Depression, Behavioral Changes May Precede Memory Loss in Alzheimer’s

(Washington University, St. Louis) Depression and behavioral changes may occur before memory declines in people who will go on to develop Alzheimer’s disease, according to new research at Washington University School of Medicine in St. Louis.

Researchers have known that many people with Alzheimer’s experience depression, irritability, apathy and appetite loss but had not recognized how early these symptoms appear. Pinpointing the origins of these symptoms could be important to fully understanding Alzheimer’s effects on the brain and finding ways to counteract them.

“There has been conflicting evidence on the relationship between Alzheimer’s and depression,” said senior author Catherine M. Roe, PhD, assistant professor of neurology.

“We still don’t know whether some of these symptoms, such as irritability and sadness, are due to people realizing on some level that they are having problems with memory and thinking, or whether these symptoms are caused directly by Alzheimer’s effects on the brain.”

The study appears Jan. 14 in Neurology.

Roe and her colleagues at the university’s Charles F. and Joanne Knight Alzheimer’s Disease Research Center analyzed data on 2,416 people ages 50 and older. Scientists regularly evaluated the participants for up to seven years, including how they performed in extensive tests of mental function and psychological health.

All of the participants were cognitively normal at the start, but over the course of the study, 1,218 of them developed dementia. 

Those who developed dementia during the study were more likely to have mood and behavioral changes first. For example, four years into the study, 30 percent of those who would go on to develop dementia had developed depression.

In comparison, after the same period of time, only 15 percent of those who did not develop dementia during the study had become depressed. In addition, those who would go on to develop dementia were more than 12 times as likely to have delusions than those who did not develop dementia. 

Alzheimer’s researchers have been working to develop markers they can use to diagnose disease before the onset of dementia. The hope is to begin treating the condition before patients develop dementia.

However, Roe cautioned that the mood changes will not work well as markers in this regard until researchers better understand how these changes are connected to the disease.

Citation

http://genetics.wustl.edu/blog/depression-behavioral-changes-may-precede-memory-loss-in-alzheimers/

Journal Reference:

Masters MC, Morris JC, Roe CM. “Noncognitive” symptoms of early Alzheimer disease. Neurology, January 2015 DOI: 10.1212/WNL.0000000000001238 1526-632X

Copyright 2015 Washington University Genetics

 

Alzheimer’s Disease Knowledge Test: How Much Do You Know?

Dear Readers:

In 2009, several scientists from U.S. Universities developed the Alzheimer’s Disease Knowledge Scale (ASKS) to assess knowledge of Alzheimer’s disease among lay people, patients, caregivers, and professionals.

The test is 30-item, true/false scale that takes approximately 5–10 min to complete. It covers risk factors, assessment and diagnosis, symptoms, course, life impact, caregiving, and treatment and management.

Here is the test:

ADKS

Please download the file, print the test, and check your knowledge. The better informed you are, the better a caregiver you will be!

Here is the test with the answers:

ADKS with Answers and Citations

Let me know what you think.

Best, Jennifer

Citation

Brian D. Carpenter, PhD, Steve Balsis, MA, Poorni G. Otilingam, MPH, MA, Priya K. Hanson, MMFT, and Margaret Gatz, PhD. The Alzheimer’s Disease Knowledge Scale: Development and Psychometric Properties. Gerontologist. Apr 2009; 49(2): 236–247. Published online Mar 25, 2009. doi:  10.1093/geront/gnp023

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2667675/

National Center for Biotechnology Information, U.S. National Library of Medicine

 

Alzheimer’s Disease: Why Get Checked?

(Alzheimer’s Association) If you notice any of the 10 Warning Signs of Alzheimer’s in yourself or someone you know, don’t ignore them. Schedule an appointment with your doctor.

With early detection, you can:

Get the maximum benefit from available treatments  You can explore treatments that may provide some relief of symptoms and help you maintain a level of independence longer. You may also increase your chances of participating in clinical drug trials that help advance research.
Learn more about treatments. 
Learn more about clinical studies.

