The Paul G. Allen Family Foundation announced today the award of Allen Distinguished Investigator (ADI) grants to five teams of researchers with projects that will open new and innovative avenues of research in Alzheimer's disease by uncovering its elusive biological roots. The projects are funded at a total of $7 million over three years.
Alzheimer's disease is the sixth leading cause of death in the United States, impacting an estimated 5.3 million Americans. Currently, someone develops Alzheimer's every 67 seconds, with that number projected to grow to every 33 seconds by 2050 according to the Alzheimer's Association Facts and Figures report.
Despite widespread research into treatments for Alzheimer's disease, there is a staggering 99.6% failure rate in clinical trials to bring new treatments to market.
"We cannot hope to fight Alzheimer's until we understand the basic biology that underlies the onset and progression of disease," says Tom Skalak, Ph.D., Executive Director for Science and Technology for the Paul G. Allen Family Foundation. "The Allen Distinguished Investigator projects will provide crucial fresh direction in Alzheimer's disease research, in part because they include team member perspectives both from within and outside the Alzheimer's field. We know that these kinds of creative, cutting-edge projects will produce new diagnostics, treatments or even cures for this devastating disease."
Through the ADI program, the Foundation seeks to open new frontiers in science by supporting early-stage research that incorporates novel, creative and ambitious approaches with the potential to reinvent entire fields. The call for proposals in Alzheimer's research focused on generating insight into the basic biological foundations of Alzheimer's, with an emphasis on cell biology, and called for multidisciplinary teams that included researchers with a background in Alzheimer's paired with scientists who bring fresh perspectives from outside the field.
"The Allen Distinguished Investigator program will help pave the way to novel therapeutic strategies for Alzheimer's disease," says Dean M. Hartley, Ph.D., Director of Science Initiatives at the Alzheimer's Association. "The truly effective treatments we have now in cancer and heart disease are due to the discovery science that has unraveled the underlying biology of these diseases."
The ADI projects will investigate novel and budding areas of research in Alzheimer's, including the role of gene combinations, white matter damage, pH and a recently described brain-wide clearance system, while also developing new methods and tools to study basic processes and identify new treatments.
About the ADI Recipients
Allen Distinguished Investigators are passionate thought leaders, explorers, and innovators who seek world-changing breakthroughs. With grants between $1 million and $1.5 million each, the Foundation provides these scientists with enough funds to produce momentum in their respective fields. The new ADI recipients are:
- Ragnhildur Thora Karadottir, University of Cambridge ($1.3 million)
Half of the human brain is white matter—the tissue that surrounds and insulates neurons—but little is known about how white matter damage occurs in Alzheimer's disease and how it influences the spread of the characteristic protein "tangles" and "plaques" we see in brains of Alzheimer's disease patients. This proposal addresses uncharted territory in Alzheimer's disease research, using a combination of new imaging methods, biosensors and cutting-edge models to enable us to identify the role of white matter in Alzheimer's disease progression for the first time. Importantly, as white matter lesions appear prior to symptom onset and can be monitored noninvasively by new MRI scanners, they may be an ideal biomarker and target for early treatment to block Alzheimer's disease.
- Jeff Iliff and William Rooney, Oregon Health and Science University ($1.4 million)
Aging is the strongest risk factor for Alzheimer's disease, yet the age-related changes that render the brain vulnerable to the development of Alzheimer's disease remain unclear. The members of this research team are the pioneers who recently described the "glymphatic system" in animals, which helps to clear plaques and other substances from the brain and is also impaired in the aging brain. This team will use novel methods combined with an established imaging approach to measure the activity of the glymphatic system for the first time in human patients. If successful, this method may be able to provide insight into which patients are vulnerable to the build-up of plaques long before clinical symptoms arise. This could provide a window of treatment opportunities when lifestyle interventions and drug treatments have the greatest opportunity of preventing or delaying Alzheimer's disease.
- Fred "Rusty" Gage, Salk Institute ($1.5 million)
The goal of this research effort is to separate out the role of aging from the role of disease in Alzheimer's disease progression. Dr. Gage will use cutting-edge cell culture methods capable of developing patient-specific neurons, as well as high-throughput RNA sequencing and bioinformatics analysis, to compare changes in gene expression due to age with changes specific to Alzheimer's disease. Since both aging and disease impact neuron function, synapses and network function, this work will provide valuable insights into the role of normal aging in disease progression.
- Aimee Kao, University of California, San Francisco ($1.3 million)
Alzheimer's disease results in the accumulation of characteristic plaques and tangles: collections of proteins in the brain that cannot be dissolved. It is unknown why neurons fail to clean up these so-called "garbage" proteins, and why this risk of failure increases with age. This research will focus on a "pH hypothesis," which suggests that impaired regulation of cellular pH promotes neuronal dysfunction and death in Alzheimer's disease by preventing protein clearance and promoting protein aggregation. This understudied area is key to fully understanding the biology of Alzheimer's disease, and may lead to critical and complementary therapeutic strategies aimed at preventing or curing the disease.
- Michael Keiser, Martin Kampmann and David Kokel, University of California, San Francisco ($1.4 million)
The goal of this research project is to combine three powerful and innovative technologies to the study of gene combinations and drugs that control the formation of plaques and tangles in Alzheimer's disease, with the long-term goal of understanding the network of genes controlling all aspects of Alzheimer's disease. The project will take a big data approach to the problem, and use techniques including: 1) computational analysis of an unprecedented "big data" set of 500,000 triple-screened drug compounds; 2) the massively parallel functional interrogation of all human genes and hundreds of thousands of gene combinations; and 3) high throughput behavioral analysis of gene and drug effects in a novel zebrafish model of Alzheimer's disease.
The potential to optimize laboratory testing and operations with automation and AI