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Imaging facilities share $3 million Alzheimer’s research grant

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Imaging facilities share $3 million Alzheimer’s research grant

The Biomedical Imaging Center at the Beckman Institute for Advanced Science and Technology has received $3 million in funding that will help develop diagnostic tools and imaging agents for the early detection of Alzheimer’s disease.

The grant is one of the first federal grants to bridge Beckman’s Magnetic Resonance Imaging Laboratory and Molecular Imaging Laboratory, which are both part of Beckman’s Biomedical Imaging Center.

A team led by Liviu M. Mirica, Wawryzneic “Wawosz” Dobrucki and Dr Daniel A. Llano received the grant from the U.S. National Institute on Aging of the National Institutes of Health to develop and test multi-modal imaging agents for the detection of Alzheimer’s disease and related dementias.

“I’m really excited about the opportunity to collaborate with different scientists from different fields,” said Mirica, a synthetic chemist and the William H. and Janet G. Lycan Professor of Chemistry in the School of Chemical Sciences at the University of Illinois Urbana-Champaign. His research group specializes in building and characterizing synthetic inorganic molecules in vitro: outside of the body.

“I’m looking forward to high-resolution imaging of the brain and its structures,” Dobrucki said, who is the Neil and Carol Ruzic Scholar for Biomedical and Translational Sciences, is an imaging expert who works extensively with PET scanning in Beckman’s Molecular Imaging Laboratory.

Llano, a professor of molecular and integrated physiology and a physician-surgeon, is a practicing neurologist who sees patients daily and specializes in in vivo brain studies: those inside the body.

“The potential impact that this project will have on Alzheimer’s is what I’m most excited about,” Llano said.

Understanding Alzheimer’s disease

Alzheimer’s disease is a neurodegenerative disease that negatively affects brain function and cognitive abilities. Along with Parkinson’s disease, amyotrophic lateral sclerosis, and other disorders, Alzheimer’s falls under the category of amyloid diseases. Amyloids are small groups of abnormally fibrous or misfolded proteins that do not commonly serve a purpose in the body.

A key marker of Alzheimer’s disease is the presence of amyloid plaques: large buildups of smaller beta-amyloid peptide aggregates. Peptides are short chains of amino acids that eventually create proteins. Neuroinflammation and oxidative stress in the brain are also major markers of Alzheimer’s.

The detection and treatment of neurodegenerative diseases is especially difficult because of the blood-brain barrier, a semipermeable system of blood vessels and capillaries that controls the flow of ions, molecules, and cells between the blood and the brain.

To be effective, imaging agents and drug therapies, which are made of molecules or antibodies, need to be able to pass through.

Diagnosis and treatment

Diagnosing Alzheimer’s disease with a high degree of accuracy requires identifying the amyloid aggregates and can only be completed during post-mortem investigation. This creates a need for diagnostic tools that can quickly locate soluble beta-amyloid peptide aggregates and larger amyloid plaques in a living patient.

PET and MRI are two noninvasive imaging methods commonly used in clinical settings, however, no MRI contrast agents that target amyloid aggregates have been developed.

The few FDA-approved PET imaging agents are insufficient at detecting small-scale amyloid abnormalities or in some cases, lead to false-positives test results when diagnosing Alzheimer’s.

Mirica emphasised the importance of developing diagnostic tools to target smaller beta-amyloid peptides and other signs of neuroinflammation and oxidative stress for a variety of reasons.

Creating multi-modal tools that can be used for both PET and MRI scans will give researchers a better idea of who is at risk for developing Alzheimer’s, who truly has the disease, and at what stage.

The $3M plan

Mirica, Dobrucki, and Llano will receive the $3 million grant over the course of five years to generate novel dual-purpose imaging agents that can easily pass the blood-brain barrier and are compatible with both PET and MRI scanners.

This will enable the detection of neurodegenerative diseases at earlier stages and “will help tremendously in developing better therapies,” Mirica said.

Brad Sutton, a professor of bioengineering and the technical director of Beckman’s Biomedical Imaging Center, will assist the team by performing in vivo MRI studies. They will then evaluate the imaging agent’s ability as a dual modality diagnostic agent for Alzheimer’s disease and related dementias.

Already, Mirica and his collaborators have developed a series of customised molecules that can cross the blood-brain barrier and help detect both smaller soluble beta-amyloid peptides and larger insoluble amyloids.

They have also developed a copper-based PET imaging agent that led to the successful imaging of amyloid plaques in transgenic Alzheimer’s mice.

Looking ahead, the team believes that these agents can be developed to pass through the blood-brain barrier in humans and image multiple markers of Alzheimer’s disease and other neurodegenerative diseases at earlier stages.

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Tai chi outperforms conventional exercise for seniors

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New findings from 12 studies involving 2,901 participants have demonstrated that tai chi outperforms conventional exercise in improving mobility and balance in seniors.

While tai chi is understood to be beneficial for functional mobility and balance in older adults, such benefits are not well understood due to large variance in research study protocols and observations.

This new review and analysis has now shown that tai chi can induce greater improvement in functional mobility and balance in relatively healthy older adults compared to conventional exercise.

The findings showed the following performance results:

  • The time to complete 50-foot walking was 1.84 seconds faster. 
  • The time to maintain a one-leg stance was 6 seconds longer when eyes were open and 1.65 seconds longer when eyes were closed. 
  • Individuals improved their timed-up-and-go test performance by 0.18 points, indicating quicker standing, walking, and sitting.
  • Individuals taking the functional reach test showed significant improvement with a standardised mean difference of 0.7, suggesting a noteworthy positive impact on the ability to reach and perform daily activities.

