4 Hopeful Approaches to the Future of Alzheimer's Treatment


Anyone who has watched the slow unraveling of the mind of a loved one to Alzheimer’s disease knows how crucial it is to develop new treatments. In America alone, currently more than 5.3 million people are living with Alzheimer’s and 15 million are providing care for loved ones with the disease. Unless treatments are developed to slow or even cure it, 28 million baby boomers will fall ill with Alzheimer's by 2040, consuming 24 percent of Medicare spending, according to a report from the 2015 Alzheimer’s Association International Conference (AAIC).

Alzheimer’s, an aggressive form of age-related dementia (of which there are several forms), is a result of accumulations and “misfolding” of proteins in the brain known as amyloid fibrils and tau tangles. In large amounts, these proteins are toxic to brain cells and cause degeneration.

But there is hope on the horizon for earlier detection due to new research, and new studies into treatments that may eventually lead to drugs and, possibly, a cure. Since Alzheimer’s is generally considered an elderly person’s disease, very early onset Alzheimer’s—which can begin as early as age 50—often goes undetected until it’s far too late for significant symptom treatment. That's why earlier detection is such a focus of research. 

1. Testing Saliva May Allow for Earlier Detection

Alzheimer’s researchers are excited about the potential of a new saliva test, the work of a neuroscience graduate student at the University of Alberta, Canada named Shradda Sapkota, who presented her research at the AAIC in July. Using a form of protein analysis called liquid chromatography-mass spectrometry (LCMS), researchers analyzed saliva samples to determine which substances were predominant in the saliva of Alzheimer’s patients, and considered this in conjunction with cognitive information on the patients. The results suggest that higher levels of certain substances are present in the blood of Alzheimer’s patients and predicted “worse episodic memory performance” and “slower speed in processing information.

Currently, no known blood or saliva test exists, though research has and continues to be done on potential blood-based biomarkers and a saliva test that could be used for early detection. “This is the first we’ve seen a potential saliva test presented,” Heather Snyder, director of medical and scientific operations at the Alzheimer’s Association, tells mental_floss. While it’s still in the very early days, we are going to need this tool, and it may be a low-cost way to look at who will need more aggressive screening and treatment.”

2. Sampling Cerebrospinal Fluid: the Canary in the Coal Mine

The cerebrospinal fluid (CSF) that offers protection to the brain and spinal cord might also contain a key biomarker of Alzheimer’s. When the brain experiences injury or toxicity, certain proteins are released into the CSF. One such protein, neurogranin—which is found only in the brain—has turned up in significantly higher amounts in the CSF of Alzheimer’s patients, suggesting it may be a powerful marker for diagnosis and prognosis of Alzheimer’s. However, this is a more invasive form of obtaining diagnosis, usually reserved for those who are younger or in what is known as “mild cognitive impairment” stage, where they still have relatively good memory and functioning.

The earlier Alzheimer’s is caught, the better the effectiveness of existing medications like Aricept. These medications don’t slow the disease or cure it but, says Snyder, “they turn up the volume so the brain cells that are still there can talk to one another longer—like a hearing aid.”

3. Imaging Inflammation: PET Scans Offer Noninvasive Diagnostics

PET scan technology, an imaging technique in which a radioactive tracer is used to look for disease in the body, has made it possible to isolate out tau tangles in the brain, which—along with amyloid plaques—are a key marker of Alzheimer’s. The presence of tau tangles helps to understand how advanced a person’s disease may be. PET scan imaging is also a relatively noninvasive detection method that may help with earlier diagnosis. “We’ve seen real development of this technology,” Snyder says. “It gives us the ability to look at the change and build-up of proteins over time in the brain.” The imaging can also be used to track inflammation, whose role in Alzheimer’s is still being investigated. PET scans can also monitor microglial cells, the brain’s immune cells, by tracking a protein that turns up when these healthy cells are destroyed and give a better picture of brain health.

4. An Inhibitor Molecule Breaks the Cycle

Of the breakthroughs that hold the most promise for a cure, inhibitor molecules, which bind to enzymes and proteins and help keep their homeostasis, show potential to stop formation of the amyloid proteins that build up in Alzheimer’s disease. One such molecule, known as Brichos,” which is technically a “chaperone” molecule—a type of molecule that helps proteins in the brain to form properly—has the ability to stick to misbehaving amyloid fibrils that cause brain degeneration, according to a study published in the journal Nature Structural & Molecular Biology.

These inhibitors may be able to interrupt the key phase where amyloid fibrils become toxic clusters, the hallmark of Alzheimer’s disease, but also a key in diseases like Parkinson’s. Inhibiting amyloid fibrils is the most critical stage in prevention of Alzheimer’s because once amyloid proteins misfold, they can create a chain reaction where other proteins follow suit—known as oligomers, creating swifter toxicity and degeneration of brain neurons. Although the studies were done on mice, this discovery is a promising area of research for treatments, and maybe even a cure. Preliminary research is promising, though it is still in the early stages of study.

