This new initiative, administered by the Brain Immunology & Glia (BIG) Center at Washington University School of Medicine, invests in core activities of the Center, supports a new BIG Center seed grant program, and funds three lead projects conducted by David Holtzman; MD, Jonathan (Jony) Kipnis, PhD; and Marco Colonna, MD.  These projects make up some of the most exciting and promising avenues of research in the areas of neurodegeneration and neuroimmunology.

A transformational gift from the Carol and Gene Ludwig Family Foundation established The Carol and Gene Ludwig Center for Research on Neurodegeneration at Columbia University’s Vagelos College of Physicians and Surgeons (VP&S). The Center supports research to better understand the underlying biological and genetic mechanisms of Alzheimer’s disease and related disorders and to discover innovative and more effective, targeted treatments for these diseases.

The gift will help create state-of-the-art laboratories for the Center and Ludwig Investigators in the new Vagelos Innovation Laboratories research building at Columbia. A cornerstone of the Center are pilot awards designed to advance and accelerate innovative new research projects, with seed funding for especially promising areas of investigation. The gift also will help Columbia recruit and retain top scientists working on neurodegeneration and funds an annual symposium for the exchange and stimulation of ideas and results among the most prominent researchers in the field.

In 2024, Yale University Medical School started the Carol and Gene Ludwig Program for the Study of Neuroimmune Interactions in Dementia to advance innovative research, facilitate the sharing of ideas, data and knowledge towards biomedical understanding and therapeutics focused on combatting Alzheimer’s disease and related dementias.  The Program includes recruitment of a new faculty member, monthly seminars and a seed grant program.

The Ludwig Program is led by co-directors Stephen Strittmatter, MD, PhD, Vincent Coates Professor of Neurology and chair and professor of neuroscience; director of the Kavli Institute for Neuroscience; director of Cellular Neuroscience, Neurodegeneration & Repair; director of the Memory Disorders Clinic; and director of the Yale Alzheimer's Disease Research Center; and Lauren Sansing, MD, professor of neurology and of immunobiology, and vice chair in the Department of Neurology for Academic and Faculty Affairs.

The primary focus of the Liddelow lab is on understanding the complex roles of astrocytes in the brain. Astrocytes are a type of glial cell that play crucial roles in maintaining brain homeostasis, supporting neuron function, and responding to injury. The lab is particularly centered on a subtype of reactive astrocytes they discovered, which release toxic factors capable of killing specific neurons. "Support from the Gene and Carol Ludwig Family Foundation supports our work into understanding the mechanisms that enable recovery of these reactive astrocytes back to a neuron supporting physiologically normal state. Targeting astrocytes in diseases like Alzheimer's is an untapped opportunity to help millions of patients worldwide."

The Clelland lab at the UCSF Weill Institute for Neurosciences develops novel therapies for neurodegenerative diseases. Her current work centers on creating novel CRISPR gene therapies for genetic forms of neurodegenerative diseases such as frontotemporal dementia (FTD), Alzheimer's disease (AD), Parkinson's disease (PD) and amytrophic lateral sclerosis (ALS)."CGLFF is advancing our gene therapy for Alzheimer's disease and bold, novel CNS delivery strategies and platforms.”

The Foundation provided a grant to Harvard Medical School (HMS) to establish the Ludwig Neurodegenerative Disease Seed Grants Program to advance early-stage research toward treatment approaches. The Program was born of the many challenges that scientists have encountered in developing therapies for neurodegenerative diseases, especially Alzheimer’s disease. The program strives to identify projects grounded in basic biology that have solid potential for translational impact.

In this 4-year program, 2-3 grant recipients are selected each year through a competitive review process. The goal of this program is to leverage the in-depth basic neuroscience expertise at Harvard to investigate and validate novel mechanisms that could be key underlying drivers of neurodegeneration and in particular, Alzheimer’s disease. In addition to advancing research on neurodegenerative diseases, the program also aims to create a stronger research community around neurodegeneration at HMS. Awardees will share their findings at symposia, journal clubs, and other gatherings open to the broader HMS community.

The mission of the Ramirez lab is twofold: to reveal the neural circuit mechanisms of memory storage and retrieval, and to artificially modulate memories to combat maladaptive states. The lab will do so in a multi-disciplinary fashion by combining virus engineering strategies, immunohistochemistry and physiology, optogenetics and functional imaging of targeted populations in vivo, and a battery of behavioral assays.

“Funding from the LFF has helped us embark on the kinds of high-risk high-reward projects in the lab that otherwise would have been impossible! The LFF has directly contributed to the growth and development of several lab members, including graduate students and post-docs, all who have made exceptional progress in delineating the neural mechanisms of learning and memory, as well as restoring health back to the diseased brain.”

Dr. Xiao’s laboratory focuses on epigenetic regulation in pluripotent stem cells, including embryonic stem cells and induced pluripotent stem cells (iPSC). His laboratory has made significant contributions to the understanding of the maintenance of pluripotency, as well as the recent discovery of novel epigenetic mechanisms, i.e., N6-methyl-adenine, in mammalian genomes.

“We greatly appreciate the support from the Carol and Gene Ludwig Family Foundation for Carol’s extraordinary vision and perspective in science.  Their support is essential for the success of my lab and instrumental for our endeavor to discover hidden components in the human genome.”

Dr. Ho’s laboratory has been engaged in HIV research since the beginning of the AIDS pandemic, initially focusing on clinical virology and select topics in HIV pathogenesis. In 2020, since the COVID-19 pandemic began, the laboratory has begun investigating potential treatments and vaccines for SARS-CoV-2 coronavirus infection.

The goal of Dr. De Jager's work as a clinician-scientist is to apply modern methods of neuroimmunology, statistical genetics, and systems biology to the understanding of common neurodegenerative diseases such as Alzheimer’s disease and Multiple Sclerosis. He is working to harness the immune system to ensure healthy brain aging. Thanks to the Carol and Gene Ludwig Family Foundation, he is developing tools with which to map the trajectory of immune aging in each individual; this will yield a personalized approach to assessing the state of each individual’s immune system and the likelihood of continued brain health with advancing age.

The King laboratory is interested in the fundamental mechanisms that control nuclear mechanics, dynamics, and quality control. Major efforts in the lab include: Developing a quantitative model for the mechanical response of the nucleus, investigating how nuclear compartments and local chromatin state influence genome integrity mechanisms, defining how the genome is organized over time in single cells, and defining contexts in which direct mechanotransduction of force through the LINC complex regulates cell function and homeostasis.

The overall goal of Dr. Yankner’s research is to achieve a greater understanding of the molecular basis of brain aging and how normal aging transitions to pathological aging, giving rise to neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease.

“Continued support from the Ludwig Family Foundation has led to novel therapeutic approaches that are focused on the preservation of cognitive function during aging. This multi-disciplinary effort would be difficult to sustain through traditional grant funding mechanisms.  As such, the Ludwig Family Foundation plays an important role in pushing the boundaries of neurodegenerative disease research at Harvard.”