Artificial turf and soccer

Before I start writing out whether or not playing soccer on artificial turf (AT) leads to injury, I have to admit that this was a real learning experience for me. For years, I've been convinced that playing on turf leads to higher chances for injury. So much so, that I repeated that on at least three radio shows last summer, during the women's World Cup.

But, that's why I love science. It proves me wrong all the time, and reminds me about how little I really know. It's humbling, wondrous and informative.

Just like my recent blog post on heading and youth soccer, I will be linking to the abstract of various articles. If you would like access to a particular paper in it's entirety, tweet me at @AlzBlog101 and I would be happy to send it to you.

1. What is Artificial Turf (AT)?

It's a playing surface used for sports such as field hockey, soccer, american football, etc. AT is made of synthetic fibers that look like grass. However, for countries where maintenance of natural grass is problematic due to non-ideal temperatures, AT has proven to be an alternative.

2. How did the idea that AT leads to increase in soccer injuries start?

While there were probably anecdotal reports, the first study that examined this issue was Arnason et al. (1996) . They found that the propensity for injury increased on AT vs natural grass.

3. Were the Arnason results replicated by other studies?

No. There have been many studies that suggest that there is no difference between injury risk of AT vs natural grass. These can be found here --- Ekstrand et al. (2006), Steffen et al. (2007), Fuller et al. (2007), Aoki et al. (2010), Bjorneboe et al. (2010), Kristenson et al. (2013) .

In essence, almost all studies suggest that the risk for injury does not increase for athletes playing on artificial turf. It's important to note that the studies cited above cover the gamut from NCAA soccer players to professional footballers - both male and female. So, there isn't a bias in terms of the level that the game is being played.

Here's something even more surprising. There have been studies that suggest that playing on artificial grass may be linked to LOWER injury rates than natural grass. Those can be found here --- Ekstrand et al. (2006), Soligard et al. (2012), Williams et al. (2013), Almutawa et al. (2014), Meyers (2013).

4. Okay, so playing soccer on AT is better than on natural grass?

Not so fast. You see, the articles cited above look at injuries as a whole. It's still possible that there are differences in particular injuries. A good analogy is that the articles above are looking at the injury issue at a whole-forest level. Whereas, in order to understand the risk for specific injuries, we have to go down to the tree-level.

5. Have there been studies that look at specific injuries in terms of artificial turf?

Yes.

6. What did they find?

The big one is that AT seems to be bad news bears for your ankle! Ekstrand et al. (2006), Steffen et al. (2007), Ekstrand et al. (2011) all found that playing on AT leads to an increase in ankle injuries in soccer players. For the sake of completion, it is important to note that Soligard et al. (2012) found the opposite - a reduction in ankle injury in soccer players playing on AT.

Hagglund et al. (2011) found that there was no difference between AT and natural grass surface for risk of patellar tendinitis (that's a fancy way of saying pain caused by inflammation in the knee).

Ekstrand et al. (2011) found that male soccer players were less likely to have a quad injury when playing on AT vs natural grass.

7. Woah! Getting too much. Summarize this for me.

Essentially, there is no increase in overall risk for injuries when playing on artificial turf vs natural grass; in fact, some studies suggest that it may be better overall than grass. However, there's general consensus that playing on AT may be a risk factor for ankle injuries, in particular. So, watch those ankles, friends!

8. So why does this myth about AT persist?

There are some general reasons - such as the naturalistic fallacy - where people believe that just because something is natural, it is automatically better than something synthetic or artificially manufactured.

Another reason is that we tend to extrapolate results from other sports into soccer. A perfect example of this is comparing football injuries to soccer. Both can be played on AT and therefore, when we see a study that suggests that injury X is increased in football, we assume incidence of injury X is also increased in soccer.

However, the sports are drastically difference and this assumption isn't necessarily true. For example, Balazs (2015) performed an examination of the literature, and found that playing on AT results in an increased risk for anterior-cruciate ligament (ACL) injuries in american football, but not soccer players. Therefore we should be careful to not over-interpret data seen in other sports played on AT.



So, lesson learned from my perspective - always fact-check everything. Especially things that I "know" are true.

Heading in youth soccer: what the science says

Recently, the United States Soccer Federation (USSF) released a report advising the elimination of heading in soccer for kids under the age of 10. And recommends that full-contact heading not be allowed till athletes get to 16 years of age.

