TAG: "Alzheimer’s"

Lost memories might be able to be restored


UCLA research reveals that memories may not be stored in synapses, as previously thought.

UCLA's David Glanzman with a marine snail. (Photo by Christelle Nahas, UCLA)

By Stuart Wolpert, UCLA

New UCLA research indicates that lost memories can be restored. The findings offer some hope for patients in the early stages of Alzheimer’s disease.

For decades, most neuroscientists have believed that memories are stored at the synapses — the connections between brain cells, or neurons — which are destroyed by Alzheimer’s disease. The new study provides evidence contradicting the idea that long-term memory is stored at synapses.

“Long-term memory is not stored at the synapse,” said David Glanzman, a senior author of the study, and a UCLA professor of integrative biology and physiology and of neurobiology. “That’s a radical idea, but that’s where the evidence leads. The nervous system appears to be able to regenerate lost synaptic connections. If you can restore the synaptic connections, the memory will come back. It won’t be easy, but I believe it’s possible.”

The findings were published recently in eLife, a highly regarded open-access online science journal.

Glanzman’s research team studies a type of marine snail called Aplysia to understand the animal’s learning and memory. The Aplysia displays a defensive response to protect its gill from potential harm, and the researchers are especially interested in its withdrawal reflex and the sensory and motor neurons that produce it.

They enhanced the snail’s withdrawal reflex by giving it several mild electrical shocks on its tail. The enhancement lasts for days after a series of electrical shocks, which indicates the snail’s long-term memory. Glanzman explained that the shock causes the hormone serotonin to be released in the snail’s central nervous system.

Long-term memory is a function of the growth of new synaptic connections caused by the serotonin, said Glanzman, a member of UCLA’s Brain Research Institute. As long-term memories are formed, the brain creates new proteins that are involved in making new synapses. If that process is disrupted — for example by a concussion or other injury — the proteins may not be synthesized and long-term memories cannot form.  (This is why people cannot remember what happened moments before a concussion.)

“If you train an animal on a task, inhibit its ability to produce proteins immediately after training, and then test it 24 hours later, the animal doesn’t remember the training,” Glanzman said.  “However, if you train an animal, wait 24 hours, and then inject a protein synthesis inhibitor in its brain, the animal shows perfectly good memory 24 hours later.  In other words, once memories are formed, if you temporarily disrupt protein synthesis, it doesn’t affect long-term memory. That’s true in the Aplysia and in human’s brains.”  (This explains why people’s older memories typically survive following a concussion.)

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Research on cell biology mystery may reveal root causes of Alzheimer’s


A well-known cellular structure orchestrates how vault nanoparticles naturally form in cells.

In the 1980s, professor Leonard Rome and his then-postdoctoral fellow Nancy Kedersha made a breakthrough in cell biology when they discovered vaults, naturally occurring nanoparticles — of a size measured in nanometers (1 nanometer = 1 billionth of a meter) — that are composed mostly of proteins and number in the thousands inside every cell of the body.

In the decades since, Rome’s team has discovered how to form vaults in the laboratory using the proteins they consist of. While naturally occurring vaults contain other elements, Rome’s team built empty ones, which eventually enabled them to pursue the idea of inserting drug molecules into vaults. Those could then be put in serum, injected into patients, and directed to specific cells where they release the drugs. Thus, vaults are being developed as a highly accurate drug-delivery system that is being commercialized.

But one question that Rome and his team couldn’t answer was how the natural vaults originally formed inside cells. Now Rome and his collaborators at UCLA’s California NanoSystems Institute appear to have solved that mystery.

In a study published online today (Oct. 30) in the journal ACS Nano, Rome’s team, led by first author and postdoctoral scholar Jan Mrazek, report data that suggests that polyribosomes — small molecular machines that read genetic information and form proteins inside cells — work like 3-D printers to both create and link together proteins and correctly form them into vaults. (Watch a brief animated explanation of how it works.)