“It took my mother having a stress-related heart attack before we quit dismissing my father’s progressing dementia to ‘senior moments’ and got him a proper diagnosis of Alzheimer’s. Had we paid attention to the warning signs of this disease, a lot of prevention could have been in place.”
– Brent

Have more time to plan for the future  A diagnosis of Alzheimer’s allows you to take part in decisions about care, transportation, living options, financial and legal matters. You can also participate in building the right care team and social support network. 

Learn more about planning ahead.
Learn how to get a personalized action plan by using Alzheimer’s Navigator.

Help for you and your loved ones  Care and support services are available, making it easier for you and your family to live the best life possible with Alzheimer’s or dementia. 
Learn how the Alzheimer’s Association helps families.
Learn how you can find listings of local Alzheimer’s resources, community programs and services by using Community Resource Finder.

Additional information:

When you see your doctor

Your doctor will evaluate your overall health and identify any conditions that could affect how well your mind is working. Your doctor may refer you to a specialist such as a:

  • Neurologist – specializes in diseases of the brain and nervous system
  • Psychiatrist – specializes in disorders that affect mood or the way the mind works
  • Psychologist – has special training in testing memory and other mental functions
  • Geriatrician – specializes in the care of older adults and Alzheimer’s disease

Learn more about diagnosing Alzheimer’s.
Learn more about different types of dementia.

Citation

http://www.alz.org/alzheimers_disease_why_get_checked.asp

Copyright © 2015  Alzheimer’s Association®. All rights reserved.

 

Why Is Sleep Important?

(National Heart, Lung, and Blood Institute) Sleep plays a vital role in good health and well-being throughout your life. Getting enough quality sleep at the right times can help protect your mental health, physical health, quality of life, and safety.

sleepThe way you feel while you’re awake depends in part on what happens while you’re sleeping. During sleep, your body is working to support healthy brain function and maintain your physical health. In children and teens, sleep also helps support growth and development.

The damage from sleep deficiency can occur in an instant (such as a car crash), or it can harm you over time. For example, ongoing sleep deficiency can raise your risk for some chronic health problems. It also can affect how well you think, react, work, learn, and get along with others.

Healthy Brain Function and Emotional Well-Being

Sleep helps your brain work properly. While you’re sleeping, your brain is preparing for the next day. It’s forming new pathways to help you learn and remember information.

Studies show that a good night’s sleep improves learning. Whether you’re learning math, how to play the piano, how to perfect your golf swing, or how to drive a car, sleep helps enhance your learning and problem-solving skills. Sleep also helps you pay attention, make decisions, and be creative.

Studies also show that sleep deficiency alters activity in some parts of the brain. If you’re sleep deficient, you may have trouble making decisions, solving problems, controlling your emotions and behavior, and coping with change. Sleep deficiency also has been linked to depression, suicide, and risk-taking behavior.

Children and teens who are sleep deficient may have problems getting along with others. They may feel angry and impulsive, have mood swings, feel sad or depressed, or lack motivation. They also may have problems paying attention, and they may get lower grades and feel stressed.

Physical Health

Sleep plays an important role in your physical health. For example, sleep is involved in healing and repair of your heart and blood vessels. Ongoing sleep deficiency is linked to an increased risk of heart disease, kidney disease, high blood pressure, diabetes, and stroke.

Sleep deficiency also increases the risk of obesity. For example, one study of teenagers showed that with each hour of sleep lost, the odds of becoming obese went up. Sleep deficiency increases the risk of obesity in other age groups as well.

Sleep helps maintain a healthy balance of the hormones that make you feel hungry (ghrelin) or full (leptin). When you don’t get enough sleep, your level of ghrelin goes up and your level of leptin goes down. This makes you feel hungrier than when you’re well-rested.

Sleep also affects how your body reacts to insulin, the hormone that controls your blood glucose (sugar) level. Sleep deficiency results in a higher than normal blood sugar level, which may increase your risk for diabetes.