Secondary analyses revealed that the use of tai chi with relatively short duration of less than 20 weeks, low total time of less than 24 total hours, and/or focusing on the Yang-style of this ancient form of Chinese martial arts were particularly beneficial for functional mobility and balance as compared to conventional exercise.

“This systematic literature review and meta-analysis are exciting because they provide strong evidence that tai chi is a more efficient strategy to improve functional mobility and balance in relatively healthy older adults, as compared to conventional exercise,” said Brad Manor, Ph.D., director of the Mobility and Falls Program at Hebrew SeniorLife’s Hinda and Arthur Marcus Institute for Aging Research, and associate professor of medicine, Harvard Medical School and Beth Israel Deaconess Medical Center.

“This research suggests that tai chi should be carefully considered in future studies and routines of rehabilitative programs for balance and mobility in older adults,” said Bao Dapeng, professor at Beijing Sport University.

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New standards for biomarkers of ageing

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A paper has put forward a new framework for standardising the development and validation of biomarkers of ageing to better predict longevity and quality of life.

Led by Harvard researchers, the team has zeroed in on biomarkers of ageing using omic data from population-based studies. 

The team included ageing and longevity expert Alex Zhavoronkov, PhD, founder and CEO of AI-driven drug discovery company Insilico Medicine, and the findings appeared in Nature Medicine

Ageing is associated with a number of biological changes including increased molecular and cellular damage, however, researchers do not yet have a standardised means to evaluate and validate biomarkers related to ageing. 

In order to create those standards as well as actionable clinical tools, the team analysed population-based cohort studies built on omic data (data related to biological molecules which can include proteomics, transcriptomics, genomics, and epigenomics) of blood-based biomarkers of ageing. The researchers then compared the predictive strength of different biomarkers, including study design and data collection approaches, and looked at how these biomarkers presented in different populations. 

In order to better assess the impact of ageing using biomarkers, the researchers found that clinicians needed to expand their focus to consider not only mortality as an outcome, but also how biomarkers of aging are associated with numerous other health outcomes, including functional decline, frailty, chronic disease, and disability. They also call for the standardisation of omic data to improve reliability. 

“Omics and biomarkers harmonisation efforts, such as the Biolearn project, are instrumental in validation of biomarkers of aging” said co-first author Mahdi Moqri, PhD, of the Division of Genetics. 

Biolearn is an open-source project for biomarkers of aging and is helping to harmonise existing ageing biomarkers, unify public datasets, and provide computational methodologies.

The team also emphasised the importance of continued collaborations among research groups on “large-scale, longitudinal studies that can track long-term physiological changes and responses to therapeutics in diverse populations”, and that further work is required to understand how implementation of biomarker evaluation in clinical trials might improve patient quality of life and survival.

“If we hope to have clinical trials for interventions that extend healthy lifespan in humans, we need reliable, validated biomarkers of ageing,” said co-first author Jesse Poganik, PhD, of the Division of Genetics. 

“We hope that our framework will help prioritise the most promising biomarkers and provide health care providers with clinically valuable and actionable tools.”

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Healthy aging research to receive $115 million

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Global non-profit Hevolution Foundation has announced $115 million in funding that makes up 49 new awards under its Geroscience Research Opportunities (HF-GRO) programme.  

As part of Hevolution’s mission to catalyse the healthspan scientific ecosystem and drive transformative breakthroughs in healthy aging, HF-GRO is funding promising pre-clinical research in aging biology and geroscience. 

Through this first wave of HF-GRO awards, Hevolution will invest up to $115 million in this first cohort of 49 selected projects over the next five years. Its second call for proposals under HF-GRO will be announced later this year, offering an additional $115 million to address the significant funding gaps in aging research.  

Dr. Felipe Sierra, Hevolution’s Chief Scientific Officer stated: “These 49 important research projects represent a significant step forward in deepening our understanding of healthy aging. Hevolution’s prime objective is to mobilise greater investment around uncovering the foundational mechanisms behind biological aging. 

“We are steadfast in our belief that by examining the root causes of aging, rather than solely focusing on its associated diseases, we can usher in a brighter future for humanity.” 

HF-GRO awardees include researchers at prestigious institutions across the United States, Canada, and Europe, including the U.S. National Institute on Aging, Brigham and Women’s Hospital, the Buck Institute, the Mayo Clinic, New York University, and the University of California San Francisco, among many others. 

The American Federation for Aging Research is providing programmatic support for the HF-GRO program, with grantees selected through a rigorous two-stage peer-review process involving 100 experts in aging biology and geroscience. 

Dr Berenice Benayoun, an HF-GRO grant recipient at the University of Southern California, stated: “I am extremely honored and excited that Hevolution selected our project for funding. This is a project close to my heart, which aims at understanding why and how the female and male innate immune aging differs. 

“This funding will support us as we start laying the foundation for a lasting improvement of women’s health throughout aging.” 

To date, Hevolution has committed approximately $250 million to transform the healthy aging sector, including the $40 million for specialised research and development in healthspan science recently announced at Hevolution’s Global Healthspan Summit. 

Hevolution is ramping up its investments to enable healthier aging for all and is now the second largest funder of aging biology research worldwide.  

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