“This idea needs some further research and confirmation, but it is a very elegant model and we are convinced that it explains how vaults are formed,” said Rome, who is associate director of the California NanoSystems Institute. “If the model is correct, it reveals something new about cell biology — that this polyribosome that has been known for 50 years has a heretofore unknown function. Namely, it orchestrates the assembly of macromolecular complexes such as vaults, and other structures in a cell that are made of multiple proteins.”

Mrazek said that this possible function of polyribosomes may also provide new understanding of protein aggregation, which is a clumping of deformed proteins that happens in such diseases as Alzheimer’s, Parkinson’s and Lou Gehrig’s.

“If a protein is not made correctly, it’s possible that these deformities can alter the guided assembly of macromolecules by the polyribosomes,” Mrazek said. “Once you understand that there is a machine in the cell that directs the formation of these macromolecular complexes, you can see where things might go wrong with that machine. By studying nanotechnology we have revealed something unknown about basic cell biology that might have wider implications.”

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Research to examine whether copper plays role in Alzheimer’s


Do elevated levels of copper in drinking water play a role in the neurodegenerative disease?

UC Merced professor Masashi Kitazawa wants to figure out if any environmental factors increase the risk for developing Alzheimer’s disease – specifically, whether elevated levels of copper in drinking water play a role.

A new $2.6 million, five-year grant from the National Institute of Environmental Health Sciences will fund his research, making what was a side project into a full-blown exploration.

“Copper is an essential metal, but too much will cause problems,” Kitazawa said. “I want to see if the environmentally relevant levels of copper in drinking water will have any impacts on the brain and its functions.”

The EPA sets a limit of 1.3 parts per million of copper per liter of drinking water. In some places, older copper plumbing pipes can be a source of higher levels of copper in water, for example. But water in Merced is well below the EPA’s limit, Kitazawa said.

He hopes five years will be enough time to conduct all the experiments he wants to perform with a research colleague at Tufts University, and analyze all the data. The researchers are looking at two different brain cells to see how copper affects them, and their results could add to the growing body of data about the neurodegenerative disease.

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New front in war on Alzheimer’s


Discovery expands opportunities for therapies to prevent protein-folding diseases.

A cell suffering heat shock is like a country besieged, where attackers first sever lines of communications. The pat-10 gene helps repair communication to allow chaperones to treat misfolded proteins. (Graphic by Andrew Dillin, UC Berkeley)

A surprise discovery that overturns decades of thinking about how the body fixes proteins that come unraveled greatly expands opportunities for therapies to prevent diseases such as Alzheimer’s and Parkinson’s, which have been linked to the accumulation of improperly folded proteins in the brain.

“This finding provides a whole other outlook on protein-folding diseases; a new way to go after them,” said Andrew Dillin, the Thomas and Stacey Siebel Distinguished Chair of Stem Cell Research in the Department of Molecular and Cell Biology and Howard Hughes Medical Institute investigator at the University of California, Berkeley.

Dillin, UC Berkeley postdoctoral fellows Nathan A. Baird and Peter M. Douglas and their colleagues at the University of Michigan, The Scripps Research Institute and Genentech Inc., will publish their results in the Oct. 17 issue of the journal Science.

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UCSF, UC Berkeley scientists team up in new Center for Aging Research


Glenn Center exploring role of decline in protein quality-control in dementias, other illnesses.

Andrew Dillin, UC Berkeley

Researchers at UC San Francisco and UC Berkeley have teamed up to create an innovative, integrated center for research on neurodegenerative diseases. Supported by a $3 million grant from the Glenn Foundation for Medical Research, the new center aims to pave the way to developing novel treatments for diseases such as Alzheimer’s disease and Parkinson’s disease by investigating the many ways that proteins can malfunction within cells.

In particular, the center’s work will focus on a type of protein called the prion, which displays characteristics of infectious agents and is responsible for “mad cow” disease and a related, devastating human brain disorder known as Creutzfeldt-Jakob disease (CJD).

Stanley B. Prusiner, M.D., UCSF professor of neurology, and Andrew Dillin, Ph.D., the Thomas and Stacey Siebel Distinguished Chair of Stem Cell Research at UC Berkeley and a Howard Hughes Medical Institute investigator, will co-direct the new inter-campus program, known as the Paul F. Glenn Center for Aging Research. Ten additional researchers from UCSF and 13 from UC Berkeley will contribute to the center’s work, with more recruitments to come.