Sleep also supports healthy growth and development. Deep sleep triggers the body to release the hormone that promotes normal growth in children and teens. This hormone also boosts muscle mass and helps repair cells and tissues in children, teens, and adults. Sleep also plays a role in puberty and fertility.

Your immune system relies on sleep to stay healthy. This system defends your body against foreign or harmful substances. Ongoing sleep deficiency can change the way in which your immune system responds. For example, if you’re sleep deficient, you may have trouble fighting common infections.

Daytime Performance and Safety

Getting enough quality sleep at the right times helps you function well throughout the day. People who are sleep deficient are less productive at work and school. They take longer to finish tasks, have a slower reaction time, and make more mistakes.

After several nights of losing sleep—even a loss of just 1–2 hours per night—your ability to function suffers as if you haven’t slept at all for a day or two.

Lack of sleep also may lead to microsleep. Microsleep refers to brief moments of sleep that occur when you’re normally awake.

You can’t control microsleep, and you might not be aware of it. For example, have you ever driven somewhere and then not remembered part of the trip? If so, you may have experienced microsleep.

sleep2Even if you’re not driving, microsleep can affect how you function. If you’re listening to a lecture, for example, you might miss some of the information or feel like you don’t understand the point. In reality, though, you may have slept through part of the lecture and not been aware of it.

Some people aren’t aware of the risks of sleep deficiency. In fact, they may not even realize that they’re sleep deficient. Even with limited or poor-quality sleep, they may still think that they can function well.

For example, drowsy drivers may feel capable of driving. Yet, studies show that sleep deficiency harms your driving ability as much as, or more than, being drunk. It’s estimated that driver sleepiness is a factor in about 100,000 car accidents each year, resulting in about 1,500 deaths.

Drivers aren’t the only ones affected by sleep deficiency. It can affect people in all lines of work, including health care workers, pilots, students, lawyers, mechanics, and assembly line workers.

As a result, sleep deficiency is not only harmful on a personal level, but it also can cause large-scale damage. For example, sleep deficiency has played a role in human errors linked to tragic accidents, such as nuclear reactor meltdowns, grounding of large ships, and aviation accidents.

How Much Sleep is Enough?

The amount of sleep you need each day will change over the course of your life. Although sleep needs vary from person to person, the chart below shows general recommendations for different age groups.

Age Recommended Amount of Sleep
Newborns 16–18 hours a day
Preschool-aged children 11–12 hours a day
School-aged children At least 10 hours a day
Teens 9–10 hours a day
Adults (including the elderly) 7–8 hours a day

 

If you routinely lose sleep or choose to sleep less than needed, the sleep loss adds up. The total sleep lost is called your sleep debt. For example, if you lose 2 hours of sleep each night, you’ll have a sleep debt of 14 hours after a week.

Some people nap as a way to deal with sleepiness. Naps may provide a short-term boost in alertness and performance. However, napping doesn’t provide all of the other benefits of night-time sleep. Thus, you can’t really make up for lost sleep.

Some people sleep more on their days off than on work days. They also may go to bed later and get up later on days off.

Sleeping more on days off might be a sign that you aren’t getting enough sleep. Although extra sleep on days off might help you feel better, it can upset your body’s sleep–wake rhythm.

Bad sleep habits and long-term sleep loss will affect your health. If you’re worried about whether you’re getting enough sleep, try using a sleep diary for a couple of weeks.

sleep3Write down how much you sleep each night, how alert and rested you feel in the morning, and how sleepy you feel during the day. Show the results to your doctor and talk about how you can improve your sleep. You can find a sample sleep diary in the National Heart, Lung, and Blood Institute’s “Your Guide to Healthy Sleep.”

Sleeping when your body is ready to sleep also is very important. Sleep deficiency can affect people even when they sleep the total number of hours recommended for their age group.

For example, people whose sleep is out of sync with their body clocks (such as shift workers) or routinely interrupted (such as caregivers or emergency responders) might need to pay special attention to their sleep needs.