Now, while everyone is on board with the idea that player safety is very important, particularly that of children and young adults, there has been much debate over whether the guidelines would benefit athletes and soccer in the long-term.

Let me start by saying that I believe that concussions in soccer are a serious, serious, serious, serious, serious, serious, serious concern. Is that serious enough? I believe that concussions are currently being managed incorrectly by the Football Associations and FIFA. And that things need to change rapidly so that our soccer players can live a healthy life after they retire. However, today, we will be focusing on the topic of concussions in youth soccer players.

While one can have a myriad of personal opinions on this topic, and certainly, I do, too (I'll discuss those later), the majority of this post will look at what the scientific literature says re: Heading in youth soccer. I understand that many do not have access to the articles I'm citing here, so I will link to the abstract (which is available to all), and if you are interested in a particular article, tweet at me, and I'll send it to you.

1. Can heading the ball lead to concussions in high school players?

Yes. It isn't the most common form of concussive injury in youth soccer players, but, it is certainly possible (Cornstock et al, 2015 ). However, what this study does not look at  is HOW those ball-to-head related concussions were procured. That is a key caveat to this study.

There is another study that suggests that zero concussions were produced by heading the ball correctly, and all were a result of the ball striking an unprepared player at close distance (Boden, 1998) .

2. Can heading the ball lead to concussions in youth soccer players?

Doesn't seem like it. Here's a key excerpt from a book chapter  ---

"Dr. Kirkendall . . . calculated the impact of a soccer ball on the head of youths of various sizes, based on the likely speed of the ball, and concluded that the force of impact is well below the force that is thought to be necessary to cause a concussion in heading a soccer ball." --- Dr. Donald Kirkendall, Causes of head injuries in soccer .

Even in U14's soccer, there is likely not enough ball velocity to cause concussion (Hanlon and Bir, 2012) .

A meta-analysis (looking at various studies between athletes 10-24) suggested heading the ball was unlikely to cause injuries (Pickett et al., 2005).

Essentially, those kids do not kick the ball hard enough to cause the G-forces (acceleration forces) to result in concussive injuries.

3. What about subconcussive injuries from heading?

In order to answer this, a quick primer on subconcussive injuries: It is an emerging area of research that suggests that repeated impact to the brain can result in brain damage, even though concussion hasn't occurred. The problem with studying subconcussive injuries is - how do you tell if someone has one? Neuroscience tackles this in a couple of ways. Firstly, we have identified certain biomarkers (biological red flags) to suggest if someone is exhibiting hallmarks of disease. The second technique is to look at behavioral tests that suggest whether someone is cognitively impaired. The assumption being, in both cases, if subconcussive injuries have occurred, there will be a biological (biomarker) and/or behavioral (neurocognitive) change.

Coming back to the original question. Most literature suggests that heading the ball does NOT lead to changes in biomarkers/neurocognition. These can be found here --- Kontos et al. (2011), Stephens et al. (2005), Kaminski et al. (2007), Broglio et al. (2004), Guskiewicz et al. (2002) and others.

But, this study, does suggest that a cognitive change may occur - Zhang et al. (2013) . I have to state a caveat - this Zhang study is poor. The effect size (how different the soccer-playing and non-soccer-playing groups were from each other) is very small. For my science friends - they set a non-one sided gaussian t-test alpha of 0.1, which is an immediate red flag. For my non-science friends - I think the effect they observe is not worth believing.

4. Okay, that's a lot of words. What's the gist?

Currently, a preponderance of the literature does not support the idea that heading the ball leads to subconcussive injuries in youth (kids - high school) soccer players.

5. Is that a definitive no then?

Not quite. You see, the work surround subconcussive injuries is nascent. And, as such, has caveats. For example, some of the behavioral tests and biomarker tests need further validation. Therefore, it is theoretically possible that subconcussive injuries ARE occurring, but our tests aren't well enough designed to detect them... just yet.

6. What about the report of the kid who almost died after heading the ball?

That's a real report. That happened a few years ago, and no one has contradicted the young man's claim that his subdural hematoma (potentially fatal bleed in the brain) was the result of a single header (Lutfi et al., 2009). My concern is that the report says he headed the goalkick with the "front" of his head. I am not sure if this means with his forehead (which would be the correct way to head the ball), or with the top of the head (incorrect, and unfortunately seen in young soccer players who haven't practiced heading).

