TAG: "Alzheimer’s"

New dean is biological sciences booster


Frank LaFerla, renowned for his Alzheimer’s work, hopes to raise UC Irvine school’s profile.

Frank LaFerla, UC Irvine

For a scientist widely considered an international leader in Alzheimer’s disease research, Frank LaFerla joined the UC Irvine faculty in 1995, interestingly enough, without ever having taken a single neuroscience class.

LaFerla had received a doctorate in virology and was studying AIDS-related dementia when he sat in on his first neurobiology course, one taught by James McGaugh and Norman Weinberger, two of the nation’s top learning and memory researchers. The lessons obviously made a great impression on the young scientist.

Since that time, LaFerla has made key research breakthroughs that show promise for treating Alzheimer’s and other neurodegenerative diseases. He has served in numerous leadership roles, including as chair of the Department of Neurobiology & Memory and director of the campus’s Institute for Memory Impairments and Neurological Disorders (UCI MIND), a research center internationally acclaimed for its work on disorders of the brain, particularly those that are age-related.

Last December, LaFerla became the Hana & Francisco J. Ayala Dean of the newly renamed Francisco J. Ayala School of Biological Sciences, heading the third-largest school on campus, with nearly 4,000 students majoring in one of its four undergraduate degree programs.

“Frank brings enormous enthusiasm and optimism to everything he does,” says McGaugh, a research professor of neurobiology & behavior and former biological sciences dean. “He wants to take actions that emphasize the character and the contributions of the school to the campus and to the public. It’s hard to imagine a more qualified person for the position.”

And with UC Irvine approaching its golden anniversary, LaFerla says, he aims to “take the school to the next level.”

He assumes the helm at a time when the biological sciences are critical to addressing such global concerns as sustainable food production, ecosystem restoration, optimized biofuel manufacturing and improved human health. And he wants to ensure that UC Irvine plays a part.

“Our brand is ‘Understanding Life: Transforming Our World,’” LaFerla says. “We will be excellent ambassadors of science who are trying to solve very important issues.”

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New therapeutic target discovered for Alzheimer’s disease


Drug candidate blocks production of disease-causing neurotoxins in mouse models.

Vivian Hook, UC San Diego

A team of scientists from the UC San Diego School of Medicine, the Medical University of South Carolina and San Diego-based American Life Science Pharmaceuticals Inc., report that cathepsin B gene knockout or its reduction by an enzyme inhibitor blocks creation of key neurotoxic pGlu-Aβ peptides linked to Alzheimer’s disease (AD). Moreover, the candidate inhibitor drug has been shown to be safe in humans.

The findings, based on AD mouse models and published online in the Journal of Alzheimer’s Disease, support continued development of cysteine protease inhibitors as a new drug target class for AD. “No other therapeutic program is investigating cysteine protease inhibitors for treating AD,” said collaborator Vivian Hook, Ph.D., professor in the UC San Diego Skaggs School of Pharmacy and Pharmaceutical Sciences and in the UC San Diego School of Medicine.

Current AD drugs treat some symptoms of the devastating neurological disorder, but none actually slow its progress, prevent or cure it. No new AD drug has been approved in more than a decade.

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Blood test IDs those at risk for Alzheimer’s


UC Irvine researchers among authors of study.

Claudia Kawas, UC Irvine

Researchers – including those at UC Irvine – have discovered and validated a blood test that can predict with greater than 90 percent accuracy whether a healthy person will develop mild cognitive impairment or Alzheimer’s disease within three years.

Described in the April issue of Nature Medicine, the study heralds the potential for developing treatment strategies for Alzheimer’s at an earlier stage, when therapy would be more effective at slowing or preventing symptoms.

It’s the first known published report of blood-based biomarkers for preclinical Alzheimer’s. The test identifies 10 lipids, or fats, in the blood that predict disease onset. It could be ready for use in clinical studies in as few as two years, and researchers say that other diagnostic uses are possible.

Dr. Claudia Kawas, the Nichols Chair in Neuroscience at UC Irvine, is among the authors of the study, which was led by Dr. Howard Federoff of Georgetown University. It involved 525 healthy participants aged 70 and older who gave blood samples upon enrolling and at various points in the study. More than 100 of them came from UC Irvine’s Orange County Aging Study.

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Researchers hone in on Alzheimer’s disease


Gordon supercomputer helps guide new drug designs.

Researchers studying peptides using the Gordon supercomputer at the San Diego Supercomputer Center (SDSC) at UC San Diego have found new ways to elucidate the creation of the toxic oligomers associated with Alzheimer’s disease.

Igor Tsigelny, a research scientist with SDSC, the UCSD Moores Cancer Center and the Department of Neurosciences, focused on the small peptide called amyloid-beta, which pairs up with itself to form dimers and oligomers.