If your job or daily routine limits your ability to get enough sleep or sleep at the right times, talk with your doctor. You also should talk with your doctor if you sleep more than 8 hours a night, but don’t feel well rested. You may have a sleep disorder or other health problem.

Strategies for Getting Enough Sleep

You can take steps to improve your sleep habits. First, make sure that you allow yourself enough time to sleep. With enough sleep each night, you may find that you’re happier and more productive during the day.

Sleep often is the first thing that busy people squeeze out of their schedules. Making time to sleep will help you protect your health and well-being now and in the future.

To improve your sleep habits, it also may help to:

  • Go to bed and wake up at the same time every day. For children, have a set bedtime and a bedtime routine. Don’t use the child’s bedroom for timeouts or punishment.
  • Try to keep the same sleep schedule on weeknights and weekends. Limit the difference to no more than about an hour. Staying up late and sleeping in late on weekends can disrupt your body clock’s sleep–wake rhythm.
  • Use the hour before bed for quiet time. Avoid strenuous exercise and bright artificial light, such as from a TV or computer screen. The light may signal the brain that it’s time to be awake.
  • Avoid heavy and/or large meals within a couple hours of bedtime. (Having a light snack is okay.) Also, avoid alcoholic drinks before bed.
  • Avoid nicotine (for example, cigarettes) and caffeine (including caffeinated soda, coffee, tea, and chocolate). Nicotine and caffeine are stimulants, and both substances can interfere with sleep. The effects of caffeine can last as long as 8 hours. So, a cup of coffee in the late afternoon can make it hard for you to fall asleep at night.
  • Spend time outside every day (when possible) and be physically active.
  • Keep your bedroom quiet, cool, and dark (a dim night light is fine, if needed).
  • Take a hot bath or use relaxation techniques before bed.

Napping during the day may provide a boost in alertness and performance. However, if you have trouble falling asleep at night, limit naps or take them earlier in the afternoon. Adults should nap for no more than 20 minutes.

Napping in preschool-aged children is normal and promotes healthy growth and development.

For more information about healthy sleep habits, go to the National Heart, Lung, and Blood Institute’s “Your Guide to Healthy Sleep.”

Strategies for Special Groups

Some people have schedules that conflict with their internal body clocks. For example, shift workers and teens who have early school schedules may have trouble getting enough sleep. This can affect how they feel mentally, physically, and emotionally.

If you’re a shift worker, you may find it helpful to:

  • Take naps and increase the amount of time available for sleep
  • Keep the lights bright at work
  • Limit shift changes so your body clock can adjust
  • Limit caffeine use to the first part of your shift
  • Remove sound and light distractions in your bedroom during daytime sleep (for example, use light-blocking curtains)

If you’re still not able to fall asleep during the day or have problems adapting to a shift-work schedule, talk with your doctor about other options to help you sleep.

When possible, employers and schools might find it helpful to consider options to address issues related to sleep deficiency.

Citation

http://www.nhlbi.nih.gov/health/health-topics/topics/sdd/why

National Institutes of Health, Department of Health and Human Services

 

Curcumin’s Ability to Fight Alzheimer’s Studied

(Vanderbilt University Medical Center) One of the most promising new treatments for Alzheimer’s disease may already be in your kitchen. Curcumin, a natural product found in the spice turmeric, has been used by many Asian cultures for centuries, and a new study indicates a close chemical analog of curcumin has properties that may make it useful as a treatment for the brain disease.

CurcuminVanderbilt investigators are studying curcumin, which is found in the spice turmeric, as a treatment for Alzheimer’s disease.

“Curcumin has demonstrated ability to enter the brain, bind and destroy the beta-amyloid plaques present in Alzheimer’s with reduced toxicity,”

said Wellington Pham, Ph.D., assistant professor of Radiology and Radiological Sciences and Biomedical Engineering at Vanderbilt and senior author of the study, published recently in the Journal of Alzheimer’s Disease.

Accumulation and aggregation of protein fragments, known as beta-amyloid, drives the irreversible loss of neurons in Alzheimer’s disease.