7. What about player to player contact?

Yes, this often is the culprit for concussions. Most of the articles I've linked to above suggests the same. These injuries can be a result of two players going for a header, or accidental contact with one player's knee, while the other is on the ground, etc. There are a myriad of ways that player to player contact can result in head injury and concussion.

Head to head injury is a serious concern

Okay, now we are going away from the realm of scientific literature into my own opinion (using the literature I've read as a basis, of course)

8. So, what's the solution?

In my opinion, there should be a serious punishment for serious player to player contact. In the last 3-4 years, the concept of "out of control" tackling has come into play.

You see, while I was growing up, the definition of a good tackle was "getting the ball". If a player got the ball before he made contact with the player, it was deemed a good tackle - regardless of whether this involved excessive force or injury to the opposing player. However, now, even if a player wins the ball, if he comes in with excessive force, tackles from behind or uses two-feet, the referee usually punishes the tackler with a red card (FIFA, law 12) . Why? Because all of those conditions are optimal for causing injury.

Similarly, excessive force, using elbows, out of control contact with an opposing player's head (knee-head, for example) should be deemed dangerous play, and therefore a red card. This would result in players being careful of so-called 50-50 balls, and wary of using their elbows as leverage.

9. But, what about heading itself?

I respect people's opinion who think "well, removing heading in youth players won't hurt". But, in my opinion, having young kids learn how to head the ball early would lead to developing the appropriate neck muscles needed (Gutierrez et al., 2014) to prevent head injury in the future. If heading the ball isn't being introduced to them until they are 14, this may lead to an INCREASE in the number of concussions. Because, by the time they're 14, they are kicking the ball much harder, and have yet to learn the basics of heading.

Incorrect way to head the ball. (Image via http://hubpages.com/sports/Soccer-Head-Injuries-in-Children-Brain-Damage-from-Heading)

10. To summarize:

1. Preponderance of scientific literature does not support the idea that heading can lead to concussions or subconcussive injuries in soccer players.
2. More work needs to be done.
3. In order to minimize concussion, new rules regarding player contact need to be made.

Day 3 - MicroRNA Monday

Usually Mondays are the worst. But, not today!! It's SFN!!!

There were quite a few microRNA posters I attended today. In case you might not know what they are, here's a quick synopsis of what microRNA are --

microRNA (miRNA) are short strands of RNA that modulate protein expression. To give you an analogy if proteins are lights in a room, miRNA are the dimmer switch. They don't turn the light on or off, but they help ensure that the light isn't too bright, or too dim. 

Here were the highlights of today's events ---

Morning session

1. Minano-Molina (C45) - Found that miR-92-3p, miR-181c-5p, miR-210-3p modulation in Alzheimer's transgenic mice.

2. Edler (C20) - Abeta and tau pathology increases with age in chimpanzees. Studies in primates are becoming rare - for ethical reasons. This study was done with primate brains donated by zoos and research institutions.

3. Bicca (C20) - TRPA1 levels in AD mice are changed - possibly via a response to oxidative stress.

4. DeVito (Z26) - This was my favorite poster of the day. 142-3p involvement in a mouse model of Multiple Sclerosis. They found that 142-3p knockout mice show reduced symptoms associated with the mouse model of MS. The target for this miRNA was the mRNA coding for GLAST (glutamate aspartate transporter). They also found that anti-miR-132 - administered via an osmotic mini pump) help reduce symptoms in the MS mouse. I enjoyed that their group covered the miRNA work from basic, in vitro predictions, all the way to in vivo administration of the miRNA. 

Lunch -

None. Not happy about it. Still.

Afternoon session

I presented my poster all afternoon. It was D25 - microRNA298 -  a dual regulator of proteins involved in Alzheimer's Disease.

SFN Banter

Met some people I have been interacting with on twitter. Remembered that I am incredibly socially awkward in large groups. Also, very jealous of those people who are able to walk up to strangers and engage them in conversation. You know - extroverts.

What did you enjoy about your Monday at SFN?

Day 2 of SFN - Crashing helmets on Stampede Sunday

Stampede Sunday, as I like to call it, was as packed as it is each year. 