Stanley Prusiner, UC San Francisco

“The Glenn Foundation is pleased to welcome UCSF and UC Berkeley to the Glenn Consortium for Research in Aging,” said Mark R. Collins, president of the Glenn Foundation for Medical Research, which is based in Santa Barbara. “I had the pleasure to work with Dr. Dillin previously, when he led the Glenn Center for Aging Research at the Salk Institute for Biological Sciences prior to moving to UC Berkeley. I’ve known Dr. Prusiner and followed his work for many years and it is a propitious time for us to assist these two leaders in biological research to discover treatments for age-related neurodegenerative disease.”

In 1997, Prusiner, director of UCSF’s Institute for Neurodegenerative Diseases, received the Nobel Prize in Physiology or Medicine for his discovery of prions, which he demonstrated were an abnormally folded form of normal proteins that set up a template for replication in the brain. According to Prusiner, recent work provides persuasive evidence that, in addition to mad cow disease and CJD, many common neurodegenerative diseases, including Alzheimer’s and Parkinson’s, are caused by abnormally folded forms of normal proteins functioning as prions.

Dillin agrees that prions are ideal targets for research and novel therapeutic approaches. “The Glenn Foundation’s confidence to support our hypothesis is greatly appreciated,” he said, adding that the combination of UCSF’s medical mission with the strong basic research traditions of both campuses will make the new Glenn Center’s work uniquely powerful.

Proteins are crucial for many of a cell’s normal functions, but as people age, cells’ quality-control mechanisms become less efficient. Normally these systems ensure that proteins are properly formed, and target badly formed or “worn-out” proteins for destruction. But as the effectiveness of cellular quality control wanes over time, improperly formed proteins, including prions, can begin to accumulate.

Badly formed proteins, called “misfolded” by biologists, cannot carry out their required functions and, even worse, they can stick to one another and to other cellular components, sometimes leading to devastating physiological consequences. Prions are particularly problematic because they can act like a template, converting properly formed proteins into additional prions, essentially spreading protein misfolding like an infection.

Seeking ways to counteract the accumulation of misfolded proteins, the new Glenn Center’s researchers will investigate the many cellular quality-control mechanisms that act throughout a protein’s lifetime, from when proteins are first made, to the interactions that help them reach their proper functional state, to the transport processes that take them to their final destinations, to their ultimate degradation when they can no longer serve their purpose.

Together, the UCSF and UC Berkeley researchers affiliated with the center have complementary expertise in all of these areas, and the center’s ultimate goal is to develop new anti-prion drugs, Dillin said. “At Berkeley, we aim to build the basic scientific knowledge to leverage clinical and therapeutic discoveries at UCSF.”

According to Prusiner, “the newest research indicates that Alzheimer’s alone kills as many people every year as cancer does, but it only receives one-tenth of the funding that we dedicate to cancer research. We are grateful to The Glenn Foundation for their support in the battle against neurodegenerative diseases.”

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Memory loss associated with Alzheimer’s is reversed for first time


Small trial by UCLA, Buck Institute succeeds using ‘systems approach’ to memory disorders.

Patient 1 had two years of progressive memory loss. She was considering quitting her job, which involved analyzing data and writing reports, she got disoriented driving, and she mixed up the names of her pets.

Patient 2 kept forgetting once-familiar faces at work, forgot his gym locker combination and had to have his assistants constantly remind him of his work schedule.

Patient 3’s memory was so bad that she used an iPad to record everything, then forgot her password. Her children noticed she commonly lost her train of thought in mid-sentence, and often asked them if they had carried out the tasks that she mistakenly thought she had asked them to do.

— “Reversal of cognitive decline: A novel therapeutic program,” UCLA/Buck Institute, 2014

Since it was first described over 100 years ago, Alzheimer’s disease has been without an effective treatment.

