Monthly Archives: November 2016

Breakthrough in Alzheimer’s Research: What We Thought About Tau Tangles May Be All Wrong

The main hallmark of Alzheimer’s disease is the accumulation of toxic protein species in the brain. These toxic deposits include senile plaques (made of the amyloid-beta protein) and neurofibrillary tangles (made of the tau protein). In general, recent drug development research for Alzheimer’s has focused on targeting amyloid-beta. This is because previous research suggested that amyloid-beta is responsible for initiating a set of chemical reactions that lead to the phosphorylation of tau. This p-tau (phosphorylated tau) is then more prone to sticking to itself and forming tangles. Thus, the thinking was that if we could get rid of amyloid-beta, tau would no longer form tangles, allowing us to eliminate both toxic proteins at once.


Plaques and tangles in a normal and Alzheimer’s disease brain.

However, a study published this week in the journal Science may completely change how we think about amyloid-beta and tau. Researchers from Australia looked at enzymes of the p35 family, which are believed to mediate amyloid-beta’s ability to initiate p-tau formation. They focused on a member of this protein family called p35-delta (p35D), after determining that it was the only p35 protein that localized to synapses (the communication junctions between neurons.)

The exciting part of this study came when the researchers generated Alzheimer’s mice that lacked the gene for p35D. These mice experienced exacerbated symptoms of Alzheimer’s disease, including worsened excitotoxicity, memory loss, and premature death. The researchers determined experimentally that these worsened symptoms were dependent on p35D’s ability to create p-tau. In other words, it seems that the presence of p35D (and in turn, the presence of p-tau) was actually protecting the mice from more severe symptoms of Alzheimer’s disease.

This study is big news in the field of neuroscience because it suggests that the formation of tangles by the p-tau protein may be helpful rather than harmful. Whereas in the past scientists have viewed tangles as a harmful side effect of amyloid-beta plaques, these new results indicate that p-tau may actually be a beneficial reaction to the plaques which keeps their toxicity in check. This is consistent with additional data from the study showing that humans with Alzheimer’s disease have reduced expression of p35D. The authors of the paper suggested that a decline in p35D expression, and in turn a decline in p-tau levels, may be a major contributor to the development of Alzheimer’s disease.

Alzheimer’s researchers around the world are very excited about this paper and the ramifications it could have for future studies. Where previously we had been trying to deplete toxic p-tau, this strategy may actually worsen the disease. Rather, perhaps we should be trying to increase levels of p35D and/or p-tau in early Alzheimer’s patients in order to prevent disease progression. It’s possible that this study may also help explain why approximately 1 in 5 elderly adults contain the signature pathology of Alzheimer’s in their brains and yet do not experience any cognitive deficits. Perhaps these individuals benefit from higher expression of p35D which helps fight of the toxicity of amyloid-beta. Future studies will investigate whether this is indeed the case.

As always, we must interpret these results with caution. Since this study was based in mice, a lot of additional research will be needed to determine whether similar neurochemical pathways occur in humans and, if so, whether these can be utilized to design a preventative treatment for Alzheimer’s. Only time can tell how far-reaching the impacts of this study will be.


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Do Brain-Training Games Really Prevent Alzheimer’s?

In January 2016, Luminosity was forced to pay $2 million dollars after being sued for false advertising. Ads for the popular “brain-training” game suggested that the mental exercises could improve cognition and even reduce the effects of dementia. However, these claims have not stood up to scientific examination. In this article I’ll break down the science of neuroplasticity that brain-training games are based on, review the evidence of their inefficacy, and finally provide a few scientifically valid alternatives to brain games.

The Plastic Brain

What exactly is the “science of neuroplasticity” that ads for Lumunosity and other brain-training games keep talking about? In this context, plastic means changeable. Thus, the field of neuroplasticity examines the ways our brains can change over time. For much of the history of neuroscience, it was believed that only infants and children had plastic brains. The popular theory was that children’s brains were in a critical period of rapid change that allowed them to quickly learn new things such as language. This critical period was thought to end around the age of five, at which point our brain structure would remain static for the rest of our lives.

