Non-Oncology Applications: 5 of 14

Neurological Disease

Diseases of the brain and nervous system include stroke, head injury, epilepsy, multiple sclerosis, brain tumors, Alzheimer's disease, Parkinson's disease, and other degenerative conditions. These disorders can be profoundly disabling, and the brain is one of the hardest organs in the body to sample directly.

Part of the reason is the blood-brain barrier, a tightly controlled boundary between brain tissue and the bloodstream. It helps keep the brain's chemistry stable and blocks many harmful substances from entering. It also means that relatively little material from the brain reaches the blood, so disease signals can be faint. Taking a piece of brain tissue is rarely an option either. Unlike a tumor in another organ or a transplanted kidney, the brain generally cannot be biopsied just to clarify a diagnosis.

That makes a blood test appealing. In many neurological diseases, there is no easy tissue sample to fall back on.

There is one closer sample: the fluid surrounding the brain and spinal cord. Doctors can collect it with a needle in the lower back. Because that fluid sits near the brain, it contains more brain-derived material than blood and is widely used in research. People understandably do not want repeated spinal taps, though, so researchers often try to move the same measurements into blood.

The materials include loose DNA released by dying brain cells, short RNA pieces linked to particular brain cell types, packages of material released by cells, and circulating proteins. For brain tumors, researchers want to find the tumor's genetic faults without brain surgery. After a stroke or head injury, they want a quick measure of how much damage has occurred. For degenerative disease, the hope is to detect the process years before symptoms appear, when treatment would have more time to help.

The weak signal remains the basic problem. A marker can be higher on average in people with a disease and still overlap so much with healthy people that it is not useful for one patient. Telling two neurological diseases apart is harder again, and that is often the question a doctor actually needs answered.