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Responding to an article written in AlzForum on the future of Alzheimer's treatment and research from October 7th, Joshua Grill, PhD, from UCI MIND, and his colleague, Jason Karlawish, MD, from the University of Pennsylvania, write: Josh Grill, Professor, Psychiatry & Human Behaviorphoto: Steve Zylius/UCI "Anticipation that FDA will grant full approval of lecanemab (or another disease-modifying treatment) invites an exciting but challenging thought exercise: How will such treatments change research and practice for Alzheimer’s disease (AD)? We’ve considered some of the issues. Our top line point is that a new disease-slowing treatment is unlikely to make use of placebo…

UC Irvine, a longtime hub of Alzheimer’s investigation, has been awarded a $47 million grant from the National Institute on Aging to support a team developing next-generation mouse models for studying late-onset Alzheimer’s. … “It’s an incredibly exciting time, and there’s a lot of promise,” said Joshua Grill, director of UCI’s Institute for Memory Impairments and Neurological Disorders. … The project’s next phase will be co-directed by Frank LaFerla, dean of the School of Biological Sciences; Andrea Tenner, a Distinguished Professor of molecular biology and biochemistry; and Kim Green, a professor of neurobiology and behavior. To learn more, click here >

Scientists will develop mouse models to help unravel most common form of disease The UCI research team is directed by (seated, from left) Frank LaFerla, Andrea Tenner and Kim Green. Other investigators include (standing, from left) Marcelo Wood, Arthur Lander, Grant MacGregor, Ian Smith, Vivek Swarup, Craig Stark, Andre Obenaus and Ali Mortazavi. UCI School of Biological Sciences What began with a $70,000 philanthropic gift 12 years ago has grown into the recipient of a $47 million National Institute on Aging grant for Alzheimer’s disease research at the University of California, Irvine. The funds will be parceled out over five…

Campus to receive $10 million over five years for role in Cell Atlas Network UCI research team members will manage brain sample acquisition, processing and characterization as part of the BRAIN Initiative Cell Atlas Network project. They are (from left) Ed Monuki, Elizabeth Head, William Yong, Xiangmin Xu, Craig Stark, Hannah Lui Park and Robert Edwards, along with Mari Perez-Rosendahl (not pictured). Steve Zylius / UCI The University of California, Irvine will participate in a five-year, multi-institutional, $126 million grant from the National Institutes of Health supporting the BRAIN Initiative Cell Atlas Network. The project aims to describe the cells…

UCI MIND's podcast, Spotlight on Care: Alzheimer's Caregiving, was featured in a list of the top Alzheimer's podcasts by Feedspot. The best Alzheimer podcast list is curated from thousands of podcasts on the web and ranked by traffic, social media followers, domain authority & freshness. Watch our latest episodes at spotlightoncare.com. 9. Spotlight on Care: Alzheimer's Caregiving  Irvine, California, US Welcome to Spotlight on Care, the podcast where we share stories, experiences, tips, and advice on caring for loved ones affected by Alzheimer's and other dementias. Spotlight on Care is produced by the University of California, Irvine Institute for Memory Impairments…

Illustration of SHQ. (a) Wayfinding level 6, where locations of three numbered checkpoints are first shown on a map. After the map disappears, participants have to navigate the boat to the numbered checkpoints in order, (b) Flare level 9, where participants navigate the boat from a starting location along the river, until they find a flare gun. Once found, the boat rotates by 180° clockwise and the participants are asked to shoot the gun in the direction of the starting location. Vaisakh Puthusseryppady, a post-doctoral scholar at the University of California, Irvine in the Department of Neurobiology and Behavior writes:…

Early life adversities can have a lifelong impact. Tallie Z. Baram, distinguished professor in the Departments of Anatomy & Neurobiology, Pediatrics, Neurology, and Physiology & Biophysics at the University of California, Irvine, determines why. Listen here > Prof. Tallie Z. Baram Prof. Tallie Z. Baram is the Danette Shepard Professor of Neurological Sciences, with appointments in several departments at UCI. Baram is a developmental neuroscientist and child neurologist and has focused her efforts on the influence of early-life experiences on the developing brain, and on the underlying mechanisms. She is studying this broad topic in two contexts: a) How early-life…