The scientists surveyed all the possible ways to look at the dynamics of conformational changes of these peptides and the possibility that they might organize into the oligomers theorized to be responsible for the degenerative brain disease. In the Feb. 14 issue of the Journal of Alzheimer’s Disease, the researchers suggest their results may generate new targets for drug development.

“Our research has identified amino acids for point mutations that either enhanced or suppressed the formation and toxicity of oligomer rings,” said Tsigelny, the study’s lead author. “Aggregation of misfolded neuronal proteins and peptides may play a primary role in neurodegenerative disorders, including Alzheimer’s disease.”

Tsigelny also noted that recent improvements in computational processing speed have allowed him and other researchers to use a variety of tools, including computer simulations, to take new approaches to examining amyloid-beta, which has proven too unstable for traditional approaches such as X-ray crystallography.

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High good, low bad cholesterol levels are healthy for the brain, too


Study suggests potential new approach to lowering prevalence of Alzheimer’s disease.

Bruce Reed, UC Davis

Bruce Reed, UC Davis

High levels of “good” cholesterol and low levels of “bad” cholesterol are correlated with lower levels of the amyloid plaque deposition in the brain that is a hallmark of Alzheimer’s disease, in a pattern that mirrors the relationship between good and bad cholesterol in cardiovascular disease, UC Davis researchers have found.

“Our study shows that both higher levels of HDL — good — and lower levels of LDL — bad — cholesterol in the bloodstream are associated with lower levels of amyloid plaque deposits in the brain,” said Bruce Reed, lead study author and associate director of the UC Davis Alzheimer’s Disease Center.

“Unhealthy patterns of cholesterol could be directly causing the higher levels of amyloid known to contribute to Alzheimer’s, in the same way that such patterns promote heart disease,” he said.

The relationship between elevated cholesterol and increased risk of Alzheimer’s disease has been known for some time, but the current study is the first to specifically link cholesterol to amyloid deposits in living human study participants, Reed said.

The study, “Associations Between Serum Cholesterol Levels and Cerebral Amyloidosis,” is published online today (Dec. 30) in JAMA Neurology.

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UC Irvine names new dean of biological sciences


Noted Alzheimer’s researcher Frank LaFerla will take school’s reins Jan. 1.

Frank LaFerla, UC Irvine

Frank LaFerla, UC Irvine

UC Irvine Chancellor Michael V. Drake announced today (Dec. 23) that Frank M. LaFerla has been appointed the Hana & Francisco J. Ayala Dean of the School of Biological Sciences, effective Jan. 1, 2014.

LaFerla, Chancellor’s Professor and chair of the Department of Neurobiology & Behavior since 2011, joined UC Irvine in 1995 as an assistant professor in the then-named Department of Psychobiology. Since that time, he has served in numerous leadership roles, including as associate director and now director of the Institute for Memory Impairments and Neurological Disorders (UCI MIND), a research center internationally acclaimed for its work on brain disorders, particularly those that are age-related.

He was also founding director of the Interdepartmental Neuroscience Program, which united several departments and faculty concerned with neuroscience under one major programmatic initiative and has since facilitated the recruitment to UC Irvine of numerous outstanding graduate students.

LaFerla, who holds a doctorate from the University of Minnesota and a bachelor’s degree from St. Joseph’s University in Philadelphia, has several research interests, including the molecular biology of Alzheimer’s disease and other neurodegenerative disorders, presenilins and calcium signaling, learning and memory, and transgenic and genetically modified animal models. He was the first to engineer mice that develop the cerebral plaques and tangles that characterize Alzheimer’s, providing researchers with a crucial “living laboratory” of the disease. LaFerla’s mice have made a huge impact on his work and on Alzheimer’s research around the world.

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UC San Diego launches unprecedented Down syndrome study


Goal: gain better understanding of adults with the disease, discover indicators of Alzheimer’s.

William Mobley, UC San Diego

William Mobley, UC San Diego

To many, Down syndrome (DS) is a childhood condition. But improved health care means that individuals with DS now routinely reach age 50 or 60 years of age, sometimes beyond.  However, if they live long enough, people with Down syndrome are almost certain to develop Alzheimer’s disease (AD).

Risk estimates vary, but the National Down Syndrome Society says that nearly 25 percent of individuals with DS over the age of 35 show signs of Alzheimer’s-type dementia, a percentage that dramatically increases with age. Almost all develop dementia by the age of 60.

“The more we learn about Down syndrome and Alzheimer’s disease, the more we realize these conditions – one seen at birth, the other quite late in life – are two sides of the same coin,” said William C. Mobley, M.D., Ph.D., professor and chair of the Department of Neurosciences at UC San Diego School of Medicine. “Autopsies of DS and AD brains reveal virtually identical pathologies – the same telltale amyloid plaques and neurofibrillary tangles.”

