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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Snapshots of Life: Neurons in a New Light

Mouse Midbrain

Credit: Michael Shribak, Marine Biological Laboratory, Woods Hole, MA

Birds do it, bees do it, and even educated fleas do it. No, not fall in love, as the late Ella Fitzgerald so famously sang. Birds and insects can see polarized light—that is, light waves transmitted in a single directional plane—in ways that provides them with a far more colorful and detailed view of the world than is possible with the human eye.

Still, thanks to innovations in microscope technology, scientists have been able to tap into the power of polarized light vision to explore the inner workings of many complex biological systems, including the brain. In this image, researchers used a recently developed polarized light microscope to trace the spatial orientation of neurons in a thin section of the mouse midbrain. Neurons that stretch horizontally appear green, while those oriented at a 45-degree angle are pinkish-red and those at 225 degrees are purplish-blue. What’s amazing is that these colors don’t involve staining or tagging the cells with fluorescent markers: the colors are generated strictly from the light interacting with the physical orientation of each neuron.

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Aging Research: Plasma Protein Revitalizes the Brain

Elixir of youth?For centuries, people have yearned for an elixir capable of restoring youth to their aging bodies and minds. It sounds like pure fantasy, but, in recent years, researchers have shown that the blood of young mice can exert a regenerative effect when transfused into older animals. Now, one of the NIH-funded teams that brought us those exciting findings has taken an early step toward extending them to humans.

In their latest work published in Nature, the researchers showed that blood plasma collected from the umbilical cords of newborn infants possesses some impressive rejuvenating effects [1]. When the human plasma was infused into the bloodstream of old mice, it produced marked improvements in learning and memory. Additional experiments traced many of those cognitive benefits to a specific protein called TIMP2—an unexpected discovery that could pave the way for the development of brain-boosting drugs to slow the effects of aging.

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Exercise Releases Brain-Healthy Protein

ExerciseWe all know that exercise is important for a strong and healthy body. Less appreciated is that exercise seems also to be important for a strong and healthy mind, boosting memory and learning, while possibly delaying age-related cognitive decline [1]. How is this so? Researchers have assembled a growing body of evidence that suggests skeletal muscle cells secrete proteins and other factors into the blood during exercise that have a regenerative effect on the brain.

Now, an NIH-supported study has identified a new biochemical candidate to help explore the muscle-brain connection: a protein secreted by skeletal muscle cells called cathepsin B. The study found that levels of this protein rise in the blood of people who exercise regularly, in this case running on a treadmill. In mice, brain cells treated with the protein also exhibited molecular changes associated with the production of new neurons. Interestingly, the researchers found that the memory boost normally provided by exercise is diminished in mice unable to produce cathepsin B.

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Creative Minds: A New Chemistry for Aging Research?

Tony Wyss-Coray

Tony Wyss-Coray / Credit: Stanford School of Medicine

Basic scientists have long studied aging by looking inside of cells. While this research has produced many important leads, they are now starting to look outside the cell for the wealth of biochemical clues contained in the bloodstream.

To introduce you to this exciting frontier in aging research, this blog highlighted a while back the work of Tony Wyss-Coray at Stanford School of Medicine, Palo Alto, CA. He and a colleague had just received a 2013 NIH Director’s Transformative Research Award to explore the effects of exercise on the brains of mice. Their work, in fact, produced one of Science Magazine’s Breakthrough Discoveries of 2014. Their team showed that by fusing the circulatory systems of old and young mice to create a shared blood supply, the young blood triggered new muscle and neural connections in the older mice, while also improving their memories.

As fascinating as this theoretical Fountain of Youth was, Wyss-Coray recognized a critical limitation. He had no way of knowing how factors secreted by the young mouse could actually cross the blood-brain barrier and rejuvenate neurons. To solve this unknown, Wyss-Coray recently received a 2015 NIH Director’s Pioneer Award to build a potentially game-changing tool to track the aging process in mice.

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