That may finally be about to change: In the first, small study of a novel, personalized and comprehensive program to reverse memory loss, nine of 10 participants, including those described above, displayed subjective or objective improvement in their memories beginning within three to six months.

Six patients had discontinued working or had been struggling at their jobs at the time they joined the study; all were able to return to their jobs or continue working with improved performance, and their improvements have been sustained. (The patient in treatment the longest has been receiving the therapy for two-and-a-half years.)

Among the 10 were patients with memory loss associated with Alzheimer’s disease, amnestic mild cognitive impairment or subjective cognitive impairment (in which the patient reports cognitive problems). One patient who had been diagnosed with late stage Alzheimer’s did not improve.

The study was conducted Dr. Dale Bredesen of the UCLA Mary S. Easton Center for Alzheimer’s Disease Research and the Buck Institute for Research on Aging. It is the first to suggest that memory loss in patients may be reversed — and improvement sustained — using a complex, 36-point therapeutic program that involves comprehensive diet changes, brain stimulation, exercise, sleep optimization, specific pharmaceuticals and vitamins, and multiple additional steps that affect brain chemistry.

The findings are published in the current online edition of the journal Aging.

Bredesen, UCLA’s Augustus Rose Professor of Neurology, director of the Easton Center and the paper’s author, said the findings are “very encouraging,” but he added that the results are anecdotal, and a more extensive, controlled clinical trial is needed.

No single drug has been found to stop or even slow the progression of Alzheimer’s, and drugs have only had modest effects on symptoms. “In the past decade alone, hundreds of clinical trials have been conducted for Alzheimer’s, without success, at an aggregate cost of over $1 billion,” said Bredesen, who also is a professor at the Buck Institute.

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‘Frenemy’ in Parkinson’s takes to crowdsourcing


Protein regulates neuronal communication by self-association.

The protein alpha-synuclein is a well-known player in Parkinson’s disease and other related neurological conditions, such as dementia with Lewy bodies. Its normal functions, however, have long remained unknown. An enticing mystery, say researchers, who contend that understanding the normal is critical in resolving the abnormal.

Alpha-synuclein typically resides at presynaptic terminals – the communication hubs of neurons where neurotransmitters are released to other neurons. In previous studies, Subhojit Roy, M.D., Ph.D., and colleagues at the UC San Diego School of Medicine had reported that alpha-synuclein diminishes neurotransmitter release, suppressing communication among neurons. The findings suggested that alpha-synuclein might be a kind of singular brake, helping to prevent unrestricted firing by neurons. Precisely how, though, was a mystery.

Then Harvard University researchers reported in a recent study that alpha-synuclein self-assembles multiple copies of itself inside neurons, upending an earlier notion that the protein worked alone. And in a new paper, published this month in Current Biology, Roy, a cell biologist and neuropathologist in the departments of pathology and neurosciences, and co-authors put two and two together, explaining how these aggregates of alpha-synuclein, known as multimers, might actually function normally inside neurons.

First, they confirmed that alpha-synuclein multimers do in fact congregate at synapses, where they help cluster synaptic vesicles and restrict their mobility. Synaptic vesicles are essentially tiny packages created by neurons and filled with neurotransmitters to be released. By clustering these vesicles at the synapse, alpha-synuclein fundamentally restricts neurotransmission. The effect is not unlike a traffic light – slowing traffic down by bunching cars at street corners to regulate the overall flow.

“In normal doses, alpha-synuclein is not a mechanism to impair communication, but rather to manage it. However it’s quite possible that in disease, abnormal elevations of alpha-synuclein levels lead to a heightened suppression of neurotransmission and synaptic toxicity,” said Roy.

“Though this is obviously not the only event contributing to overall disease neuropathology, it might be one of the very first triggers, nudging the synapse to a point of no return. As such, it may be a neuronal event of critical therapeutic relevance.”

Indeed, Roy noted that alpha-synuclein has become a major target for potential drug therapies attempting to reduce or modify its levels and activity.

Co-authors include Lina Wang, Utpal Das and Yong Tang, UC San Diego; David Scott, Massachusetts Institute of Technology; and Pamela J. McLean, Mayo Clinic-Jacksonville.

