Blood test may give early Alzheimer’s diagnosis

A simple blood test could detect the early danger signs of Alzheimer’s disease long before confusion and memory loss set in, a new study suggests.

Researchers from Europe, the US and Australia, led by the German Centre for Neurodegenerative Diseases (DZNE) in Tübingen, have discovered a link between neurofilament light chain, a structural protein that forms part of the internal skeleton of neurons, and the later onset of the disease. 

Writing in a paper published in Nature Medicine, they report using blood tests to detect the levels of the neurofilament light chain, allowing them to predict the development of Alzheimer’s more than a decade before patients began to show cognitive impairments.

Long before outward symptoms of Alzheimer’s disease develop, the brain starts changing and neurons slowly degrade. When those neurons are damaged or dying, proteins leak out into the cerebrospinal fluid that surrounds the brain, and from there into the bloodstream.

“Normally such proteins are rapidly degraded in the blood and are therefore not very suitable as markers for a neurodegenerative disease,” says DZNE’s Mathias Jucker, who led the research.

“An exception, however, is a small piece of so-called neurofilament that is surprisingly resistant to this degradation.”

The researchers studied more than 400 people participating in the Dominantly Inherited Alzheimer’s Network (DIAN) study, a group of families with genetic variations that lead to Alzheimer’s in middle age. 

Of the participants used to develop the blood test, 247 carried an early-onset genetic variant, and were compared with 162 of their unaffected relatives. The genetic variation all but guarantees the carrier will develop symptoms of dementia.

Those carrying the faulty gene variant had neurofilament light chain protein levels which 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.

The rising levels of neurofilament light chain in the blood were also confirmed to predict cognitive decline. Thirty-nine of the patients revisited the clinic around two years after their last visit, and underwent brain scans and two cognitive tests. 

Those whose blood protein levels had risen rapidly were most likely to show signs of brain degeneration and diminished cognitive abilities on their second visit.

“It is not the absolute neurofilament concentration, but its temporal evolution, which is meaningful and allows predictions about the future progression of the disease,” says Jucker.

“We were able to predict loss of brain mass and cognitive changes that actually occurred two years later.”

Those changes in the blood became noticeable up to 16 years before the calculated onset of dementia symptoms.

It is hoped, however, that the test could help diagnose those at risk of a range of neurodegenerative conditions. 

“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,” says Brian Gordon from Washington University in St. Louis, US, who also worked on the research.

While a commercial kit is available to test for protein levels in the blood, it has not been approved for use to diagnose or predict an individual’s risk of brain damage. 

Before that approval can be given, the researchers will need to establish the clinical relevance of protein levels in the blood – essentially, how much protein is too much. 

Another question also remains around the rate of change of protein levels, and how quickly protein levels can rise before it becomes a cause for concern.