Findings show bone marrow transplantation may be a novel treatment approach July 12, 2022 Albert LaSpada, MD, PhD, distinguished professor of pathology, neurology and biological chemistry in the UCI School of Medicine, is one of the first researchers to examine whether some forms of ALS could be linked to the body's adaptive immune system, which builds up protection as it is exposed to foreign pathogens. Orange, Calif. — The immune system, along with the body's central nervous system, may play a fundamental role in amyotrophic lateral sclerosis (ALS), suggesting that bone marrow transplants may be an effective new treatment for the…

Leslie Thompson discusses how UCI’s collaborative approach can help usher in the next great advancement in healthcare July 11, 2022 “I’ve been involved in many very meaningful research projects in my career, but to be perfectly honest, this is huge for me, as I feel it ultimately can help the families that I so passionately care about,” says Leslie Thompson. Steve Zylius / UCI In February, UCI launched the Institute for Precision Health, a campus-wide, interdisciplinary endeavor that merges UCI’s powerhouse health sciences, engineering, machine learning, artificial intelligence, clinical genomics and data science capabilities. The objective is to identify, create…

Multisite team included UCI, University of Wisconsin–Madison, Wake Forest University July 13, 2022 “Our findings indicate that age-related increases in brain inflammation have a downstream effect on Alzheimer’s disease-related tau proteins and neuronal synaptic integrity,” says Bryce Mander, Ph.D., UCI assistant professor of psychiatry & human behavior and the study’s lead and co-corresponding author. “This results in deficits in the brain’s capacity to generate fast sleep spindles, which contribute to age-related memory impairment in older adults.” UCI School of Medicine Irvine, Calif., July 13, 2022 – A multisite research team from the University of California, Irvine, the University of Wisconsin–Madison and…

Contributed by Mark Mapstone, PhD UCI MIND faculty Mark Mapstone, PhD and Ira Lott, MD collaborated on research that was recently published in JAMA Neurology. Learn more about their findings: Studying Alzheimer’s disease in people with Down syndrome is a very important avenue for research because nearly all people with Down syndrome will develop the brain changes of Alzheimer’s disease. These changes include the abnormal accumulation of two proteins; amyloid and tau. In this study, we wanted to know if we could measure these changes in blood and if these changes accurately reflect the changes happening in the brain.  We…

DOTHAN, Ala. (WTVY) - Alzheimer’s and Dementia affect millions of people worldwide. Changes in the brains of people with the disease can start decades before the person actually experiences symptoms, that’s according to the AHEAD Study. With June being Alzheimer’s and Brain Awareness month, doctors and researchers of the AHEAD study are urging people to be conscious about their health and their loved ones. Doctor Josh Grill, a University of California Irvine professor, shares tips to improve and become mindful of your brain health. He said taking part in physical exercise, eating a healthy diet, getting a good night’s sleep…

Image Credit: David Tett via Centre for Ageing Better Exercise could be a powerful defense against Alzheimer’s disease. Three dementia researchers explain how it works. NOVA - When it comes to dementia prevention, sleep and exercise may work together, says neuroscientist Miranda Chappel-Farley, a Ph.D. candidate at University of California, Irvine. … Together, they create a powerful bulwark against dementia and represent a lifestyle factor ignored at your peril, says Chappel-Farley, who cautions against “targeting exercise but not paying attention to sleep.” Read more here >

Contributed by David Sultzer, MD and Joshua Grill, PhD An FDA Advisory Committee met on June 17 to provide input to the Agency regarding the effectiveness of pimavanserin for the treatment of psychosis in Alzheimer’s disease.  The Committee voted 9 to 3, with the majority finding insufficient evidence of effectiveness in this population. This input comes on the heels of an FDA review last year that declined to approve pimavanserin for psychosis in a broad group of dementia syndromes, including Alzheimer’s disease, vascular dementia, Lewy body and Parkinson’s disease dementia, and frontotemporal dementias.  At that time, the Agency felt that…

The multidisciplinary team will focus on participant recruitment and retainment for Alzheimer’s disease and related disorders research Josh Grill, left, and Daniel Gillen will examine what role recruitment registries for ADRD research can play in overcoming exclusions to improve research outcomes. What is the best way to recruit participants to join a clinical studies registry, and can such registries help better diversify clinical research samples? These are two critical questions that UCI researchers are tackling with a new National Institutes of Health grant, “Recruiting and Retaining Participants from Disadvantaged Neighborhoods in Registries.” The work will be led by Joshua Grill, professor…