There was lots of cool science to talk about and cool scientists to talk about it with. Here with the highlights ---

1. Hendrix (DD56) – Her aim was to raise awareness for her local “brain awareness day”. She was able to do by promoting via social media and designing flyers. She also talked about having visited Capitol Hill and talking to policy-makers about the changing funding climate. Basically, Ms. Hendrix is an advocate for both neuroscience and neuroscientists. We need more people like her. Follow her @RDHendrix.

2. Brager (DD38) – a fellow blogger, her poster showed that cryotherapy increases both the amount as well as the quality of sleep in athletes. Sleep remains an underappreciated area of neuroscience and I saw some other cool work looking at sleep disruption in rodent models. Brager’s work was particularly fascinating because it was in athletes; something many of us ex-athletes can appreciate. Basically - those ice baths are really, really important for recovery. And, if possible, a cryo chambers is even better. 

3. Whitesall (D31) – Working at the Allen Institute, Ms. Whitesall’s work looked at Default Mode Network (DMN) in the mouse brain. In recent years, the idea of the Default Mode – essentially, the baseline of your brain activity – has become apparent. It makes for both interesting science, as well as interesting science fiction. Whitesall’s work hypothesizes that the brain regions comprising the DMN may be one of the first to perturbed in Alzhiemer’s Disease. She will test whether this is true in an AD transgenic mouse line.

4. Kawarabayashi – Looking at tg mice models, they found that PrPc, Abeta mono and dimers, Fyn, NMDA, GSK3beta and pTau all localized in lipid rafts! This ties in both the possible involvement of lipid rafts in AD, as well as seemed to support the amyloid hypothesis.

5. Graham (C87) – Western diet in APP/PS1 mice increases A-beta load and TREM2 activation. TREM2 is the new baby in the AD field, and there will be a lot of work on it. And, as for western diet, STOP BEING SUCH FATTIES, YOU GUYS. And, by you, i mean, me.

6. Brkic (C86) – Omega-3-Fatty Acids have beneficial effects on brain of AD mice – by reducing amyloid plaque burden. There was recently a longitudinal study that determined that fish oil showed no benefit for cognition in AD patients. Brkic informed me that she thought that study was done with patients who has advanced AD, and therefore, an amelioration of symptoms would have been lost in the noise of progressed neurodegeneration. I agree with her. Most AD therapies should be looking at helping decelerate the pathology in mild cognitive impairment patients, in my opinion.

7. Colello (C91) – This was my favorite poster of the day. Their group decided to address the issue of the g-forces experienced by helmet to helmet collisions in football players. They posit doing so by placing repulsive magnets in the helmet of players. This would lead to the generation of a repulsive force that would reduce the g-forces. Their proof of concept suggests that they are able to reduce g-forces (measured by accelerometers) in a rig where they are essentially crashing two helmets together. This is fascinating work! And, a perfect example of how invention often come from people who cross disciplines.

Lunch

All the places close by were closed! Stampede Sunday is the worst. I ate a sandwich from a grocery store. It was awful.

Afternoon sesh

I spent the entire time presenting the boss-man's poster.

What were your highlights from today? My poster is tomorrow (Afternoon session, D25). Stop by and say hi!

Day 1 - Soccer in the morning, Neuroscience all afternoon

I started the day early, in order to attend a couple of networking sessions and to watch soccer, in peace, on my laptop. Luckily, the team I support - Manchester United - won comfortably, which ensured that I was in an amicable mood all day.

While watching United play, I met Dr. Ferchmin, who informed me that he has been attending SFN conferences since the mid-70s. And, that's pretty neat. He must have watched, first-hand, some of the breakthrough work, particularly in the mid-90s - when neuroscience hit it's first boom.


Morning session
The official "kickoff" ceremony for SFN this year was a lecture by Judge Jed (his name is suspiciously similar to Judge Dredd)

Judge Jed? Dredd? Jredd?

Judge Jed Rakoff discussed the relevance and somewhat uncomfortable relationship between neuroscience and the judiciary. He cited the history of eugenics, Freudian idealogies, lobotomies, etc. to underline the necessity for a skeptical look at what neuroscience tells us.