Editor's note: this post has been updated.

Why Is Your First Instinct After Hurting Your Finger to Put It in Your Mouth?

If you close your fingers in a car door or slam your funny bone into a wall, you might find your first reaction is to suck on your fingers or rub your elbow. Not only is this an instinctive self-soothing behavior, it's a pretty effective technique for temporarily calming pain signals to the brain.

But how and why does it work? To understand, you need to know about the dominant theory of how pain is communicated in the body.

In the 17th century, French scientist and philosopher René Descartes proposed that there were specific pain receptors in the body that "rang a bell in the brain" when a stimulus interacted with the body, Lorne Mendell, a professor of neurobiology and behavior at Stony Brook University in New York, tells Mental Floss. However, no study has effectively been able to identify receptors anywhere in the body that only respond to painful stimuli.

"You can activate certain nerve fibers that can lead to pain, but under other circumstances, they don't," Mendell says. In other words, the same nerve fibers that carry pain signals also carry other sensations.

In 1965, two researchers at MIT, Patrick Wall and Ronald Melzack, proposed what they called the gate control theory of pain, which, for the most part, holds up to this day. Mendell, whose research focuses on the neurobiology of pain and who worked with both men on their pain studies, explains that their research showed that feeling pain is more about a balance of stimuli on the different types of nerve fibers.

"The idea was that certain fibers that increased the input were ones that opened the gate, and the ones that reduced the input closed the gate," Mendell says. "So you have this idea of a gate control sitting across the entrance of the spinal cord, and that could either be open and produce pain, or the gate could be shut and reduce pain."

The gate control theory was fleshed out in 1996 when neurophysiologist Edward Perl discovered that cells contain nociceptors, which are neurons that signal the presence of tissue-damaging stimuli or the existence of tissue damage.

Of the two main types of nerve fibers—large and small—the large fibers carry non-nociceptive information (no pain), while small fibers transmit nociceptive information (pain).

Mendell explains that in studies where electric stimulation is applied to nerves, as the current is raised, the first fibers to be stimulated are the largest ones. As the intensity of the stimulus increases, smaller and smaller fibers get recruited in. "When you do this in a patient at low intensity, the patient will recognize the stimulus, but it will not be painful," he says. "But when you increase the intensity of the stimulus, eventually you reach threshold where suddenly the patient will say, 'This is painful.'"

Thus, "the idea was that shutting the gate was something that the large fibers produced, and opening the gate was something that the small fibers produced."

Now back to your pain. When you suck on a jammed finger or rub a banged shin, you're stimulating the large fibers with "counter irritation," Mendell says. The effect is "a decrease in the message, or the magnitude of the barrage of signals being driven across the incoming fiber activation. You basically shut the gate. That is what reduces pain."

This concept has created "a big industry" around treating pain with mild electrical stimulation, Mendell says, with the goal of stimulating those large fibers in the hopes they will shut the gate on the pain signals from the small fibers.

While counter irritation may not help dull the pain of serious injury, it may come in handy the next time you experience a bad bruise or a stubbed toe.

Jamie McCarthy/Getty Images for Bill & Melinda Gates Foundation
Bill Gates is Spending $100 Million to Find a Cure for Alzheimer's
Jamie McCarthy/Getty Images for Bill & Melinda Gates Foundation
Jamie McCarthy/Getty Images for Bill & Melinda Gates Foundation

Not everyone who's blessed with a long life will remember it. Individuals who live into their mid-80s have a nearly 50 percent chance of developing Alzheimer's, and scientists still haven't discovered any groundbreaking treatments for the neurodegenerative disease [PDF]. To pave the way for a cure, Microsoft co-founder and philanthropist Bill Gates has announced that he's donating $100 million to dementia research, according to Newsweek.

On his blog, Gates explained that Alzheimer's disease places a financial burden on both families and healthcare systems alike. "This is something that governments all over the world need to be thinking about," he wrote, "including in low- and middle-income countries where life expectancies are catching up to the global average and the number of people with dementia is on the rise."

Gates's interest in Alzheimer's is both pragmatic and personal. "This is something I know a lot about, because men in my family have suffered from Alzheimer’s," he said. "I know how awful it is to watch people you love struggle as the disease robs them of their mental capacity, and there is nothing you can do about it. It feels a lot like you're experiencing a gradual death of the person that you knew."

Experts still haven't figured out quite what causes Alzheimer's, how it progresses, and why certain people are more prone to it than others. Gates believes that important breakthroughs will occur if scientists can understand the condition's etiology (or cause), create better drugs, develop techniques for early detection and diagnosis, and make it easier for patients to enroll in clinical trials, he said.

Gates plans to donate $50 million to the Dementia Discovery Fund, a venture capital fund that supports Alzheimer's research and treatment developments. The rest will go to research startups, Reuters reports.

[h/t Newsweek]


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