Developing small molecules to reduce this accumulation or promote its demolition is crucial, but the ability of these small molecules to cross the blood-brain barrier has been a restricting factor for drug delivery into the brain.

Pham and colleagues at Shiga University of Medical Science in Otsu, Japan, developed a new strategy to deliver a molecule similar to curcumin more effectively to the brain.

“One of the difficulties in the treatment of Alzheimer’s disease is how to deliver drugs across the blood brain barrier,” he said.

“Our body has designed this barrier to protect the brain from any toxic molecules that can cross into the brain and harm neurons.

“But it is also a natural barrier for molecules designed for disease-modifying therapy,” Pham said.

To work around the problems of giving the drug intravenously, the researchers decided to develop an atomizer to generate a curcumin aerosol. The Japanese researchers developed a molecule similar to curcumin, FMeC1, which was the one actually used in this study.

“The advantage of the FMeC1 is that it is a perfluoro compound, which can be tracked by the biodistribution in the brain noninvasively using magnetic resonance imaging. Curcumin is a very simple chemical structure, so it is not expensive to generate the analog,” Pham said.

“In this way the drug can be breathed in and delivered to the brain,” he said, noting that nebulizers are out in the market already, and are relatively inexpensive.

“In this paper we also showed that delivery to the cortex and hippocampal areas is more efficient using aerosolized curcumin than intravenous injection in a transgenic mouse model of Alzheimer’s disease,” Pham said.

Citation

Patricia Jumbo-Lucioni

http://news.vanderbilt.edu/2015/01/curcumin%E2%80%99s-ability-to-fight-alzheimer-studied/

© 2015 Vanderbilt University

 

University of Rochester’s Alzheimer’s Agitation Study Among Top 10 of 2014

(University of Rochester) The American Academy of Neurology (AAN), the world’s largest professional association of neurologists, has included a UR Medicine study among its picks for the most revolutionary research of 2014.  The study, which originally appeared in the Journal of the American Medical Association (JAMA), found that a high dose of a common antidepressant drug (citalopram) significantly reduced agitation in Alzheimer’s disease patients and helped alleviate caregiver distress.

“While the study on citalopram identified issues with side effects, given the lack of efficacious treatments for patients with dementia and agitation, citalopram and (related medications) are now treatment options for this group of patients that is so difficult to help,”

the Academy noted in its official publication, Neurology Today. The journal’s editorial advisory board selected the studies included on the 2014 list.

“Our Alzheimer’s Disease Care, Research and Education (AD-CARE) program is on the leading edge of research in the development and testing of novel therapeutics that, in time, will defeat this disease,” says Yeates Conwell, M.D., director of the University of Rochester Medical Center’s Office for Aging Research and Health Services. 

“But our researchers are also leaders in generating knowledge about how to treat older adults and their families today.”

Agitation can be one of the most heartbreaking symptoms of Alzheimer’s disease, and it is one of the most common reasons Alzheimer’s patients are moved out of their homes into higher levels of care.  Caregivers watch as their loved ones become increasingly short-tempered, physically restless, resistant to help, or even verbally and physically abusive.  Treatment options are very limited.

“The citalopram study produced a drop of hope in a field that has seen a sea of negative study results,” says Anton P. Porsteinsson, M.D., the Willam B. and Sheila Konar Professor  of Psychiatry and lead author of the citalopram study.

“It is an honor to have our efforts recognized by Neurology Today, and it will inspire us as we continue this important work.”

UR Medicine is one of the nation’s premier Alzheimer’s disease clinical research sites. Scientists are conducting numerous studies into experimental drugs that are designed to treat or prevent this devastating illness.  For more information, visit the AD-CARE web site.

Citation

http://www.urmc.rochester.edu/news/story/index.cfm?id=4231

© 2015 University of Rochester Medical Center

 

A New Opportunity in the Fight Against Alzheimer’s

(Alzheimer’s Association) This week marks the beginning of the 114th Congress. Engaging newly elected officials in the fight against Alzheimer’s disease — the nation’s sixth-leading cause of death and the most expensive condition in the United States — is crucial, as is ensuring that our current supporters in the federal government stay the course.