Under the auspices of the Alzheimer’s Disease Cooperative Study (ADCS), based at the UC San Diego School of Medicine, a new clinical study called the Down Syndrome Biomarker Initiative (DSBI) was launched in March. According to the study’s director, Michael Rafii, M.D., Ph.D. – medical director of the ADCS – its aim is to discover indicators of Alzheimer’s and study progression of the disease, with the ultimate goal of better understanding brain aging and AD in adults with Down syndrome.

The three-year pilot study has enrolled 12 participants, aged 30 to 60 years of age. Study participants will be screened for various biomarkers of AD, using tests that include three types of brain scans, retinal amyloid imaging and blood tests, among others.

“Findings to date using MRI and amyloid PET scans indicate that individuals with Down syndrome show the same brain patterns as those in the general population with the earliest stages of the memory-robbing disease, called prodromal AD,” said Rafii. He added that indications of increased brain amyloid deposition – the insoluble protein aggregates found in the brains of patients with AD that are thought to be an underlying cause of the disease – is similar in individuals with DS and those in the general population with AD.

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Wellcome Trust awards funds to combat Alzheimer’s disease


Gladstone founding President Robert Mahley and his team to fast-track drug discovery.

Robert Mahley

Robert Mahley

Alzheimer’s disease is one of the greatest challenges facing modern medicine, but there is new hope in the fight against this deadly disease. Today, renowned Alzheimer’s researcher and founding president of the Gladstone Institutes, Robert Mahley, M.D., Ph.D., has received a Seeding Drug Discovery Award from the Wellcome Trust.

Mahley, along with Gladstone investigator Yadong Huang, M.D., Ph.D., will use the funding to identify new chemical compounds that can target apolipoprotein E4 (apoE4) — the strongest genetic risk factor for developing Alzheimer’s. Specifically, the funding will enable Gladstone researchers to collaborate with Numerate, a South San Francisco-based chemoinformatics company, to develop small-molecule therapies that prevent the damaging effects of apoE4 on the brain.

“We are truly honored and humbled to be recognized by the Wellcome Trust,” said Mahley, who is also a professor of medicine at UC San Francisco, with which Gladstone is affiliated. “Decades of research have identified the strong connection between apoE4 and Alzheimer’s. Now, with support from the trust and with our industry partner Numerate, we can move forward with finding ways to neutralize this toxic protein, thus halting the disease’s devastating effects.”

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Grant supports creation of patient-derived stem cell lines to study Alzheimer’s


UC Irvine MIND effort is part of institute’s larger iPS Cell Bank Initiative.

Frank LaFerla (left) and Mathew Blurton-Jones of UC Irvine will use a special type of stem cell to explore the underlying biology and treatment of Alzheimer's disease.

Frank LaFerla (left) and Mathew Blurton-Jones of UC Irvine will use a special type of stem cell to explore the underlying biology and treatment of Alzheimer's disease.

Researchers at UC Irvine’s Institute for Memory Impairments and Neurological Disorders have received a two-year, $600,000 grant from the National Institute on Aging to develop and study patient-derived stem cell lines.

Led by Frank LaFerla and Mathew Blurton-Jones, the UCI MIND team will create as many as 40 sets of induced pluripotent stem cells to explore the underlying biology of Alzheimer’s disease and test novel therapeutic approaches.

Few discoveries have as much potential to transform modern medical research as iPS cells. They’re capable of giving rise to every cell type in the human body, including the key cell types implicated in Alzheimer’s disease: neurons, astrocytes and microglia.

Because iPS cells can be generated from patients with a given disease, they offer a powerful new way to study the influence of genetics on disease risk and progression. UCI MIND investigators, who do not use embryonic stem cells, have pioneered this avenue of research specifically for Alzheimer’s disease.

“The ability to reprogram cells from adult subjects to make iPS cells is a giant leap forward for science,” said LaFerla, UCI MIND director and Chancellor’s Professor and chair of neurobiology & behavior. “And we’re excited that UCI MIND is at the forefront of using this technology in the battle against Alzheimer’s disease.”

It’s notable that iPS cells can be derived from skin or blood samples. Anyone, even older adults, can easily donate the material needed. Additionally, by harvesting these cells from the patient, transplantation-based therapies could – researchers hope – one day be administered without the need for immunosuppression.

The work funded by the NIA falls under the UCI MIND iPS Cell Bank Initiative, an effort to create a repository of Alzheimer’s disease iPS cells that can be accessed by scientists around the world.

The iPS Cell Bank, which will be part of UCI MIND’s National Institutes of Health-designated Alzheimer’s Disease Research Center, is receiving considerable support through the Keith Swayne Family Challenge.

In honor of his wife, Judy Swayne, who has Alzheimer’s disease, Keith Swayne and his family have pledged $150,000 in the form of a challenge. They will match every dollar raised up to $150,000, bringing the total to $300,000 when the challenge is met. These funds will help establish and expand the UCI MIND iPS Cell Bank.