Personally, I believe that Judge Rakoff may have conflated some history that is more relevant to psychology than it is to neuroscience, but his overall point is still valid. Science is not a perfect machine. Things that we consider to be true today, may be experimentally precluded in 5 years. However, the necessity to commit to neuroscience - as a self-correcting discipline - is essential. And, I think Judge Rakoff did a commendable job of reiterating that fact. Especially, since he was sitting in a room of neuroscientists - who would not have been pleased to hear him tear down their life's work!

Lunch

Overpriced, overrated.

Afternoon session
I was excited to run in to my friends from the On Your Mind podcast on the way to the poster session. Kathryn and Liam are two Canadian neuroscientists who started this podcast about 2 years ago. The podcast starts with a discussion about current topics in neuroscience, and ends with a discussion of an interesting neuroscience paper. They often have great guests who bring their own interests to the table, thereby increasing the list of topics covered. I highly recommend you check them out.

In between limping through poster sessions, I found the following posters worth highlighting (I apologize if I misspelled any of your names; my handwriting is horrible) ---

1. Teneka Jean-Louis (#B90) - Prostaglandins impair APP glycosylation. The Post-translational modification of APP, in my opinion, is an area of research that requires much more understanding. As, many of you are aware, APP is the protein from which A-beta is excised.

2. Caverly (#B93?) - While they did not manage to address their primary hypothesis, they found that buffering A-beta does improve memory in Alzheimer's transgenic mice. ONE FOR THE AMYLOID HYPOTHESIS!

3. Bachsetter (#B109) - Microglia in human AD brain are very different - in terms of morphology and biomarkers. This is important because we often tend to treat microglia as one homogeneous population. And, their group shows that they are not.

4. Harach (#C27) - This was my favorite poster of the day! They suggest that our gut microbiota may play a role in generating AD pathology. They are not sure of the mechanism, but, they believe that it is related to inflammation.

5. Moore (#D12) - They found that athletes with a history of concussion exhibited alterations in EEG signature. While this is not surprising, they found that these abnormalities extended longer than the recommended "Grace period" for athletes. Therefore, it's possible that when we tell athletes that they need to take 2 weeks off after a concussion, that may NOT be long enough.

6. Kitko (DP02) - Using quantum dots as a way to improve in vivo visualization. I'll admit, I didn't quite understand the details of this, but it definitely looked cool! One for the biophysicists.

7. Moses (G27) - Addicts who performed well on a memory task, seemed to have a better ability to abstain from drug relapse. A bit paradoxical to me - I always assumed that memory triggers would be a key reason behind drug relapse, and therefore, a reduction in memory recall would be beneficial to treating addiction. Goes to show - our intuition isn't always correct, and mine wasn't in this case.



What did YOU enjoy today? Let me know if you'd like for me to stop by your poster/symposia tomorrow. Enjoy your Saturday in Chicago!

Day 0 - Arriving in Chicago

My lab-mate, Baindu and I left Indianapolis about 4PM and, on our way, Baindu introduced me to some new Justin Beiber music. Yes, I listened to Justin Beiber. Does that make me a Belieber? Speaking of music, Beach House's new album just dropped today. If you haven't listened to Beach House before, do yourself a favor and check them out. Start with the album "Bloom".

We got to Chicago just in time for stand still traffic. We drove past McCormick Place on our way to our hotel, and we marveled at the size of it. After navigating the insane traffic, we checked into our hotel, only to find out that wi-fi isn't free.

In 2015.

It's 2015.

Wi-fi should be free.

In 2015.

So, here I am, in the lobby of our hotel, where fellow neuroscientists sit around me - complaining about the lack of Wi-Fi. Also, it's 2015.

I'm really looking forward to tomorrow. The day will start early , and I'll plan on getting to the conference about 8AM. No, I'm not an over-achiever; I just want to squeeze in a professional session before I watch soccer on my computer from 9AM-11AM.

You know, using the free wi-fi that McCormick Place provides.

After that, I'm going to shuffle between a few Nanosymposia on Alzheimer's Disease: Experimental therapies, and a few interesting posters on TBI and AD.

What are you guys going to visit tomorrow?

Welcome, fellow neuroscientists!

It is my privilege to welcome you to my blog. I am looking forward to experiencing the SFN meeting with all of you. I would love to talk to you about your research at the meeting. Please let me know the date and time of your poster, and I'll stop by and blog about it!