Findings will advance development of better early diagnostic tools, new treatment strategies “This project will capture a composite of disease features to expand our understanding of the brain circuits susceptible to aging and Alzheimer’s. Our findings will facilitate the development of more effective early diagnostic tools and the discovery of new therapies,” says UCI’s Xiangmin Xu. Steve Zylius / UCI The University of California, Irvine has been awarded a five-year, $14 million grant from the National Institutes of Health to study brain circuits that are susceptible to aging and Alzheimer’s disease. The research findings will advance the development of early…

In a blunt rejection of current norms, two leaders of biomarker disclosure research argue research participants should have the opportunity to know whether they have biomarkers of Alzheimer’s disease . Biomarkers, or biological indicators of a disease, are essential to the study and diagnosis of Alzheimer’s and other diseases that cause dementia. Clinicians use imaging such as MRI and PET scans to measure biomarkers and make accurate diagnoses. Blood tests are fast becoming available too. The tests also allow researchers to develop targeted drug therapies. But in both clinical care and research, biomarker results are infrequently disclosed. Insurers typically do…

Hope Dies Last - Alzheimer's: A Journey of Lost Memories, comes out TODAY at 3:30pm! Check out this clip of UCI MIND Director, Joshua Grill, Ph.D. discussing the impacts of Alzheimer's disease on Orange County residents. Tune in today at 3:30pm on KDOCTV for the full program!

After decades of research into the causes and treatment of Parkinson's disease, UCI Health neurologist Dr. Claire Henchcliffe is hopeful that a new cell therapy can finally bring meaningful relief to patients with the progressive neurodegenerative movement disorder. A national expert on Parkinson's disease, she is one of a small group of U.S. researchers conducting a first-in-human clinical trial of transplanted stem cells engineered to replace dopamine-producing neurons that are destroyed by the debilitating and incurable condition. As the brain loses its ability to produce the potent neurotransmitting chemical, that leads to the tremors, stiffness, slowness and lack of coordination seen in Parkinson's patients. The…

The Collaborative Approach for Asian Americans and Pacific Islanders Research and Education (CARE): A recruitment registry for Alzheimer's disease and related dementias, aging, and caregiver-related research

Blood pressure variability is an emerging risk factor for cognitive decline and dementia, but mechanisms remain unclear. The current study examined whether visit-to-visit blood pressure variability is related to CSF Alzheimer’s disease biomarker levels over time, and whether associations differed by APOE ϵ4 carrier status.

Image Courtesy: AARP Through new developments in Alzheimer’s research, UCI scientists have uncovered evidence of P522R, a particular gene mutation that may aid in minimizing the risk of developing Alzheimer’s disease. Alzheimer’s disease is a progressive disorder that slowly deteriorates memory and thinking skills in the brain, eventually leading to a loss in the ability to complete simple tasks such as  facilitating a conversation or responding to a stimulus in the environment. With the discovery of the disease in 1906 by Dr. Alois Alzheimer, its causes today are focused on two suspects: plaques and tangles in proteins. Beta-amyloid, fragments of…

The Washington Post - April 7, 2022 The FDA approval of Aduhelm ignited a raging debate, with many doctors saying they would not prescribe the drug and several insurers declining to pay for it. Yet even with the uncertainty surrounding the drug, said Elizabeth Head, , at the University of California, Irvine, it is understandable why some families, especially those in which a loved one with Down syndrome faces an all but certain fate, “might believe doing something is better than doing nothing.”

"Much of neuroscience and study of brain diseases has focused on the brain's neurons. This study highlights that in addition to neurons, other brain cells, and especially immune cells, play crucial roles in brain health and disease," said Tallie Z. Baram, distinguished professor in the Departments of Anatomy & Neurobiology, Pediatrics, Neurology, and Physiology & Biophysics at the UCI School of Medicine. "Neuroimmune interactions are a novel, important avenue to understanding and treating several brain disorders and mental illness and have been linked by other UCI researchers to Alzheimer's disease."