However, within the past few decades, evidence has emerged to suggest that the adult brain is also plastic, albeit to a lesser extent than children’s brains. You may have heard stories of blind people who possess a seemingly-superhuman sense of hearing. These are more than just anecdotes. Multiple studies have demonstrated this phenomenon to be true, even when vision loss occurs during adulthood. The brain space that had once been devoted to vision is taken over by the other senses. Similarly, many adults are able to partially recover from neurological injuries such as a stroke or traumatic brain injury by utilizing their brains’ capacity for change, creating new neural connections to make up for those that were damaged.

A simple dogma has emerged from studies of adult neuroplasticity: “neurons that fire together, wire together.” This basically means that the more a particular neural circuit is activated, the stronger the connections between those neurons become. It’s kind of as if your brain were a muscle, and activating neural pathways were like a “workout” for your brain. This is a bit of an oversimplification, but it illustrates the fact that we tend to become better at cognitive tasks the more we practice them. These improvements correspond to physical changes that occur inside our brains, just like a muscle growing larger and stronger.

This is the basis for brain-training games like Luminosity. Based on what we currently know about neuroplasticity, it makes sense that playing games that involve memory, logic, or problem-solving should improve the relevant neural circuits and result in better cognitive function overall. So then, what’s the problem?

Why Brain-Training Games Don’t Work

Let’s say you’re playing a card-matching game that’s designed to improve memory. Each game is randomly-generated so the cards are never in the same spots each time. The first time you play, it might take you five minutes to complete the puzzle. The next time, you’re a little faster. You play this game every day for a month. By the end of the month, you can complete the task in half your original time. It’s reasonable to think that your memory is now far better compared to when you first played the game.

However, just because you’re better at this particular game doesn’t mean that your overall memory has improved. To date there has been little evidence that playing these games can improve practical memory skills such as remembering where you left your keys or recalling a friend’s phone number. In fact, cognitive improvements due to brain-training games are often very narrow in scope, only applying tasks that are very similar to the game itself. Additionally, while some studies have suggested that these gains are lasting, others report that the effects of brain training dissipate over time. Most importantly, there has been zero evidence to suggest that these games can reduce the risk or symptoms of Alzheimer’s or other dementias.

The problems with brain-training games were highlighted in a consensus report published in 2014. The report was signed by 70 experts in cognitive science, neuroscience, and gerontology. It argued that advertisements promising broad cognitive enhancement by brain-training games were highly exaggerated and lacked solid scientific support.

So, Now What?

You might be thinking: okay, maybe these games aren’t the magic dementia cure they claim to be, but surely there’s no harm in playing them? After all, it’s likely that these games do produce some small improvement to cognitive function, albeit narrow and probably temporary. But if there’s even a small chance of making our brains healthier, shouldn’t we take it?

The question here isn’t whether brain-training games produce any beneficial effects, but whether the beneficial outweigh the opportunity cost. This was a key point of the consensus report that I mentioned earlier:

“Time spent playing the games is time not spent reading, socializing, gardening, exercising, or engaging in many other activities that may benefit cognitive and physical health of older adults.”

So it’s not that brain-training games do nothing for cognition, but that their effects are minuscule compared to other scientifically-validated approaches for reducing the risk of dementia. These include incorporating more fruits and vegetables into your diet, maintaining an active social life, and keeping your mind active through a variety of intellectually stimulating tasks. Check out the Alzheimer’s Association’s brain health website for some great tips on reducing your risk for dementia.

When presented with the choice of improving our brain health through fun activities like socializing with friends, gardening, or learning a new language, compared to doing so through a series of monotonous computer games, to me the choice seems obvious. If you want your brain to be healthier, why not make the process enjoyable too?


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