Highlights
Published Papers
Once a researcher has completed their work, they document the details and outcomes of their study and submit the paper for publication in a science journal. The paper is peer reviewed by scientists to validate the methods and information and, if approved, gets published so the results can be shared with the world. Cure Alzheimer’s Fund tracks published papers as one key measure of success for research grants that we funded.
In 2023, 183 peer-reviewed papers that acknowledged support from Cure Alzheimer’s Fund were published in prominent scientific journals, more than in any year before. Since our inception in 2004 through Dec. 31, 2023, the total number of published papers acknowledging CureAlz funding is 1,177. These published papers collectively have been cited by other researchers in support of their own work 97,674 times.
Here are a few select highlights from papers published resulting from CureAlz-funded research in 2023.
Unlocking the Brain’s Immune Gateways—The Role of Skull Channels in Neuroimmune Communication
The central nervous system (CNS), made up of the brain and spinal cord, has a specialized immune system that historically has been considered isolated from the immune system that serves the rest of the body. However, recent research has challenged this idea by demonstrating an intricate relationship between the two systems. Newly discovered skull channels connect bone marrow within the skull with the protective layers surrounding the brain, suggesting that the bone marrow contributes white blood cells to guard the CNS. Read more here.
Published in Nature Neuroscience: “Skull bone marrow channels as immune gateways to the central nervous system”
Jonathan Kipnis, Ph.D., Washington University School of Medicine in St. Louis, and Matthias Nahrendorf, M.D., Ph.D., Massachusetts General Hospital; Harvard Medical School
Exercise and Alzheimer’s Disease: The Protective Power of Irisin*
Using a 3D cell culture model that generates Alzheimer’s disease pathology, scientists discovered that the hormone irisin, which is released from the muscles during exercise, increases the production of neprilysin in specific brain cells known as astrocytes. Upon its release from astrocytes, neprilysin breaks down amyloid beta, the protein that forms harmful plaques in AD. In these experiments, exposure to the exercise-triggered hormone irisin led to significant reduction in amyloid beta levels. Read more here.
Published in Neuron: “Irisin Reduces Amyloid-ß by Inducing the Release of Neprilysin from Astrocytes Following Downregulation of ERK-STAT3 Signaling”
Joseph Park, Ph.D., Luisa Quinti, Ph.D., Doo Yeon Kim, Ph.D., Christiane Wrann, D.V.M, Ph.D., Rudolph Tanzi, Ph.D., and Se Hoon Choi, Ph.D., Massachusetts General Hospital; Harvard Medical School
*Research has highlighted the benefits of exercise for brain health, including for Alzheimer’s disease. The discovery of the hormone irisin and its interaction with amyloid plaques is one mechanism for exercise’s positive impact.
The Brain’s Blood Vessels Change in Alzheimer’s Disease
Changes in the blood vessels of the brain have been linked to Alzheimer’s disease (AD), and deterioration of the blood-brain barrier may be an early sign of the disease. A study profiling gene expression of the brain’s blood vessels revealed AD changes in unprecedented detail. The results provide a map to guide future therapies targeting blood-brain barrier dysfunction in Alzheimer’s. Read more here.
Published in Nature Neuroscience: “Single-nucleus multiregion transcriptomic analysis of brain vasculature in Alzheimer’s disease”
Li-Huei Tsai, Ph.D., and Manolis Kellis, Ph.D., Massachusetts Institute of Technology; Broad Institute
Role of T Cells in Alzheimer’s Disease Identified
With age and cell damage, microglia can shift from protective to destructive.
A new study reveals that mice with loss of brain tissue caused by toxic tau, similar to that in Alzheimer’s, have more destructive T cells, generally resident in the periphery of the body, in their brains, attracted there by the brain-resident microglia. Understanding the role of these circulating immune cells in neurodegeneration may lead to new areas of therapeutic strategies. Read more here.
Published in Nature: “Microglia-Mediated T Cell Infiltration Drives Neurodegeneration in Tauopathy”
Jasmin Herz, Ph.D., Jonathan Kipnis, Ph.D., Jason D. Ulrich, Ph.D., and David M. Holtzman, M.D., Washington University School of Medicine in St. Louis
“CureAlz funds accelerated discovery in the type of research we do, speeding up to find answers to the questions we are asking.”
—LIISA GALEA, PH.D.
Why Are Some People Resilient to Alzheimer’s Disease Pathology?
Despite high levels of amyloid beta plaques and tau tangles in their brain, some individuals never develop symptoms of dementia in their lifetime. Resilience to pathology leading to Alzheimer’s disease may be associated with reduced levels of neuroinflammation, preserving synapses and staving off neurodegeneration. This study suggests that in cases with symptoms of Alzheimer’s disease, neuroinflammation may be triggered by an unusual abundance of toxic tau oligomers in synapses that serve as an “eat me” signal to microglia and astrocytes. In contrast, resilient brains show lower levels of tau oligomers and preserved synapse numbers. Read more here.
Published in JAMA Neurology: “Tau Oligomer-Containing Synapse Elimination by Microglia and Astrocytes in Alzheimer Disease”
Teresa Gomez-Isla, M.D., Massachusetts General Hospital; Harvard Medical School, and Karen E. Duff, Ph.D., University College London, England
Insights from the Aging Mouse Brain
This investigation set out to identify the molecular underpinnings of aging in the brain. It discovered that previously unsuspected regions of the brain are especially vulnerable to aging, and that two anti-aging treatments can rejuvenate the brain in unexpected ways. Read more here.
Published in Cell: “Atlas of the Aging Mouse Brain Reveals White Matter as Vulnerable Foci”
Tony Wyss-Coray, Ph.D., Stanford University
Does a Genetic Mutation Prevent Alzheimer’s Disease?
In a study exploring the interaction between genetics and Alzheimer’s disease pathology, researchers discovered how the APOE3 Christchurch (APOE3ch) mutation protects against Alzheimer’s disease. The findings showcase how APOE3ch revs up the efficiency of microglia surrounding amyloid plaques to remove aggregated tau and has the ability to prevent the spread of tau, which precedes neuronal death and dementia. Read more here.
Published in Cell: “APOE3ch Alters Microglial Response and Suppresses Aß-Induced Tau Seeding and Spread”
Marco Colonna, M.D., Jason D. Ulrich, Ph.D., and David M. Holtzman, M.D., Washington University School of Medicine in St. Louis
The First Biomarker for Tau Tangles
Researchers have identified a promising biomarker, MTBR-tau243, that could transform the early detection of Alzheimer’s disease. The strong association of MTBR-tau243 with tau pathology and cognitive decline positions it as a prime candidate for diagnosing Alzheimer’s disease, tracking its advancement and evaluating tau-targeted therapies. bit.ly/3U8xIEy
Published in Nature Medicine: “CSF MTBR-tau243 is a specific biomarker of tau tangle pathology in Alzheimer’s disease”
David M. Holtzman, M.D., and John C. Morris, M.D., Washington University School of Medicine in St. Louis; Rik Ossenkoppele, Ph.D., Amsterdam University Medical Center, The Netherlands; Lund University, Sweden; Oskar Hansson, M.D., Ph.D., Lund University, Sweden; Randall J. Bateman, M.D., Washington University School of Medicine in St. Louis
“Funding from Cure Alzheimer’s Fund helped my lab make some important discoveries that have now launched a major area of research for us and led to several NIH grants, as well as a new drug discovery effort. So, the impact has been huge.”
—ERIK S. MUSIEK, M.D., PH.D.