Antibody Makes Alzheimer’s Protein Detectable in Blood

Antibodies to Tau

Caption: The protein tau (green) aggregates abnormally in a brain cell (blue). Tau spills out of the cell and enters the bloodstream (red). Research shows that antibodies (blue) can capture tau in the blood that reflect its levels in the  brain.
Credit: Sara Moser

Age can bring moments of forgetfulness. It can also bring concern that the forgetfulness might be a sign of early Alzheimer’s disease. For those who decide to have it checked out, doctors are likely to administer brief memory exams to assess the situation, and medical tests to search for causes of memory loss. Brain imaging and spinal taps can also help to look for signs of the disease. But an absolutely definitive diagnosis of Alzheimer’s disease is only possible today by examining a person’s brain postmortem. A need exists for a simple, less-invasive test to diagnose Alzheimer’s disease and similar neurodegenerative conditions in living people, perhaps even before memory loss becomes obvious.

One answer may lie in a protein called tau, which accumulates in abnormal tangles in the brains of people with Alzheimer’s disease and other “tauopathy” disorders. In recent years, researchers have been busy designing an antibody to target tau in hopes that this immunotherapy approach might slow or even reverse Alzheimer’s devastating symptoms, with promising early results in mice [1, 2]. Now, an NIH-funded research team that developed one such antibody have found it might also open the door to a simple blood test [3].

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A New Tool in the Toolbox: New Method Traces Free-Floating DNA Back to Its Source

Graphic

Caption: DNA (blue) loops around nucleosomes (gray) and is bound by transcription factors (red), proteins that switch genes on and off and act in a tissue-specific manner. When cells die, enzymes (scissors) chop up areas between the nucleosomes and transcription factors, releasing DNA fragments in unique patterns. By gathering the released DNA fragments in blood, researchers can tell which types of cells produced them.
Credit: Shendure Lab/University of Washington

When cells die, scissor-like enzymes snip their DNA into tiny fragments that leak into the bloodstream and other bodily fluids. Researchers have been busy in recent years working on ways to collect these free-floating bits of DNA and explore their potential use in clinical care.

These approaches, sometimes referred to as “liquid biopsies,” hinge on the ability to distinguish specific DNA fragments from the body’s normal background of “cell-free” DNA, most of which comes from dying white blood cells. Seeking other sources for cell-free DNA in particular situations is beginning to bear fruit, however. Current applications include: 1) a test in maternal blood to look for DNA from the fetus (actually from the fetal component of the placenta), which provides a means of detecting a possible genetic abnormality; 2) a test in a cancer patient’s blood to look for cancer-specific mutations, as a way of assessing response to treatment or early signs of relapse; and 3) a test in an organ transplant recipient, where increasing abundance of DNA fragments from the donor can be an early sign of rejection.

But recent proposals have been floated about looking for cell-free DNA in healthy individuals, as an early sign of some health problems. Suppose something was found—how could you know the source? Now a team of NIH-funded researchers has devised a new method that uses distinctive features of DNA packaging to provide an additional layer of information about the origins of free-floating DNA, vastly expanding the potential uses for such tests [1].

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Gene Expression Test Aims to Reduce Antibiotic Overuse

Doctor with ER patient

Caption: Duke physician-scientist Ephraim Tsalik assesses a patient for a respiratory infection.
Credit: Shawn Rocco/Duke Health

Without doubt, antibiotic drugs have saved hundreds of millions of lives from bacterial infections that would have otherwise been fatal. But their inappropriate use has led to the rise of antibiotic-resistant superbugs, which now infect at least 2 million Americans every year and are responsible for thousands of deaths [1]. I’ve just come from the World Economic Forum in Davos, Switzerland, where concerns about antibiotic resistance and overuse was a topic of conversation. In fact, some of the world’s biggest pharmaceutical companies issued a joint declaration at the forum, calling on governments and industry to work together to combat this growing public health threat [2].

Many people who go to the doctor suffering from respiratory symptoms expect to be given a prescription for antibiotics. Not only do such antibiotics often fail to help, they serve to fuel the development of antibiotic-resistant superbugs [3]. That’s because antibiotics are only useful in treating respiratory illnesses caused by bacteria, and have no impact on those caused by viruses (which are frequent in the wintertime). So, I’m pleased to report that a research team, partially supported by NIH, recently made progress toward a simple blood test that analyzes patterns of gene expression to determine if a patient’s respiratory symptoms likely stem from a bacterial infection, viral infection, or no infection at all.

In contrast to standard tests that look for signs of a specific infectious agent—respiratory syncytial virus (RSV) or the influenza virus, for instance—the new strategy casts a wide net that takes into account changes in the patterns of gene expression in the bloodstream, which differ depending on whether a person is fighting off a bacterial or a viral infection. As reported in Science Translational Medicine [4], Geoffrey Ginsburg, Christopher Woods, and Ephraim Tsalik of Duke University’s Center for Applied Genomics and Precision Medicine, Durham, NC, and their colleagues collected blood samples from 273 people who came to the emergency room (ER) with signs of acute respiratory illness. Standard diagnostic tests showed that 70 patients arrived in the ER with bacterial infections and 115 were battling viruses. Another 88 patients had no signs of infection, with symptoms traced instead to other health conditions.

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Snapping Together a New Microlab

Microlabs

Credit:  Viterbi School of Engineering, University of Southern California

Just as the computational power of yesterday’s desktop computer has been miniaturized to fit inside your mobile phone, bioengineers have shrunk traditional laboratory instruments to the size of a dime. To assemble a “snap lab” like the one you see above, all scientists have to do is click together some plastic components in much the same way that kids snap together the plastic bricks in their toy building sets.

The snap lab, developed by an NIH-funded team led by Noah Malmstadt at the University of Southern California (USC) Viterbi School of Engineering, Los Angeles, is an exciting example of a microfluidic circuit—tiny devices designed  to test just a single drop of blood, saliva, or other fluids. Such devices have the potential to make DNA analysis, microbe detection, and other biomedical tests easier and cheaper to perform.

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