Blood test detects Alzheimer's damage before symptoms

22 January 2019

A simple blood test reliably detects signs of brain damage in people on the path to developing Alzheimer's disease - even before they show signs of confusion and memory loss. The findings, published in Nature Medicine, may one day be applied to quickly and inexpensively identify brain damage in people with Alzheimer's disease as well as other neurodegenerative conditions such as multiple sclerosis, traumatic brain injury or stroke.

"This is something that would be easy to incorporate into a screening test in a neurology clinic," said Brian Gordon, an assistant professor of radiology at Washington University's Mallinckrodt Institute of Radiology and an author on the study. "We validated it in people with Alzheimer's disease because we know their brains undergo lots of neurodegeneration, but this marker isn't specific for Alzheimer's. High levels could be a sign of many different neurological diseases and injuries."

The test detects neurofilament light chain, a structural protein which forms part of the internal skeleton of neurons. When neurons are damaged or dying, the protein leaks out into the cerebrospinal fluid that bathes the brain and spinal cord and from there, into the bloodstream.

Finding high levels of the protein in a person's cerebrospinal fluid provides strong evidence that some of their brain cells have been damaged. But obtaining cerebrospinal fluid requires a spinal tap, which many people are reluctant to undergo. Senior author Mathias Jucker, a professor of cellular neurology at the German Centre for Neurodegenerative Diseases in Tübingen, along with Gordon and colleagues from all over the world, studied whether levels of the protein in blood also indicate neurological damage.

Researchers turned to a group of families with rare genetic variants that cause Alzheimer's at a young age - typically in a person's 50s, 40s or even 30s. The families form the study population of the Dominantly Inherited Alzheimer's Network (DIAN), an international consortium led by Washington University that investigates the roots of Alzheimer's disease. A parent with this mutation has a 50% of passing the genetic error to a child, and any child who inherits a variant is highly likely to develop symptoms of dementia near the same age as his or her parent. This timeline gives researchers an opportunity to study what happens in the brain in the years before cognitive symptoms arise.

In those with the faulty gene variant, protein levels were higher at baseline and rose over time. In contrast, protein levels were low and largely steady in people with the healthy form of the gene. This difference was detectable 16 years before cognitive symptoms were expected to arise.



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