About my blog: My aim is to explain the basic tenets of Alzheimer's to a non-scientific audience. I feel as though I'm learning as I go along. Your feedback would be appreciated, of course. You can follow the blog updates at @AlzBlog101 

About me: I am a 6th year graduate student in the laboratory of Dr. Debomoy Lahiri at IU School of Medicine. My research looks at the microRNA regulation of proteins implicated in the pathology of Alzheimer's Disease.  You can find me on twitter at @NipunChopra7

During the meeting: I aim to have daily summaries of exciting posters/symposia. I will tend to focus on Alzheimer's and Chronic traumatic encephalopathy/Traumatic Brain Injury - as those are my areas of interest. But, I am genuinely fascinated by all things neuroscience. So, please let me know if you'd like for me to stop by and chat with you.


Posts so far have been ---

1. Introduction
2. Key terms in AD
3. The insidious beta-amyloid
4. The tangles of tau
5. Taking pictures of your brain - guest post from Joey Contreras

Thanks for stopping by! And, I hope you bookmark this page. Thank you to the SFN committee for selecting my blog as one of the featured blogs at the meeting.

Taking pictures of your brain - MRIs and Alzheimer's Disease

Currently, the only confirmation of Alzheimer's Disease is made post-mortem; by looking at the brain after death. Additionally, current therapies seem to work best when Alzheimer's is not in an advanced stage. Therefore, early, accurate diagnoses of Alzheimer's is crucial to the welfare and caregiving of patients.

Although there are other possibilities, neuroimaging is arguably the best candidate for early detection of Alzheimer's. 'Imaging' is just a fancy way of saying 'let me take a picture'. Neuroimaging, therefore, is the ability to take a picture of your nervous system. In this case, we're talking about the brain.

Since this isn't my area of expertise, I was thrilled that my friend and fellow graduate student, Ms. Joey Contreras (@JoeyAnnette) agreed to answer some basic questions about neuroimaging in Alzheimer's Disease. Joey is doing her grad work in a lab that is well-renowned for terrific work in neuroimaging in Alzheimer's and other disorders. 

1.    What is an MRI?

MRI stands for Magnetic Resonance Imaging. An MRI scanner uses magnetic fields and radio waves to be able to form images of structures within the body, like the brain. This technique is really helpful in medical imaging research because it’s a non-invasive, safe procedure that does not require exposure to any radiation (like positron emission tomography, PET). 

When MRI is applied to the investigation of brain disorders we call this “neuroimaging” and it’s often the tool of choice because you can visualize and differentiate between different types of brain tissue. The two major types of brain tissue are called grey matter and white matter. 

Grey matter (GM), which is normally a pinkish grey color in a living brain, is the part that contains all the cell bodies, dendrites, and axon terminals of neurons (highlighted with red arrow). The other major tissue in the brain is referred to as white matter (WM). White matter is named because of its whitish color, which is made up of axons connecting different parts of grey matter to each other (shown by the blue arrow). Basically, these axons are like the major highways for information to travel in the brain. The green arrow denotes cerebral spinal fluid (CSF), which acts as a cushion, protecting the brain and spine from injury.

            During Alzheimer’s disease (AD) the brain experiences major damage in the form of overall loss of grey matter as well as loss of or abnormal WM. Additionally, abnormalities in GM and WM have been found to be correlated with cognitive decline (a major indicator of disease progression with Alzheimer’s disease). In this regard, its important to get a comprehensive picture of exactly what changes are occurring as the disease progresses and even before diagnosis occurs, this is where getting a good picture of brain can help.  

To speak on this a little more, the problem with Alzheimer’s disease is that by the time you start to notice cognitive decline (noticeable memory loss) years of underlying abnormal neuropathology may already have occurred.  Using neuroimaging techniques, we may be able to detect a problem even before the patient does if they come in early enough.

2. What is an fMRI

Similar to MRI, fMRI stands for functional magnetic resonance imaging. This type of imaging is unique in that it measures brain activity by detecting changes in blood flow in different areas of the brain. This technique takes advantage of the fact that when an area of the brain is in use, blood flow to that region will be greater.  This is what’s essentially called a BOLD (blood-oxygen-level dependent) signal.  

