A treatment for Alzheimer’s Disease?

Alzheimer’s Disease (AD) is characterized by the accumulation of amyloid beta (Aβ) plaques within the brain (though this is generally only confirmed at autopsy). Although we don’t yet understand why these plaques form, we do know that the process isn't inevitable. Thanks to the work of Ana Griciuc of Massachusetts General Hospital and Harvard Medical School and her colleagues, we may be closer to a method of clearing Aβ from the brain before it can form plaques.

The researchers investigated the CD33 gene, which encodes a protein (CD33) that’s involved in various types of cell-cell interactions.  Although CD33 has several functions, it wasn’t previously known to do anything within the brain. Griciuc and her colleagues have now found that not only is CD33 expressed in microglial cells (the brain’s resident immune system cells) but that the amount of CD33 in the brain correlates with the number of Aβ plaques. AD patients have nearly 50% more CD33-producing microglial cells than healthy people and each of their microglial cells makes more CD33.

So AD patients have more CD33 protein and more Aβ plaques. What’s going on? To find out, the scientists looked at some mutant versions of the CD33 gene. 

Like most genes, CD33 comes in different flavors, or alleles. One in particular encodes a defective form of the CD33 protein. The researchers were able to breed mice that had only this mutant version of the CD33 gene. When Aβ was added to microglial cells from the brains of the mutant mice it was absorbed by those mutant microglia. In contrast, normal microglial cells did not absorb Aβ. 

What seems to be going on is that the microglial cells within the brain are churning out CD33. If the cells make normal functioning CD33, then those microglial cells can’t remove Aβ from the brain. If, on the other hand, the cells make defective CD33, then Aβ can be vacuumed out by the microglia. The production of CD33 somehow inhibits the uptake of Aβ by the microglial cells.

If you’re thinking that targeting CD33 might be a promising tactic for an AD cure, you’re not alone. The authors suggest sending in anti-CD33 antibodies to clear out the CD33. Alternatively, since CD33 is known to bind to sialic acid, it might be possible to throw in some extra sialic acid to keep down the levels of free CD33. Even though we’re clearly a long way away from even starting clinical trials, I find these possibilities heartening.

Griciuc, A., Serrano-Pozo, A., Parrado, A., Lesinski, A., Asselin, C., Mullin, K., Hooli, B., Choi, S., Hyman, B., & Tanzi, R. (2013). Alzheimer’s Disease Risk Gene CD33 Inhibits Microglial Uptake of Amyloid Beta Neuron DOI: 10.1016/j.neuron.2013.04.014.

Just for fun: The PhD Comics

The brilliant folks over at PhD Comics started a contest called 'Explain your Ph.D thesis in two minutes'. Having attempted this very feat not long ago, I fully appreciate anyone who can do this well. PhD Comics is in the process animating the top eleven vote getters.

This one was my favorite: Mystery Tubes in Stick Bug's Guts.



Though I do take exception to the idea that walking sticks aren't showy.

Here's an example of one of their original comics:



There's tons more stuff by the Ph.D. Comics, both videos and comics to pore over, so take your time and enjoy!

Breast cancer treatments and cognitive declines

As if women undergoing treatment for breast cancer don’t have enough problems, many of them claim to suffer from cognitive declines as a result of that treatment. But are these difficulties with memory and concentration directly caused by the treatment? A study by Patricia Ganz and her colleagues from the University of California, Los Angeles sets out to answer that question. According to this study, the good news is that chemotherapy does not appear to cause cognitive disfunction. The bad news is that radiation therapy does. Maybe.

The researchers recruited 189 women diagnosed with stage 0 through IIIA breast cancer. The patients were self-assessed for levels of depression as well as for cognitive function in four areas: memory, higher order thinking, language skills and motor-sensory perception. These evaluations occurred three times, at recruitment (and after chemotherapy and/or radiation but before the patients began any hormone therapy), six months later and six months after that. The patients were matched with data from 63 healthy controls.

