A Scientist’s 10-year Odyssey to Find Funding for Important, Out-of-the-Box Research
Cure Alzheimer’s Fund has, as a founding principle, a commitment to funding innovative research ideas that may not meet the criteria for funding from the National Institute of Health. Curing Alzheimer’s disease will require audacious ideas that tackle disease mechanisms by leaving no stone unturned. A recent article in STAT tells the story of the 10-year odyssey that Dr. Rob Moir of Massachusetts General Hospital encountered while trying to find funding for an unconventional theory. The story highlights how he ultimately received a $500,000 grant from Cure Alzheimer’s Fund to pursue his hypothesis. His hunch that inflammation played a more critical role in synapse loss and cell death during Alzheimer’s disease than beta-amyloid accumulation was validated through this research.
Robert Moir | Ph.D. & Rudy Tanzi | Ph.D.
The New York Times Asks: “Will We Ever Cure Alzheimer’s?”
To mark the 40th anniversary of the Science section of The New York Times, the editors made a list of their 11 most pressing science questions they would like answered in the coming years. Given the scale of Alzheimer’s diagnosis in the United States, it is no surprise that the question, “Will we ever cure Alzheimer’s?” featured prominently on their list of most pressing questions. The article featured the perspectives of researchers who have received grants from Cure Alzheimer’s Fund including Dr. John Morris the Director of the Charles F. and Joanne Knight Alzheimer’s Disease Research Center at Washington University School of Medicine in St. Louis, Dr. Sam Gandy, a member of the Cure Alzheimer’s Fund Research Leadership Group and the Associate Director of the Mount Sinai Alzheimer’s Disease Research Center, and Dr. Rudy Tanzi, Chair of the Cure Alzheimer’s Fund Research Leadership Group.
Sam Gandy.| M.D., PH.D., John Morris | PH.D., & Rudy Tanzi | PH.D.
A New Discovery: The Brain Has a Drain to Remove Debris
In healthy humans, the cerebrospinal fluid (CSF) is renewed approximately four times a day. In aging adults, impaired function of lymphatic vessels in the meninges can lead to accelerated accumulation of toxic amyloid beta protein in the brain. The meninges are made up of membranes that line the skull in order to protect the brain and spinal cord. The existence of these lymphatic vessels in the meninges was first mentioned toward the end of the 18th century, but it took more than 200 years for the hypothesis to be confirmed using state of the art imaging technology in the laboratory of Dr. Jonathan (Jony) Kipnis.
In the 30th Anniversary Issue of Neuron, Dr. Kipnis along with his collaborators Drs. Sandro Da Mesquita and Zhongxiao Fu put forth their perspective on the relevance of the meningeal lymphatic system for cerebral spinal fluid drainage, aging-associated brain dysfunction, and amyloid beta clearance in Alzheimer’s disease.
Jonathan Kipnis | Ph.D.
Expanding Our Understanding of the Role of Bace1
New research brings to light cautionary evidence that clinical trials targeting complete inhibition of the enzyme BACE1 may have unintended consequences. BACE1 (β-site amyloid precursor protein cleaving enzyme 1) produces the Aβ42 peptide which, when produced excessively, forms amyloid plaques—one of the hallmarks of Alzheimer’s disease. Inhibition of BACE1 has been actively pursued as a drug target. In this study, the researchers asked the question: what role does BACE1 play in the body outside of Aβ42 production? The scientists uncovered a critical role for BACE1 in regulating the growth of new brain cells.
Se Hoon Choi | PH.D., Doo Yeon Kim | PH.D., & Rudy Tanzi | PH.D.
Get More Sleep!
Sleep is an important aspect of brain health: during sleep, the brain activates cleaning and removes debris. Since 2008, Cure Alzheimer’s Fund has been providing grants to researchers who have investigated the impact of sleep to the brain and Alzheimer’s disease. For example, Dr. David Holtzman of Washington University in St. Louis discovered that sleep-deprived mice had increased levels of tau, one of the hallmarks of Alzheimer’s disease pathology. Erik Musiek is studying the proteins and genes that regulate the body’s circadian clock and its impact on Alzheimer’s disease. Geraldine Kress is studying the disruptions in the circadian system that occurs prior to the clinical onset of memory deficits in Alzheimer’s disease.
Matthew Walker, PhD, is a neuroscientist at Berkeley who studies sleep and has written a book titled Why We Sleep: Unlocking the Power of Sleep and Dreams and offers key insights into how sleep is the most powerful tool we have for promoting health and well being. This is not work funded by our organization but it does provide important insights worth reading.
David Holtzman | M.D., PH.D., Erik Musiek | M.D., PH.D., & Geraldine Kress, PH.D.
Algorithms Are Aiding the Diagnosis of Alzheimer’s Disease
Machine learning is the study of algorithms and mathematical models that scientists rely on to progressively improve their performance on a specific task; these algorithms have the potential to provide a computational framework for predicting who will get Alzheimer’s disease.
Being able to identify those patients with memory impairments who are most likely to decline towards Alzheimer’s disease would be a valuable tool in early diagnosis. Predictions are complicated by the heterogeneity of the subject population as well as the complexity of clinical data that includes cognitive assessments, imaging, and MRI data, as well as genetic and demographic information. Machine learning could potentially provide a computational framework for predicting who will get Alzheimer’s disease with the hope that the diagnosis would happen earlier.
Manolis Kellis | PH.D.
Transparencies About Drug Failures May Accelerate Research
A recent opinion piece published in Nature argues for transparency and open discussion when evaluating the reasons behind drug failures in clinical trials for Alzheimer’s disease. The piece includes a link for recommended guidelines for clinical trial design as well as potential data-sharing initiatives.