First author Gianna Fote was recently interviewed by the Journal of Cell Science for a newly-published paper. She provided commentary on her team's new findings for UCI MIND: "In our recently published work we studied intracellular trafficking of Apolipoprotein E (APOE), a lipid-carrying protein. The APOE4 isoform of this protein is the biggest genetic risk factor for late-onset Alzheimer’s disease. We found that that APOE can be degraded by a process called autophagy, a process in which cellular waste is transported to an acidic organelle called the lysosome. The APOE4 isoform accumulates in the lysosome and causes increased induction of…

David Sultzer, MD, Professor, Psychiatry & Human Behavior, School of Medicine eturbonews: The Institute for Molecular Medicine (IMM), a non-profit organization dedicated to basic and translational molecular research to develop safe, effective vaccines against #Alzheimers disease and other #neurodegenerative disorders, today announced that it was awarded a $12 million grant from the National Institute on Aging (NIA) division of the U.S. National Institutes of Health (NIH)​ to support clinical trials of its beta-#amyloid (Aβ) vaccines based on DNA (AV-1959D) and recombinant protein (AV-1959R) for the prevention of Alzheimer’s disease (AD). In collaboration with the @ucirvine (Principal Investigator, David Sultzer, M.D.)…

Managed Healthcare Executive - March 17, 2022 According to the CDC, about 5 million Americans have Alzheimer’s disease …. “These numbers are projected to increase because elderly individuals are the fastest-growing segment in the United States,” says Claudia H. Kawas, M.D., a professor in the Department of Neurology at the University of California, Irvine, School of Medicine. … The things known about dementia risk that are potentially modifiable are all related to general health and maintenance of health, says Kawas, noting the association between control of high blood pressure and cholesterol levels and a lower risk of dementia.

90+ Study: Learning from the oldest-old Researchers can learn a lot about how Alzheimer’s develops by studying people at increased risk. People older than age 90, or the oldest-old, are the fastest growing segment of the population in the United States and most of the world and have the highest rates of dementia. Remarkably, the oldest-old also have the highest rate of cognitive resilience and somehow avoid developing dementia despite having brain pathologies. This populations’ high rates of dementia, yet also resilience, make it an optimal group to study to understand the underlying causes of dementia. The 90+ Study, launched in…

The Winter 2022 edition of UCI Magazine features UCI MIND researchers, including David Sultzer, MD, Michael Yassa, PhD, and more! Read the latest edition of UCI Magazine here >

Discover Magazine: Aging dogs can develop canine cognitive dysfunction (CCD), sometimes known as “doggie dementia.” The brains of dogs with CCD show only amyloid beta plaques, not tau tangles, but their symptoms are similar to the symptoms of dementia in humans, explains Elizabeth Head, director of the graduate program in experimental pathology at the University of California, Irvine. “They’ll forget how to signal that they need to go out,” Head says. “In the more severe stages of the disease, they can become incontinent and may not recognize people.” She points out that because dogs live closely with humans, any behavioral changes…

Contributed by Hayk Davtyan, Ph.D. and Christel Claes, Ph.D. While the word “mutation” may conjure up alarming notions, a mutation in brain immune cells serves a positive role in protecting people against Alzheimer’s disease. Now UCI MIND biologists have discovered the mechanisms behind this crucial process. Their paper appears in the journal Alzheimer’s and Dementia. The investigation centered on a variant of the PLCG2 gene, which makes the instructions for producing an enzyme important to brain immune cells called microglia. “Recently the mutation, which is known as P522R, was shown to lower the risk of developing late-onset Alzheimer’s,” said Hayk…

Renewal recognizes UCI's dedication to patient care and active engagement in research to develop new therapeutic approaches February 15, 2022 “Renewal of certification as a Huntington’s Disease Society of America Center of Excellence is very exciting, as this will help us expand our patient care and research. HD was one of the first diseases for which a genetic cause was determined and serves as a paradigm for research into other such diseases,” says Leslie Thompson, Ph.D., Donald Bren and Chancellor’s professor in the departments of psychiatry and human behavior and biological chemistry at the UCI School of Medicine. UCI has…

UCI MIND #InTheNews: Forbes: "According to UCI, the new center will involve collaborations across seven areas: SMART (statistics, machine learning-artificial intelligence) designs software to integrate and analyze health records, molecular data, and observation. This unit will be led by Daniel Gillen, professor and chair of statistics, and Zhaoxia Yu, associate professor of statistics... Precision omics generates, analyzes, and administers genomic, proteomic, and chemical data. It’s led by Suzanne Sandmeyer, professor of biological chemistry, and Leslie Thompson, the Donald Bren and Chancellor's Professor of psychiatry & human behavior at UCI... The institute will take special aim at diseases that heretofore have lacked effective treatments. “For many…

UCI MIND #InTheNews   @Seniors Matter - Feb. 9, 2022 “People who engaged in more healthy behaviors had a lower risk than people with fewer because all of these things matter, and when it comes to brain-healthy behaviors, more is more!” said Joshua Grill, PhD, a professor of psychiatry and human behavior at the University of California, Irvine. “So, we should all try to adopt as many brain-healthy behaviors as we can.”