Funding support for this research came from National Institutes of Health (grant P50AG005131-project 2) and the UC San Diego Alzheimer’s Disease Research Center.

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Neural compensation found in people with Alzheimer’s-related protein


Study provides evidence of plasticity in aging brain that appears to be beneficial.

Shown are scans that represent all subjects with beta-amyloid deposits in their brain. The yellow and orange colors show areas where greater brain activation was associated with the formation of more detailed memories. (Image courtesy of Jagust Lab)

The human brain is capable of a neural workaround that compensates for the buildup of beta-amyloid, a destructive protein associated with Alzheimer’s disease, according to a new study led by UC Berkeley researchers.

The findings, published today (Sept. 14) in the journal Nature Neuroscience, could help explain how some older adults with beta-amyloid deposits in their brain retain normal cognitive function while others develop dementia.

“This study provides evidence that there is plasticity or compensation ability in the aging brain that appears to be beneficial, even in the face of beta-amyloid accumulation,” said study principal investigator Dr. William Jagust, a professor with joint appointments at UC Berkeley’s Helen Wills Neuroscience Institute, the School of Public Health and Lawrence Berkeley National Laboratory.

Previous studies have shown a link between increased brain activity and beta-amyloid deposits, but it was unclear whether the activity was tied to better mental performance.

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Aging brain influenced by experiences throughout life


Study from UC Davis and University of Victoria examines demographics and cognitive aging.

Early life experiences, such as childhood socioeconomic status and literacy, may have greater influence on the risk of cognitive impairment late in life than such demographic characteristics as race and ethnicity, a large study by researchers with the UC Davis Alzheimer’s Disease Center and the University of Victoria, Canada, has found.

“Declining cognitive function in older adults is a major personal and public health concern,” said Bruce Reed, professor of neurology and associate director of the UC Davis Alzheimer’s Disease Center.

“But not all people lose cognitive function, and understanding the remarkable variability in cognitive trajectories as people age is of critical importance for prevention, treatment and planning to promote successful cognitive aging and minimize problems associated with cognitive decline.”

The study, “Life Experiences and Demographic Influences on Cognitive Function in Older Adults,” is published online in Neuropsychology, a journal of the American Psychological Association. It is one of the first comprehensive examinations of the multiple influences of varied demographic factors early in life and their relationship to cognitive aging.

The research was conducted in a group of over 300 diverse men and women who spoke either English or Spanish. They were recruited from senior citizen social, recreational and residential centers, as well as churches and health-care settings. At the time of recruitment, all study participants were 60 or older, and had no major psychiatric illnesses or life threatening medical illnesses. Participants were Caucasian, African-American or Hispanic.

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$10M grant to bring online respite to dementia caregivers


UCSF, UNMC to offer education, support and care.

Katherine Possin, UC San Francisco

UC San Francisco and the University of Nebraska Medical Center have been awarded a $10 million grant from the Centers for Medicare & Medicaid Innovation to create a new Web-based model of dementia care. It will provide around-the-clock consultations for patients and their families, online education and, for a subset of patients, remote monitoring with smart phones and home sensors.

The Dementia Care Ecosystem will not replace clinicians, but rather bring educational resources developed over the last decade by the UCSF Memory and Aging Center (MAC) to patients and their families, while enabling clinicians to monitor their patients from afar.

“Our hope is this is going to radically improve the way dementia patients are cared for,” said Katherine Possin, Ph.D., who is an assistant professor of neuropsychology at UCSF. “We hope we’ll show this works, and that it can be adopted nationwide.”

Each patient will have a navigator, who will check in by telephone or with a personal visit, as well as by monitoring communication with patients and their families through an Internet dashboard, created with the help of Salesforce. Navigators will be people without a formal medical degree and will be supervised closely by nurses, social workers and pharmacists with expertise in dementia care.

These navigators will triage calls, making sure that patients see nurses and doctors when necessary and helping with other things that don’t require medical expertise, such as a hazardous situation in the home that could cause the patient to fall. Meanwhile, patients and their families will be able to get training online to help make financial plans and work through tough medical decisions before their loved ones have reached a crisis stage.