Overall, about one fifth of the breast cancer patients complained of specific cognitive declines. Women were most likely to complain about memory problems if they had received radiation therapy, either with or without chemotherapy. Surprisingly, despite the expression 'chemo brain', women who only had chemotherapy did not seem to have these issues. 

I should point out that other studies have shown small cognitive deficits following chemotherapy. One group even observed changes in brain function that were visible on PET/CT scans, though that data has yet to be published. 

Personally, I don't find any of these studies to be particularly compelling, as I'll explain.

For one thing, study patients only underwent cognitive tests after chemotherapy and/or radiation. This means that we can’t compare the same women before and after they received treatment. Without that data point, it’s hard to be sure that the complaints represent true declines. Second, women with more cognitive complaints also suffered from more depression. This opens the possibility that any intellectual problems were symptoms of depression, rather than being caused by specific treatments. Finally, it’s difficult to argue that memory problems aren’t subjective when the assessments were all self-reported. These issues apply to most of the 'chemo brain' studies I looked at, not just this particular one.

So what’s the bottom line? Clearly, a large proportion of women are noticing problems with their memory and thinking abilities after receiving cancer treatment. At the very least, doctors should be prepared to discuss these symptoms with their patients. However, more experiments must be done before we know exactly what’s causing these problems.

Ganz, P., Kwan, L., Castellon, S., Oppenheim, A., Bower, J., Silverman, D., Cole, S., Irwin, M., Ancoli-Israel, S., & Belin, T. (2013). Cognitive Complaints After Breast Cancer Treatments: Examining the Relationship With Neuropsychological Test Performance JNCI Journal of the National Cancer Institute DOI: 10.1093/jnci/djt073.

You are what you breathe

What does your breath say about you? For one thing, it may one day be used to identify you. Or, more likely, it could be used as a way to assess your health. In a recent PLOS One paper, researchers from the University of Zurich and ETH Zurich show that eleven different test subjects each had unique breath signatures.

The subjects were asked to provide four breath samples per day for nine days. The participants went about their normal mouth-using activities except for thirty minutes prior to each sampling, during which they refrained from eating, drinking or brushing their teeth. None of the subjects were smokers.

At testing times, the participants breathed into a mass spectrometer that analyzed the volatile components in their breath. Take a look at the figure below. The larger image is a 3D plot of the various compounds that were detected in people’s breath. Each color and shape displays all the samples taken from that particular person.

PLoS ONE, 8 (4) DOI: 10.1371/journal.pone.0059909.

You can see two interesting things here. One, each person’s breath is distinct (though the breath of some of the subjects had fairly similar properties). Two, and perhaps even more intriguingly, nobody’s breath changed all that much over the course of the nine-day study. Unless people were eating and drinking the same things day after day, this means that what we ingest has a lot less to do with our breath than I would have thought.

The inset shows the predictive power of the spectrophotometric analysis, that is, whether the researchers could identify the subjects from their breath patterns. For example, in the top row you can see how often test subject one was matched to breath from any of the eleven participants. In that case, the correct match occurred about 80% of the time, which was more or less the average.

Of course, we’re a long way from using ‘breathprint’ analysis for either security or health screenings. Eleven people are hardly enough to confirm the idea that we all have identifiable breath signatures. As far as health goes, we don’t even know what all the compounds in breath are, let alone which ones to watch out for. Still, it’s certainly interesting to know that we may each have a stable mix of breath volatiles regardless of what we eat. That may be better news for some than for others.



Martinez-Lozano Sinues, P., Kohler, M., & Zenobi, R. (2013). Human Breath Analysis May Support the Existence of Individual Metabolic Phenotypes PLoS ONE, 8 (4) DOI: 10.1371/journal.pone.0059909.

Snowflakes like you've never seen them before

If you live in much of the world, chances are you've seen a snowflake or two. Well, you haven't seen snowflakes like this. Researchers from the University of Utah and from the Alta Center for Snow Science have developed a brand new camera system that not only photographs snowflakes at high speed, but from three different angles. They used their Multi-Angle Snowflake Camera (MASC) to capture snowflakes, (or hydrometeors, as they say in the biz) in free fall. 

