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Protein Changes Detected in Blood Years Before Alzheimer’s Onset

The observation could pave the way for a blood test to predict disease progression in people with a genetic predisposition to developing the neurodegenerative disorder.

Jan 21, 2019
Jef Akst

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Levels of a protein called neurofilament light chain increase in the blood and spinal fluid of some Alzheimer’s patients 16 years before they develop symptoms, according to a study published today (January 21) in Nature Medicine.

The results suggest that neurofilament light chain (NfL), which is part of the cytoskeleton of neurons and has previously been tied to brain damage in mice, could serve as a biomarker to noninvasively track the progression of the disease. “This is something that would be easy to incorporate into a screening test in a neurology clinic,” coauthor Brian Gordon, an assistant professor of radiology at Washington University, says in a press release.  

See “Researchers Develop Potential Blood Test for Alzheimer’s Disease

Gordon and his colleagues measured NfL in nearly 250 people carrying an Alzheimer’s-risk allele and more than 160 of their relatives who did not carry the variant. They found that those at risk of developing the disease had higher levels of the protein early on, and that NfL levels in both the blood and spinal fluid were on the rise well before the patients began to show signs of neurodegeneration, more than 16 years before disease onset.

Examining a subset of the patients more closely, the team saw that the rate of increase in NfL correlated with the shrinkage of a brain region called the precuneus, and patients whose NfL levels were rising rapidly tested worse on cognitive tests. “It is not necessarily the absolute levels which tell you your neurodegeneration is ongoing, it is the rate of change,” coauthor Mathias Jucker, a professor of cellular neurology at the German Center for Neurodegenerative Diseases in Tübingen, tells The Guardian.

The Alzheimer’s-linked mutation carried by patients examined in this study only affects about 1 percent of people who get the neurodegenerative disease, so the approach must be validated in a broader patient population, James Pickett, the head of research at the Alzheimer’s Society, tells The Guardian.

“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,” Gordon says in the release. “I could see this being used in the clinic in a few years to identify signs of brain damage in individual patients.”

Meanwhile, a research team at Seoul National University in South Korea described another potential blood test for Alzheimer’s, focusing on the tau and amyloid proteins known to be associated with the disease. According to their study published today in Brain, blood levels of tau and amyloid correlate with how much tau has accumulated in the brain, as well as other markers of neurodegeneration such as hippocampal volume. “These results indicate that combination of plasma tau and amyloid-β1–42 levels might be potential biomarkers for predicting brain tau pathology and neurodegeneration,” the researchers write in their report.

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