The advantage of fMRI over MRI is that fMRI can monitor brain activity and detect functional differences in brain regions when the brain in engaged in a task (ie, memory task, motor task, etc) or disengaged (at rest).  In terms of diagnosing Alzheimer’s disease, there is no single test that can be used. As a result, a medical evaluation which includes past and current medical standing, mental status, physical and neurological exams, blood tests, and of course brain imaging data (fMRI, MRI etc) go into establishing a diagnosis.

            Often times when MRI is used to aid in diagnosing AD.  It does so by looking for similar patterns such as a reduction in grey matter (indicated by red circle in top image, and arrows in bottom image ), resulting in enlarged ventricles (indicated by red arrows in top image) and overall dramatic volumetric loss in medial temporal lobes.

In terms of helping diagnosis AD, fMRI is a bit less straightforward. However, there is a lot of evidence to suggest the carriers of the e4 allele of the apolipoprotien E (APOE) gene (associated with increased risk for late-onset AD) correlate strongly with functional brain activation patterns in older adults despite normal cognitive abilities (Bookheimer et al, 2000),. This would suggest that fMRI can help elucidate changes in the brain that would otherwise be undetectable in a high-risk population for AD (for more in depth review on this look for Rishacher et al, 2013)

3. What are the problems with the field that have hampered progress in diagnosing AD?

            Imaging studies involving neurodegenerative diseases and dementias such as AD are very informative regarding structural and functional changes in  the brain which are underlie the observed clinical symptoms such as cognitive decline. They play an important role in aiding and supplementing additional data for making an accurate diagnosis as well as ruling out other diagnoses. Further studies with advanced MRI and fMRI techniques will likely provide even more information about pathology associated with AD. 

However the problem now is that these techniques are still relatively new in a young field (neuroscience). As a result there is a lot more room for improvement and accuracy. For instance, resolution is something that the field of neuroimaging still struggles with immensely. Think of it in terms of TV screens. When the TV first came the image was pixelated and fuzzy. This is very true for MRI and fMRI but instead of pixels we have something called voxels. 

Voxels are essentially a 3D pixel and the smaller the voxel the more accurate the picture. As time progresses we, as a field, are getting better at this going from a 5 mm³ voxel to current 1 mm³ voxels or smaller. Better resolution means more accurate representation of brain tissue in both time and space, which is incredibly important if we want to make accurate diagnostic boundaries.  We also need to do a better job in terms of identifying and using appropriate statistical methods that will allow us to analyze and integrate large imaging data sets and different types of imaging data.

4.    How do you see the field of neuroimaging contributing to the diagnosis/treatment of Alzheimer’s in the future

  Neuroimaging has major potential. In the last 10 years we have seen exponential growth in this area as well as the emergence of a new field called brain connectomics. Brain connectomics is the marriage of network science theory with neuroimaging.

 Basically, this field uses information from MRI, fMRI and other imaging sequences (which I can go into at another time) and analyze it in a new way, helping to predict how information flows and model anatomical and functional pathways in the brain.  

The field of neuroimaging and brain connectomics holds promise in two ways. First, it will be able to identify early pathological changes that may otherwise have been undetectable. Second, we could also use fMRI to assess the effects of various treatments (e.q. get a baseline assessment of functional brain changes and comparing that to how that same brain might change or improve with treatment). 

This would allow us to better monitor and personalize treatments for patients.  Basically this field has the potential to better predict cognitive impairment, even before the onset of clinical symptoms, creating promising biomarkers for understanding AD.

--------------------------------------------------------------------------------------------------------------------

Thanks, Joey!! 

Joey's work:

The goal of my project is to identify and characterize the subtle changes that occur in both structural and functional connectivity in the brain during the early prodromal to clinical stages of Alzheimer’s disease (AD). Recent evidence indicates that cognitive alterations as well as anatomical abnormalities in AD begin manifesting years before they can be detected by traditional methods. In order to assess the brain from a systems perspective, I have begun to use brain connectomics (a very powerful methodology that relies on network science). This allows me to assess and understand how brain networks are affected at different stages of neurodegeneration. 

The tangles of tau - breaking down highways

In a stereotypical brain from an Alzheimer's patient, there is the presence of amyloid plaque and tau tangles. We have already covered amyloid deposits in a previous post. Today, we will be discussing this tau thing. What is it? And, what the heck does it have to do with Alzheimer's Disease?