By attending the 2015 Alzheimer’s Association Advocacy Forum, you can directly tell members of Congress how important it is that they provide the research funding necessary to reach the National Alzheimer’s Plan’s goal to prevent and effectively treat Alzheimer’s by 2025, as well as the resources necessary to offer care and support to those individuals the disease affects today.

Register now for the 2015 Advocacy Forum.

Alzheimer’s Association Advocacy Forum
March 23-25, 2015
Washington Marriott Wardman Park
Washington, D.C.

Citation

http://www.alz.org/forum/

© 2015 Alzheimer’s Association | www.alz.org | All rights reserved.

 

Blocking Receptor in Brain’s Immune Cells Counters Alzheimer’s in Mice, Stanford Study Finds

(Stanford Medicine) Brain cells called microglia chew up toxic substances and cell debris, calm inflammation and make nerve-cell-nurturing substances. New research shows that keeping them on the job may prevent neurodegeneration.

The mass die-off of nerve cells in the brains of people with Alzheimer’s disease may largely occur because an entirely different class of brain cells, called microglia, begin to fall down on the job, according to a new study by researchers at the Stanford University School of Medicine.

The researchers found that, in mice, blocking the action of a single molecule on the surface of microglia restored the cells’ ability to get the job done — and reversed memory loss and myriad other Alzheimer’s-like features in the animals.

The study, published online Dec. 8 in The Journal of Clinical Investigation, illustrates the importance of microglia and could lead to new ways of warding off the onset of Alzheimer’s disease, which is predicted to afflict 15 million people by mid-century unless some form of cure or prevention is found. The study also may help explain an intriguing association between aspirin and reduced rates of Alzheimer’s.

Microglia, which constitute about 10-15 percent of all the cells in the brain, actually resemble immune cells considerably more than they do nerve cells.

“Microglia are the brain’s beat cops,” said Katrin Andreasson, MD, professor of neurology and neurological sciences and the study’s senior author. “Our experiments show that keeping them on the right track counters memory loss and preserves healthy brain physiology.”

Implicated: a Single Molecule

A microglial cell serves as a front-line sentry, monitoring its surroundings for suspicious activities and materials by probing its local environment. If it spots trouble, it releases substances that recruit other microglia to the scene, said Andreasson. Microglia are tough cops, protecting the brain against invading bacteria and viruses by gobbling them up. They are adept at calming things down, too, clamping down on inflammation if it gets out of hand. They also work as garbage collectors, chewing up dead cells and molecular debris strewn among living cells — including clusters of a protein called A-beta, notorious for aggregating into gummy deposits called Alzheimer’s plaques, the disease’s hallmark anatomical feature.

A-beta, produced throughout the body, is as natural as it is ubiquitous. But when it clumps into soluble clusters consisting of a few molecules, it’s highly toxic to nerve cells. These clusters are believed to play a substantial role in causing Alzheimer’s.

“The microglia are supposed to be, from the get-go, constantly clearing A-beta, as well as keeping a lid on inflammation,” Andreasson said. “If they lose their ability to function, things get out of control. A-beta builds up in the brain, inducing toxic inflammation.”

The Stanford study provides strong evidence that this deterioration in microglial function is driven, in large part, by the heightened signaling activity of a single molecule that sits on the surface of microglial and nerve cells.

Previous work in Andreasson’s lab and other labs has shown that this molecule, a receptor protein called EP2, has a strong potential to cause inflammation when activated by binding to a substance called prostaglandin E2, or PGE2.

“We’d previously observed that if we bioengineered mice so their brain cells lacked this receptor, there was a huge reduction in inflammatory activity in the brain,” she said. But they didn’t know whether nerve cells or microglia were responsible for that inflammatory activity, or what its precise consequences were. So they determined to find out.