Researchers hope to create a virtual care system that is supportive enough to protect the mental and physical health of caregivers, who tend to neglect their own needs. If caregivers learn to cope better, patients may be able to remain at home longer before moving into assisted living. Last year, according to the Alzheimer’s Association, about 15.5 million people in the United States were caring for friends and family members with dementia. Nearly 60 percent said the work was highly stressful and more than a third reported symptoms of depression.

Bruce Miller, UC San Francisco

“Our ecosystem will have wisdom and experience continuously piped in every day to caregivers who are overwhelmed,” said Bruce Miller, M.D., director of the MAC, who holds the A.W. and Mary Margaret Clausen Distinguished Professorship in Neurology at UCSF. “Typically, these people have a hard time getting through to anyone in the medical system.”

Some patients in the study will have an added level of technology-based care. They will use smart phones and electronic wristbands to record their activity levels, count the number of steps they take and measure how far they range from home. And a small number will have sensors placed inside their homes to detect behavior changes that could signal the onset of a health problem, like being up all night, staying in bed all day or going to the bathroom more times than usual.

“If someone, instead of getting up two times a night, is getting up four or five times a night, we might send a nurse the next morning to their home to get a urine sample, and if it’s bad start the patient on antibiotics,” said Steve Bonasera, M.D., Ph.D., an associate professor of geriatrics at UNMC, who did his fellowship at UCSF. “We’re going to be monitoring people who are a seven- or eight-hour drive from my office in Omaha.”

The system will also monitor the drugs that patients take and flag high risk and inappropriate medications, such as antipsychotics and benzodiazepines that can send patients with certain forms of dementia to the emergency room. It will also flag medications that should not be combined.

Initial projections are that the improved caregiver support, more continuous access to medical help and medication management will reduce emergency room visits by a half, cut hospitalizations by almost a third and delay the move into a nursing home for six months. This is projected to save $4.3 million over the three years of the grant.

The MAC already has a well developed website that attracts traffic from around the world. Some of the center’s recorded lectures on caring for people with dementia have been viewed hundreds of thousands of times. Researchers said that once families have easy access to educational resources, office visits will become less pressured and patients and their families will be able to take more time to absorb information and make important decisions.

“The idea of 24/7 telephone access to clinicians with expertise in dementia has really resonated with caregivers,” said Jennifer Merrilees, R.N., Ph.D., a clinical nurse specialist at the MAC who will oversee the care that is dispensed online. “That’s what’s really made their faces light up when I’ve described it to them.”

Beginning this fall, 2,100 patients, all diagnosed with varying stages of dementia, will be enrolled through San Francisco General Hospital and Trauma Center, UCSF Medical Center and the UCSF MAC clinics and Chinatown Clinics, as well as UNMC and other service organizations in Nebraska serving the elderly.

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A cure for Alzheimer’s requires a parallel team effort


UC expert simulates benefits of a hypothetical megafund devoted to Alzheimer’s therapeutics.

Kenneth Kosik, UC Santa Barbara

For the more than 5 million Americans and 35 million people worldwide suffering from Alzheimer’s disease, the rate of progress in developing effective therapeutics has been unacceptably slow.

To address this urgent need, UC Santa Barbara’s Kenneth S. Kosik and colleagues are calling for a parallel drug development effort in which multiple mechanisms for treating Alzheimer’s are investigated simultaneously rather than the current one-at-a-time approach. In an article published today (June 18) in Science Translational Medicine, the research team — Kosik; Andrew W. Lo and Jayna Cummings of the MIT Sloan School of Management’s Laboratory for Financial Engineering and Carole Ho of Genentech Inc. — presents a simulation of a hypothetical megafund devoted to bringing Alzheimer’s disease therapeutics to fruition.

According to Kosik, the Harriman Professor of Neuroscience Research and co-director of the Neuroscience Research Institute at UCSB, a “multiple-shots-on-goal” approach not only accelerates the search for a cure but also increases the probability of at least one or two successes within the next decade, thereby reducing the financial risk to investors. “But more basic research is needed to increase the probability of success, decrease the correlation among projects and make available more potential targets,” he added.

