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.