In a new study, researchers from Boston University School of Medicine (BUSM) describe a unique model for the biology of Alzheimer’s disease (AD) which may lead to an entirely novel approach for treating the disease. The findings appear in the journal Nature Neuroscience.
AD is a major cause of disease in the elderly and places a huge financial cost on the health care system. Scientists have known for a long time that two proteins (beta-amyloid and tau) clump and accumulate in the brains of Alzheimer patients, and this accumulation is thought to cause nerve cell injury that results in dementia.
Recent work by these BUSM researchers has shown that the clumping and accumulation of tau occurs as a normal response to stress, producing RNA/protein complexes termed “stress granules,” which reflect the need for the brain to produce protective proteins. The persistence of this “stress response” leads to excessive stress, the accumulation of pathological stress granules, and the accumulation of clumped tau, which drives nerve cell injury and produces dementia.
In the current study, the researchers use this new model and show that reducing the level of stress granule proteins yields strong protection, possibly by reducing persistent pathological stress granules as well as changing the type of tau clumping that occurs.
The team hypothesized that they could delay the disease process by reducing stress granules and decreasing this persistent stress response by genetically decreasing TIA1, which is a protein that is required for stress granule formation. Reducing TIA1 improved nerve cell health and produced striking improvements in memory and life expectancy in an experimental model of AD.
Hacking the human body is all the rage these days. A few years back, scientists made waves by developing a technique (dubbed CRISPR) that literally cuts DNA at specific locations to edit out the genes that lead to disease. The implications for this are as enormous as they are diverse. However, the approach is far from perfect. And you’d really rather not have any errors when messing with something as permanent as the human genome.
So researchers have been working on a way to make gene editing safer. One approach, described this week in the journal Science, works by editing the far less permanent component of gene creation, RNA. Scientists think that this new tool could be safer than slicing and dicing DNA itself.
A quick refresher on CRISPR and gene editing
CRISPR stands for clustered regularly interspaced short palindromic repeats. They are small pieces of bacterial DNA that contain genetic information identical to that found in viruses. Along with enzymes called Cas, they are part of many microbial immune systems. When viruses attempt to invade, the bacteria recognize them (from CRISPR copy cats) and cut them with the Cas enzymes, preventing them from reproducing any further.
In Canada, many kids are on ice skates before they can walk. But they don’t get to start slamming into each other until they’re around 11, when they can sign up for full contact hockey. Unsurprisingly, that’s also the age when the baby Wayne Gretzky’s start getting their first concussions.
If they take a knock, the puck-hungry preteens are sidelined until they pass through a standard return-to-play protocol: after the initial symptoms subside, the recommended approach is for athletes to gradually ramp up activity, making sure headaches and dizziness don’t return at each step of the way. Once they pass through that incremental increase without issue, doctors will clear them to return to the rink.
But a new study shows that even when young hockey players who suffer concussions appear fully recovered, and doctors and trainers return them to the ice, scans still show abnormalities in the brain. The findings were published today in the journal Neurology, and add to a growing number of studies showing that neurological changes linger even after clinical symptoms of a concussion clear up. Athletes may appear back to normal on a battery of cognitive and physical tests, but not on an MRI scan.
“The problem is those tests don't seem to be very sensitive in the long run,” says study author Ravi Menon, director of the Centre for Functional and Metabolic Mapping at Western’s Robarts Research Institute in Ontario. “They return to normal quickly, but the MRI data shows the brain is still healing.”
Menon’s study followed a group of male hockey players, aged 11 to 14. Fourteen players suffered a concussion during the season, and went through a functional MRI scan, cognitive, memory and balance test both one to three days after the injury and again three months later. Their tests were compared with those of 26 injury-free players, who served as controls.
A sort of self-satisfied rage sets in whenever I see someone struggling to navigate typical life—and inconveniencing me in the process—because they simply cannot look up from their phone. I recently found myself stuck behind a woman gamely attempting to maneuver through a narrow bus aisle while keeping her gaze firmly attached to her screen. When she almost tripped over a broad step (which, in addition to slip-resistant traction, sported a wide, bright yellow streak designed to make the stair highly visible—no match for the glare of a smartphone, apparently) I had to hold back a snicker. I don’t think Manoush Zomorodi, the author of the recent book Bored and Brilliant: Rediscovering the Lost Art of Spacing Out, intended for the text to turn me into such a jerk. That’s just a side benefit.
In the book, which is an outgrowth of her WNYC podcast Note to Self, Zomorodi’s isn’t trying to turn readers into smug luddites who only own flip phones. Instead, the book’s seven challenges (one for each day in a week) are designed to help readers reclaim their time from digital distractions—without giving up smartphone usage—and to give them the mental space to be bored. Bored? Yes, bored.