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Blood test detects Alzheimer's years before symptoms

Changes in levels of a protein might reveal onset of disease more than 10 years before symptoms appear

Ingrid Torjesen

Wednesday, 23 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, according to a study* published in Nature Medicine.

The test detects neurofilament light chain, a structural protein that forms part of the internal skeleton of neurons. When brain 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 has been shown to provide 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.

US and German researchers studied whether levels of the protein in blood also reflect neurological damage. They accessed data on families with rare genetic variants that cause Alzheimer's at a young age - typically in a person's 50s, 40s or even 30s - who form part of the Dominantly Inherited Alzheimer's Network (DIAN). A parent with such a mutation has a 50% chance of passing the genetic error to a child, and any child who inherits a variant is all but guaranteed to develop symptoms of dementia near the same age as his or her parent.

The researchers studied more than 400 people participating in the DIAN study, 247 who carry an early-onset genetic variant and 162 of their unaffected relatives. Each participant had previously visited a DIAN clinic to give blood, undergo brain scans and complete cognitive tests. Roughly half had been evaluated more than once, typically about two to three years apart.

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.

To find out whether protein blood levels could be used to predict cognitive decline, the researchers collected data on 39 people with disease-causing variants when they returned to the clinic an average of two years after their last visit. The participants underwent brain scans and two cognitive tests: the Mini-Mental State Exam and the Logical Memory test. The researchers found that people whose blood protein levels had previously risen rapidly were most likely to show signs of brain atrophy and diminished cognitive abilities when they revisited the clinic.

Mathias Jucker, a professor of cellular neurology at the German Center for Neurodegenerative Diseases in Tübingen, said "It will be important to confirm our findings in late-onset Alzheimer´s disease and to define the time period over which neurofilament changes have to be assessed for optimal clinical predictability."

All kinds of neurological damage can cause the neurofilament light protein to spill out of neurons and into blood. Protein levels are high in people with Lewy body dementia and Huntington's disease; they rise dramatically in people with multiple sclerosis during a flare-up and in football players immediately after a blow to the head.

As a result, the researchers said the technique could be applied to quickly and inexpensively identify brain damage in people with not just Alzheimer's disease but 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."


*Preische O, Schultz SA, Apel A, et al. Serum neurofilament dynamics predicts neurodegeneration and clinical progression in presymptomatic Alzheimer’s disease. Nature Medicine (2019), 21 January 2019, doi: 10.1038/s41591-018-0304-3

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