeded. Now that we have the structure it is clear why—[it] is very intricate, with different parts of the enzyme interacting very tightly.” © 2016 Scientific American,
By Roni Caryn Rabin Alzheimer’s disease is a progressive brain disorder that causes dementia, destroying memory, cognitive skills, the ability to care for oneself, speak and walk, said Ruth Drew, director of family and information services at the Alzheimer’s Association. “And since the brain affects everything, Alzheimer’s ultimately affects everything,” she said, “including the ability to swallow, cough and breathe.” Once patients reach the advanced stages of Alzheimer’s, they may stop eating and become weak and susceptible to infections, said Dr. Jason Karlawish, a professor of medicine at the University of Pennsylvania. Unable to swallow or cough, they are at high risk of choking, aspirating food particles or water into the lungs and developing pneumonia, which is often the immediate cause of death, he said. “You see a general decline in the contribution the brain makes, not just in thinking, but in maintaining the body’s homeostasis,” Dr. Karlawish said. Using a feeding tube to nourish patients and hospitalizing them for infections does not significantly extend life at the advanced stages of the disease and is discouraged because it can prolong suffering with no hope of recovery, he said. Alzheimer's is the sixth leading cause of death in the United States, according to the Centers for Disease Control and Prevention, but that figure may underestimate the actual number of cases, Dr. Karlawish said, since some deaths may be attributed to other causes like pneumonia. © 2016 The New York Times Company
Link ID: 22071 - Posted: 04.06.2016
Mo Costandi This spectacular image – which took the best part of a year to create – shows the fine structure of a nerve terminal at high resolution, revealing, for the very first time, an intricate network of fine filaments that controls the movements of synaptic vesicles. The brain is soft and wet, with the consistency of a lump of jelly. Yet, it is the most complex and highly organized structure that we know of, containing hundreds of billions of neurons and glial cells, and something on the order of one quadrillion synaptic connections, all of which are arranged in a very specific manner. This high degree of specificity extends down to the deepest levels of brain organization. Just beneath the membrane at the nerve terminal, synaptic vesicles store neurotransmitter molecules, and await the arrival of a nervous impulse, whereupon they fuse with the membrane and release their contents into the synaptic cleft, the miniscule gap at the junction between nerve cells, and diffuse across it to bind to receptor protein molecules embedded at the surface of the partner cell. 3D model of a nerve terminal in atomic detail The process of neurotransmitter release is tightly orchestrated. Ready vesicles are ‘docked’ in the ‘active zone’ lying beneath the cell membrane, and are depleted when they fuse with the membrane, only to be replenished from a reservoir of pre-prepared vesicles located further inside the cell. Spent vesicles are quickly pulled back out of the membrane, reformed, refilled with neurotransmitter molecules, and then returned to the reservoir, so that they can be shuttled into the active zone when needed. An individual nerve cell may use up hundreds, or perhaps thousands, of vesicles every second, and so this recycling process occurs continuously to maintain the signalling between nerve cells. © 2016 Guardian News and Media Limited
Keyword: Development of the Brain
Link ID: 22067 - Posted: 04.04.2016
By DONALD G. McNEIL Jr The World Health Organization said on Thursday that there is “strong scientific consensus” that Zika virus is a cause of microcephaly, unusually small heads with brain damage in infants, as well as other neurological disorders. Yet a surge in microcephaly has been reported only in Brazil; a small increase was reported in French Polynesia, and a cluster of 32 cases is now under investigation in Colombia. For proof of the connection between infection with the virus and birth defects, scientists are waiting for the results of a large study of 5,000 pregnant women, most of them in Colombia. Women with past Zika infections will be compared with similar women without infections to see if they have more microcephalic children. The epidemic peaked in Colombia in early February, according to the W.H.O. Most of the women in the study are due to give birth in May and June. Virtually all public health agencies already believe the virus is to blame for these birth defects and are giving medical advice based on that assumption. Here are the lines of evidence they cite. As early as last August, hospitals in northeast Brazil realized that something unheard of was happening: Neonatal wards that normally saw one or two microcephalic babies a year were seeing five or more at the same time. Doctors learned from the mothers that many of them had had Zika symptoms months earlier. © 2016 The New York Times Company
Keyword: Development of the Brain
Link ID: 22065 - Posted: 04.04.2016
The mystery is starting to untangle. It has long been known that twisted fibres of a protein called tau collect in the brain cells of people with Alzheimer’s, but their exact role in the disease is unclear. Now a study in mice has shown how tau interferes with the strengthening of connections between neurons – the key mechanism by which we form memories. In healthy cells, the tau protein helps to stabilise microtubules that act as rails for transporting materials around the cell. In people with Alzheimer’s, these proteins become toxic, but an important unanswered question is what forms of tau are toxic: the tangles may not be the whole story. In the new study, Li Gan and her colleagues at the Gladstone Institute of Neurological Disease in San Francisco found that the brains of those with Alzheimer’s have high levels of tau with a particular modification, called acetylated tau. They then looked at what acetylated tau does in a mouse model of Alzheimer’s, finding that it accumulates at synapses – the connections between neurons. When we form memories, synapses become strengthened through extra receptors inserted into the cell membranes, and this heightens their response. But acetylated tau depletes another protein called KIBRA, which is essential for this synapse-strengthening mechanism. “We’re excited because we think we now have a handle on the link between tau and memory,” says Gan. “We’re also cautious because we know this may not be the only link. It’s still early days in understanding the mechanism.” © Copyright Reed Business Information Ltd.
By Emily Underwood More than 99% of clinical trials for Alzheimer’s drugs have failed, leading many to wonder whether pharmaceutical companies have gone after the wrong targets. Now, research in mice points to a potential new target: a developmental process gone awry, which causes some immune cells to feast on the connections between neurons. “It is beautiful new work,” which “brings into light what’s happening in the early stage of the disease,” says Jonathan Kipnis, a neuroscientist at the University of Virginia School of Medicine in Charlottesville. Most new Alzheimer’s drugs aim to eliminate β amyloid, a protein that forms telltale sticky plaques around neurons in people with the disease. Those with Alzheimer’s tend to have more of these deposits in their brains than do healthy people, yet more plaques don’t always mean more severe symptoms such as memory loss or poor attention, says Beth Stevens of Boston Children’s Hospital, who led the new work. What does track well with the cognitive decline seen in Alzheimer’s disease—at least in mice that carry genes that confer high risk for the condition in people—is a marked loss of synapses, particularly in brain regions key to memory, Stevens says. These junctions between nerve cells are where neurotransmitters are released to spark the brain’s electrical activity. Stevens has spent much of her career studying a normal immune mechanism that prunes weak or unnecessary synapses as the brain matures from the womb through adolescence, allowing more important connections to become stronger. In this process, a protein called C1q sets off a series of chemical reactions that ultimately mark a synapse for destruction. After a synapse has been “tagged,” immune cells called microglia—the brain’s trash disposal service—know to “eat” it, Stevens says. © 2016 American Association for the Advancement of Science