For more information about the Keith Swayne Family Challenge, go to http://mind.uci.edu/keith-swayne-family-challenge.

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Origin of Alzheimer’s gene discovered


UC Santa Barbara researcher tracks source to a single founder dating from Habsburg Spain.

Kenneth Kosik, UC Santa Barbara

Kenneth Kosik, UC Santa Barbara

The age and origin of the E280A gene mutation responsible for early-onset Alzheimer’s in a Colombian family with an unusually high incidence of the disease has been traced to a single founder dating from the 16th century.

Kenneth S. Kosik, Harriman Professor in Neuroscience at UC Santa Barbara and co-director of the campus’s Neuroscience Research Institute (NRI), conducted the study. The findings appear in the journal Alzheimer’s & Dementia.

“Some mutations just increase your risk, but this mutation is not a risk,” Kosik said. “This mutation is highly penetrant, which means that if you carry the mutation, you will get early-onset Alzheimer’s disease.”

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Understanding a protein’s role in familial Alzheimer’s disease


Findings could inform development of effective drugs for the neurodegenerative disease.

Lawrence Goldstein, UC San Diego

Lawrence Goldstein, UC San Diego

Researchers at the UC San Diego School of Medicine have used genetic engineering of human induced pluripotent stem cells to specifically and precisely parse the roles of a key mutated protein in causing familial Alzheimer’s disease (AD), discovering that simple loss-of-function does not contribute to the inherited form of the neurodegenerative disorder.

The findings, published online in the journal Cell Reports, could help elucidate the still-mysterious mechanisms of Alzheimer’s disease and better inform development of effective drugs, said principal investigator Lawrence Goldstein, Ph.D., professor in the Departments of Cellular and Molecular Medicine and Neurosciences and director of the UC San Diego Stem Cell Program.

“In some ways, this is a powerful technical demonstration of the promise of stem cells and genomics research in better understanding and ultimately treating AD,” said Goldstein, who is also director of the new Sanford Stem Cell Clinical Center at UC San Diego. “We were able to identify and assign precise limits on how a mutation works in familial AD. That’s an important step in advancing the science, in finding drugs and treatments that can slow, maybe reverse, the disease’s devastating effects.”

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Gladstone scientist to receive Pacesetter Award


Lennart Mucke honored for leadership in Alzheimer’s disease research.

Lennart Mucke

Lennart Mucke

Lennart Mucke, M.D., who directs neurological research at the Gladstone Institutes, next week will receive the ARCS Foundation’s 2013 Pacesetter Award for his lifelong dedication to overcoming Alzheimer’s disease — and for mentoring students to take a similar approach.

The award, the second received by a Gladstone scientist, underscores the quality of research being conducted at this independent biomedical-research organization that was founded in San Francisco in 1979. The ARCS Foundation — which provides awards to academically outstanding U.S. citizens studying science, engineering and medical research — will present the award to Mucke at an Oct. 28 luncheon honoring and celebrating ARCS Foundation scholars. Mucke will give the luncheon’s keynote address, speaking about what it will take to defeat Alzheimer’s disease.

“Dr. Mucke leads Gladstone’s neurological research with a strong emphasis on collaboration and multi-pronged approaches to finding new disease solutions,” said Roulhac Austin, ARCS Foundation Northern California Chapter co-president. “The ARCS membership applauds this approach and believes it has contributed to Dr. Mucke’s major insights into Alzheimer’s disease — insights we hope will lead to new and desperately needed treatments.”

To be sure, this acknowledgement of Mucke’s success in Alzheimer’s research comes at a critical time. Currently, there are no effective treatments to slow, prevent or halt this neurodegenerative disease — which robs people of critical brain functions including the ability to retain memories. As our nation’s sixth leading cause of death, Alzheimer’s afflicts one in nine Americans aged 65 or older, according to the Alzheimer’s Association. And the number of those with Alzheimer’s is expected to nearly triple by 2050 — threatening to overwhelm our health care system.

In accepting the Pacesetter Award, Mucke joins the ranks of other pre-eminent San Francisco Bay Area executives who ARCS also has honored, including John Chambers, chairman and CEO of Cisco Systems; Paul Otellini, former president and CEO of Intel; and Susan Desmond-Hellmann, chancellor of  UC San Francisco, with which Gladstone is affiliated.

“I am deeply honored to receive this award from an organization whose objectives are so nicely aligned with Gladstone’s,” said Mucke, who is also a professor of neurology and the Joseph B. Martin Distinguished Professor of Neuroscience at UCSF. “They promote science and medical research — and emphasize the values of using a collaborative, multifaceted approach. These are founding tenets at Gladstone and will be critical to achieving our goals of better treating, preventing and ultimately curing neurological diseases such as Alzheimer’s.”

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