Our memories are imperfect treasures – dear to our hearts, but not necessarily accurate snapshots of reality. CNN's Chief Medical Correspondent Dr. Sanjay Gupta talks to neurobiologist Michael Yassa about how memories are stored in the brain, why we forget, and what we’ve gotten wrong about how it’s supposed to work. To help understand the mechanisms of memory, we meet a woman who remembers absolutely everything... and a man who can’t even recall what he ate for breakfast. Plus, actionable tips for how we can keep our memories sharp at any age.

Originally posted on The Company of Biologists "First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping early-career researchers promote themselves alongside their papers." UCI MIND trainee Gianna Fote was recently selected for an interview to discuss her latest publication. Read the full interview here, and learn about her publication here.

As a child in the early 1980s, I was enamored with My Little Pony, the colorful plastic horse figurines with long manes. I also had the brand’s Show Stable, which was parked in our TV room and filled with my beloved ponies. But as I progressed through grade school, I eventually packed up my stable and forgot about the toys I once loved.   By late 2003, I hadn’t thought about my ponies for over 15 years. Then, VH1 ran a 1980s nostalgia show in which celebrities reminisced about bygone pop culture. An actress held up a My Little Pony figurine…

Overactivity in the hippocampus, likely tied to lack of inhibition, underlies some age-related cognitive decline. Targeting those circuits shows early promise in slowing memory loss. By Emily Singer December 9, 2021 As we get older, our memory begins to fail in predictable ways. We’re more likely to confuse similar memories, for example, forgetting whether it was little Tim or Samantha who threw the turkey leg across the room at Thanksgiving, and whether that happened the same year the dog snatched the sweet potato pie. In experiments in the lab, old people can easily remember very different objects but have a…

UCI MIND In The News: Dec 3 is International Day of Persons with Disabilities. So congratulations to Dr. Elizabeth Head of University of California, Irvine -- Recognized as an Expertscape World Expert in Intellectual Disability: https://expertscape.com/ex/intellectual+disability

While aging is typically associated with cognitive decline, some individuals are able to diverge from the characteristic downward slope and maintain very high levels of cognitive performance. Prior studies have found that cortical thickness in the cingulate cortex, a region involved in information processing, memory, and attention, distinguish those with exceptional cognitive abilities when compared to their cognitively more typical elderly peers. Others major areas outside of the cingulate, such as the prefrontal cortex and insula, are also key in successful aging well into late age, suggesting that structural properties across a wide range of areas may better explain differences…

A blood test may be able to identify individuals at increased risk for developing Alzheimer’s disease symptoms, according to research presented at the Clinical Trials on Alzheimer’s Disease conference. The results came as part of the AHEAD study. Joshua D. Grill “The goal of this study is to stop Alzheimer’s disease before it begins — delaying or preventing symptoms in people at increased biological risk,” Joshua D. Grill, PhD, recruitment unit co-chair for the Alzheimer’s Clinical Trials Consortium, which helps oversee the AHEAD Study Recruitment and Retention Working Group, told Healio Psychiatry. “The latest advance is to use a blood test to improve the…

Overall, this nice series of experiments identifies yet another component of the sleep/wake regulatory system—the TRN—that is disrupted by Aβ and degenerated in AD. It is interesting that stimulating the TRN can impact Aβ. It is unlikely, however, that the TRN is the only stimulation target necessary, and that stimulating it would address all the sleep disruptions caused by Aβ and also tau pathology. AD pathophysiology impacts multiple different systems regulating sleep, including brainstem and hypothalamic nuclei, cortical nodes regulating slow wave expression, and even the hippocampus that regulates ripples, and coupling of slow waves, sleep spindles, and ripples. This…

Certain antihypertensive medications, particularly diuretics, are linked to lower Alzheimer's disease neuropathology (ADNP) and other brain disease processes, new research shows.