Each set of three images is a single snowflake viewed from three angles by the Multi-Angle Snowflake Camera developed at the University of Utah and spinoff company Fallgatter Technologies. 

Credit: Tim Garrett, University of Utah.

The system consists of three high speed cameras, separated by 36◦ but all aimed at the same spot. If a snowflake falls through the sweet spot at the focal point, the cameras are triggered by near-infrared motion sensors. Those same detectors measure the falling speed of the snowflake as it passes by. It took two months of continuous operation and a shutter speed of 1/25,000_th of a second to obtain images like the one above.

Besides providing fascinating images, the MASC gives new insight into storm formation and duration, which depend in large part on the types of hydrometeors they contain. Snowflakes can also scatter electromagnetic waves to a greater or lesser extent depending on their shape, making this sort of data important for a variety of commercial uses.

By the way, you can buy your own MASC, if you're so inclined, from Fallgatter Technologies.

Garrett, T., Fallgatter, C., Shkurko, K., & Howlett, D. (2012). Fall speed measurement and high-resolution multi-angle photography of hydrometeors in free fall Atmospheric Measurement Techniques, 5 (11), 2625-2633 DOI: 10.5194/amt-5-2625-2012.

We need new messaging on carbon emissions

How can we get people to embrace the idea of reducing carbon emissions? By not mentioning carbon emissions, for one thing. University of Pennsylvania researchers Dena Gromet, Howard Kunreuther and Richard Larrick have found that politically conservative people are less likely to favor products that are explicitly labeled as ‘environmentally friendly’.

The researchers asked 657 people how much they supported investing in energy-efficient technologies as well as how much value they placed on three specific consequences of these technologies: reducing carbon emissions, reducing dependence on foreign oil, and lowering the price of energy. The more conservative people were, the less they liked the idea of investing in energy-efficient products. They particularly had little interest in lowering carbon emissions. They did however, like the idea of energy independence.

In the next set of experiments, 210 volunteers were given the chance to put their money where their mouths were. Each person was given $2 with which to buy a light bulb. They were given a choice between an incandescent light bulb and a compact fluorescent light (CFL) bulb. In some cases, the two bulbs were the same price ($0.50), and in others the CFL was $1.50 and the incandescent bulb was still only $0.50 (reflecting real world price differences). In either case, participants were allowed to keep the change.

The subjects were all provided with information about how much more energy-efficient the CFL bulbs were (lasting 9,000 hours longer, reducing energy costs by 75%) than the incandescent bulbs. The CFL bulbs came with either a ‘Protect the Environment’ sticker or a blank sticker. Other than this sticker, the bulbs did not explicitly mention environmental benefits.

When the two types of bulbs were the same price, all but one person chose to buy a CFL bulb regardless of sticker. Conservatives and liberals were equally likely to buy CFL bulbs costing three times as much as incandescent bulbs when those CFL bulbs came with a blank sticker. Apparently, under neutral conditions, anyone can see the value in a product that lasts ten times as long for only three times as much money. However, unlike liberals, conservatives were less likely to choose the more expensive CFL bulbs if those bulbs were accompanied by an environmental label. This suggests that idealogically conservative people would rather pay more than be associated with protecting the environment. 

Although I could take this as rather depressing news, I think it’s important to be aware of these attitudes. If people don’t care about protecting the environment or reducing carbon emissions but do care about energy independence and cost efficiency, then by all means, let’s focus on those attributes. After all, energy-efficient technologies will provide all those benefits.

Gromet, D., Kunreuther, H., & Larrick, R. (2013). Political ideology affects energy-efficiency attitudes and choices Proceedings of the National Academy of Sciences DOI: 10.1073/pnas.1218453110.

Just for fun: Model birds

You may think you've seen model birds before, but you haven't seen them like Johan Scherft makes them. Just look at this goldfinch:



Would you guess it's made of paper? 

If you want to see how he does it, check out this tutorial:



Easy peasy, right?