Blocking Receptor Preserves Memory

The experiments began in a dish. Isolating viable microglia from the brain is quite difficult. But it’s easy to harvest large numbers of their close cousins, immune cells called macrophages. These cells circulate throughout the body and can be readily obtained from a blood sample. While not carbon copies of one another, microglia and macrophages share numerous genetic, biochemical and behavioral features.

When placed in a dish with soluble A-beta clusters, macrophages drawn from young mice responded calmly, producing recruiting chemicals and not ramping up production of inflammatory molecules. Notably, the output of A-beta-chewing enzymes in these young cells was robust.

But macrophages from older mice acted differently: A-beta’s presence incited a big increase in EP2 activity in these cells, resulting in amped-up output of inflammatory molecules and reduced generation of recruiting chemicals and A-beta-digesting enzymes.

This early hint that age-related changes in EP2 action in microglia might be promoting some of the neuropathological features implicated in Alzheimer’s was borne out in subsequent experiments for which Andreasson’s team used mice genetically predisposed to get the mouse equivalent of Alzheimer’s, as well as otherwise normal mice into whose brains the scientists injected either A-beta or a control solution.

In both groups of mice, the expected deleterious effects on memory and learning didn’t arise if EP2 within microglial cells was absent, as a result of a genetic manipulation. Blocking microglial EP2 activity significantly improved these animals’ performance on two kinds of standard memory tests: one that assesses how quickly a mouse forgets that it has encountered an object before, and another that rates the mouse’s ability to remember where a food reward is in a maze.

Looking Beyond Aspirin

Clearly, knocking out EP2 action in A-beta-provoked microglia benefited memory in mice that had either gradually (the “Alzheimer’s” mice) or suddenly (the brain-injected mice) acquired excessive A-beta in their brains.

Likewise, mouse microglia bioengineered to lack EP2 vastly outperformed unaltered microglia, in A-beta-challenged brains, at such critical tasks as secreting recruiting chemicals and factors beneficial to nerve cells and in producing inflammation-countering, rather than inflammation-spurring, proteins.

Epidemiological reports suggest that the use of nonsteroidal anti-inflammatory drugs, such as aspirin, can prevent the onset of Alzheimer’s — although only if their use is initiated well before any signs of the disorder begin to show up in older people, Andreasson said.

“Once you have any whiff of memory loss, these drugs have no effect,” she said.

NSAIDs’ mainly act by blocking two enzymes called COX-1 and COX-2; these enzymes create a molecule that can be converted to several different substances, including PGE2 — the hormone-like chemical that triggers EP2 action.

Although PGE2 is known to regulate inflammatory changes in the brain, it exercises diverse, useful functions in different tissues throughout the body, from influencing blood pressure to inducing labor.

Complicating matters, PGE2 is just one of five different prostaglandins originating from the precursor molecule produced by COX-1 and COX-2. So aspirin and other COX-1- and COX-2-inhibiting drugs may have myriad effects, not all of them beneficial.

It may turn out that a compound blocking only EP2 activity on microglial cells, or some downstream consequences within microglial cells, would be better-suited for fending off Alzheimer’s without side effects, said Andreasson. Meanwhile, her group is exploring the biological mechanisms via which PE2 signaling pushes microglia over to the dark side.

Former Stanford postdoctoral scholar Jenny Johansson, PhD, is the lead author of the study. Other Stanford co-authors are former graduate student Nathan Woodling, PhD; postdoctoral scholars Siddhita Mhartre, PhD, and Holden Brown, PhD; research associate Xibin Liang, MD, PhD; life-science research assistants Qian Wang and Maharshi Panchal; and undergraduate Taylor Loui.

The study was supported by the National Institutes for Health (grants RO1AG030209, R21AG033914 and NRSA F31AG039195), the Alzheimer’s Association, the Swedish Research Council and the National Science Foundation.

Information about Stanford’s Department of Neurology and Neurological Sciences, which also supported the work, is available at http://www.neurology.stanford.edu.

Citation

Bruce Goldman

http://med.stanford.edu/news/all-news/2014/12/blocking-receptor-in-brains-immune-cells-counters-alzheimers.html

©2015 Stanford Medicine