Unlike cancer and heart disease, which have many therapeutic targets — proteins and nucleic acids to which drugs are directed — the basic science of Alzheimer’s disease biology is still in its early days. What’s more, not enough Alzheimer’s disease targets exist to mitigate risk and thereby attract private-sector investment. But given how much the U.S. government is already paying each year for Alzheimer’s disease-related treatments through Medicare and Medicaid — more than $150 billion in 2013 — a government-supported public-private partnership may yield an excellent return on investment from the taxpayer’s perspective.

Using generic information on the drug development process and qualitative judgments by two of the co-authors (Kosik and Ho) who are experts in neurodegenerative diseases and translational medicine, the simulation shows that a hypothetical portfolio of 64 distinct Alzheimer’s disease drug development programs costing $38.4 billion would yield an expected financial return of -14.3 percent and a 13 percent probability that no project will reach approval. This level of risk implies that large-scale private-sector funding is unlikely to be directed to such an effort.

The analysis may help to explain why no new drugs for treating Alzheimer’s disease have been approved by the U.S. Food and Drug Administration since 2003. Currently only four drugs are on the market, and all four treat only the symptoms of Alzheimer’s disease without altering its course. However, when measured against the potential cost savings to the U.S. taxpayer over a 20-year horizon, therapeutics that delay the onset of Alzheimer’s disease or limit the progression of the disease can generate the equivalent of double-digit investment returns from the taxpayer’s perspective.

To quantify these potential cost savings, the authors used projections developed by the Alzheimer’s Association and found that savings could range from $813 billion to $1.5 trillion over a 30-year period, more than offsetting the cost of a $38 billion megafund. Domestically, the cost of treating Alzheimer’s disease is approximately $200 billion per year, of which an estimated 70 percent is covered by Medicare and Medicaid. Total related costs worldwide are already estimated to be about 1 percent of global gross domestic product.

Given that Alzheimer’s disease has the potential to bankrupt medical systems — the Alzheimer’s Association projects that the costs of care could soar to $1 trillion in the U.S. by 2050 — governments around the world have a strong incentive to invest more heavily in the development of Alzheimer’s disease therapeutics and catalyze greater private-sector participation.

“Unless government funding for basic research in the molecular biology of neurodegenerative diseases increases dramatically in the near future,” Kosik said, “it seems unlikely that the private sector will be able to produce effective Alzheimer’s disease therapies over the next few decades.”

Although the implications of the simulation seem clear, the authors acknowledge the need for much more research to calibrate the parameters of their analysis as well as to develop a more comprehensive set of potential Alzheimer’s disease targets with which to compute investment returns.

“My colleagues and I hope that this simulation will be the starting point for a more active collaboration among all stakeholders to explore the potential of a public-private partnership focused on Alzheimer’s disease therapeutics,” Kosik concluded.

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How our brains store recent memories, cell by single cell


Findings may shed light on how to treat neurological conditions like Alzheimer’s, epilepsy.

Human neuron showing actin formation in response to stimulation. (Image by Michael A. Colicos, UC San Diego)

Confirming what neurocomputational theorists have long suspected, researchers at the Dignity Health Barrow Neurological Institute in Phoenix and UC San Diego report that the human brain locks down episodic memories in the hippocampus, committing each recollection to a distinct, distributed fraction of individual cells.

The findings, published in today’s (June 16) early edition of PNAS, further illuminate the neural basis of human memory and may, ultimately, shed light on new treatments for diseases and conditions that adversely affect it, such as Alzheimer’s disease and epilepsy.

“To really understand how the brain represents memory, we must understand how memory is represented by the fundamental computational units of the brain – single neurons – and their networks,” said Peter N. Steinmetz, M.D., Ph.D., program director of neuroengineering at Barrow and senior author of the study. “Knowing the mechanism of memory storage and retrieval is a critical step in understanding how to better treat the dementing illnesses affecting our growing elderly population.”

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