A Novel Test for Alzheimer’s Disease Based on DNA Circulating in Blood

We propose to establish a novel type of blood test, based on circulating DNA fragments, to identify and monitor brain cell death in in patients developing Alzheimer’s disease.

Aim 1: to establish a method for sensitive and specific detection of DNA derived from Alzheimer’s disease-relevant tissues, using DNA methylation patterns. Aim 2: to determine baseline levels of brain, vascular and immune cell-free DNA in the blood of 300 healthy volunteers, ages 50-80. Aim 3: to determine levels of Alzheimer’s disease-relevant DNA markers in the blood of healthy donors (n=150) patients with Alzheimer’s disease (n=150) as well as people with mild cognitive impairment who have (n=75) or haven’t (n=75) developed dementia in the 2 years that followed blood drawing. Diagnostic medicine is being transformed by liquid biopsies, which monitor fragments of cell-free DNA (cfDNA) released from dying cells to blood. We have developed an approach for detecting the tissue origins of cfDNA molecules, using cell type-specific DNA methylation patterns, which are a stable and universal mark of cell identity. This opens the way for liquid biopsy detecting cell death in specific cell types, including brain, additional Alzheimer’s-relevant tissues such as the vasculature, and inaccessible processes such as brain inflammation. The long-term outcome of the project will be a novel, sensitive and specific blood test for assessment of cell death in the brain and additional tissues relevant for Alzheimer’s disease. This will bring us closer to a blood test that can reliably detect Alzheimer’s disease in its earliest stages. About the Researcher: Yuval Dor, PhD, is a professor of biology at the Hebrew University-Hadassah Medical School. He earned his PhD in vascular biology at the Hebrew University in 2001 with Prof. Eli Keshet, and trained as a post-doc at Harvard University with Doug Melton until 2004. His lab studies postnatal tissue dynamics: the molecular mechanisms by which cells regenerate and die. Much of his work focuses on pancreatic beta-cells in the context of diabetes, as well as on pancreatic cancer. In recent years he has developed a novel blood test to study cell death in humans, using methylation signatures of cell-free circulating DNA. This new type of liquid biopsy opens a minimally-invasive window into tissue dynamics in health and in pathologies including cancer, infection and neurodegeneration, including the detection of brain cell death in Alzheimer’s disease. Since 2017 he serves as the chair of biology and medicine at the Israel Science Foundation.

Diagnostic medicine is being transformed by liquid biopsies, which monitor fragments of cell-free DNA (cfDNA) released from dying cells to blood. We have developed an approach for detecting the tissue origins of cfDNA molecules, using cell type-specific DNA methylation patterns, which are a stable and universal mark of cell identity. This opens the way for liquid biopsy detecting cell death in specific cell types, including brain, additional Alzheimer’s-relevant tissues such as the vasculature, and inaccessible processes such as brain inflammation.

The long-term outcome of the project will be a novel, sensitive and specific blood test for assessment of cell death in the brain and additional tissues relevant for Alzheimer’s disease. This will bring us closer to a blood test that can reliably detect Alzheimer’s disease in its earliest stages.