A Bone to Brain Axis Controlling Alzheimer's Disease Progression

Our lab focuses on the idea that different regions of bone are all formed by different skeletal stem cells. These skeletal stem cells each in turn determine the normal behavior and diseases of their respective skeletal sites, including the role of bone in driving tumor metastases and, in recent work, how different bones may be involved in disorders of the brain. It is our vision that this work will ultimately lead to therapies targeting these site-specific skeletal stem cells as a new concept to not only treat bone disorders, but a wider range of systemic diseases with links to the skeleton.

Dr. Greenblatt is a physician-scientist who leads a research program discovering new stem cells in the skeleton and understanding how these skeletal stem cells impact neurodegeneration and neuroinflammation. After completing an MS/BS program at Yale University, he then performed MD and PhD studies at Harvard University, completing his PhD in the laboratory of Dr. Laurie Glimcher. Receiving a NIH Director's Early Independence Award and a Burroughs Wellcome Career Award for Medical Scientists allowed him to transition directly to establishing a research lab after completing residency in pathology at Brigham and Women's Hospital. Currently he is in the department of Pathology and Laboratory Medicine at Weill Cornell Medicine. Highlights of his work include discovery of the stem cell on the outer surface of bones and 2 new stem cells forming the skull. With the recent support of a Pershing Square Sohn Prize for Young Investigators in Cancer Research, his lab has identified a new stem cell forming the vertebrae that contributes to the high rates of breast cancer metastasis to the spine over other skeletal sites. In addition to research, he serves as a pathologist at New York Presbyterian Hospital.

Low bone mass is one of the earliest findings in Alzheimer's Disease, often preceding the development of clinical symptoms. While this has been viewed as just a passive consequence of Alzheimer’s Disease, with the support of the Pershing Square MIND Prize, we will investigate whether low bone mass accelerates disease Alzheimer's Disease progression and neurocognitive decline.

"We know that patients with neurodegenerative disease lose bone and are at risk of fracture, but we suspect that the link between the brain and bone is deeper and that bone impacts the brain just as much as the brain impacts bone. The MIND prize is allowing us to take our work in new directions to establish new pathways for the bone and brain to “talk” to each other and will determine whether these pathways offer new avenues to treat neurodegeneration."

To determine how the skeleton may impact Alzheimer's Disease progression, we still study whether a specific new type of stem cell in the skull regulates neurodegeneration by controlling the entry of immune cells to the brain. We will also study whether osteoporosis drugs have the ability to slow Alzheimer's Disease progression in mouse models. Overall, we anticipate that this project will not only establish a new and surprising link between the skeleton and neurodegeneration, but moreover provide insights into how optimizing bone health may offer a new avenue to slow Alzheimer's Disease progression.

"Impact is establishing new lines of scientific thought that permeate the wider scientific world. This means that making and publishing a scientific discovery is only the beginning."