What is the link between Alzheimer's Disease and tau protein?

Post-mortem brains from Alzheimer's patients often have tau tangles (also called neurofibrillary tangles. The pictures below shows a magnified version of what these tangles look like (tau tangles are on the right, amyloid deposits on the left).

Image taken from bigthink.com

What are tau tangles aka neurofibrillary tangles?

These tangles are composed of a bunch of abnormal tau protein stuck together.

What is tau? why does it clump together during Alzheimer's Disease?

In order to answer this question, I think we should first go over what microtubules are. Microtubules allow the transport of materials across the neurons.

Here is an analogy - if your neuron is a city, then microtubules are the roads. You see, your neuron is constantly making stuff that it needs to send to different parts of the cell. One way to do that would be to simply make something and let it diffuse through the cell. But, this would not be very efficient. Therefore, the cell sets up it's own roadways in order to keep delivery organized and efficient.

Here's the really neat thing. These roadways are entirely dynamic! If the cell is done sending one protein to one part of the cell, it can send workers to that road and break down that roadway.

From Nature Reviews

And this is where tau becomes important. You see, what tau does, it helps the workers know whether or not to break a highway down. Sort of like a beacon to say - this road needs to stay!

Microtubules - the roadway of cells. (Image taken from absoluterights.com)

What happens to tau in AD?

Tau gets hyperphosphorylated in AD.

Wait, stop using big words, you showoff. What does that 'phosphorylation' mean?

Phosphorylation occurs when a phosphate group is thrown onto a protein.

Every protein in every cell of your body is under tight control. This is because, evolution has ensured that every protein can be made, destroyed or made to disappear as the cell needs it. Phosphorylation is one of these regulatory processes. By throwing a phosphate group onto a protein, you can change what that protein is doing.

Okay, what does phosphorylation do to tau?

Well, here's the weird thing about tau, it can exist in three forms---

1. Unphosphorylated - this is the form we have been talking about - when this form is present, the cell knows that that roadway needs to stay.

2. Phosphorylated - This is the green signal for the roadway to be taken apart. Let me reiterate, that this is normal. This phosphorylation-unphosphorylation allows the dynamic rearrangement of the roads in the cell.

3. Hyperphosphorylated - This is bad news bears. This is when the tau starts to misbehave and clumps together.

Okay, this is getting too sciency again. What are you even talking about?

Here's the gist so far - Tau is important to maintain normal function in the cell. During Alzheimer's this protein gets too many phosphate groups put on it. This makes the cell lose a bunch of it's roadways for no good reason.

And, what's worse is that all that hyperphosphorylated tau starts to clump together and form those aforementioned tau tangles.

What do these tau tangles do that's so bad?

Just like the amyloid plaque story, this isn't so cut and dry. Many believe that these deposits lead downstream to neuronal death. And, as we've discussed earlier, neuronal death is a key component of the cognitive issues in Alzheimer's Disease.

Is there a link between this tau stuff and the a-beta stuff?

Yes, there have been many studies that show that a-beta can actually lead to tau hyperphosphorylation (the bad version of tau). There are also a small number of studies, that are studying whether the converse is true - that tau can affect a-beta production.

Can we reduce this hyperphosphorylation?

There have been attempts to target the things that regulate the phosphorylation of tau. These have had limited to no success.

Okay, I'm bored. Summarize this.

Okay, here goes. Tau itself is not bad. The neuron needs it. But, for reasons that remain unclear, tau converts to a form (hyperphosphorylated). And this form arguably leads to cell death. And that, in turn leads to the tau tangles we observe in the brains of Alzheimer's patients.


Let me know what you guys think. Did anything still seem confusing? Please reach out to me at @AlzBlog101 or @NipunChopra7 .

The insidious beta-amyloid

First of all, thank you for all your feedback and constructive criticism. I aim to incorporate those into my writing and hopefully continue to make the writing both informative and devoid of too much neuroscience jargon.

One of the post-mortem hallmarks of Alzheimer's disease is the presence of amyloid plaques (also called senile plaques, neuritic plaques, etc.). For over 3 decades, researchers have been trying to understand what these plaques are made of, and how they contribute to the pathology of Alzheimer's Disease.

Today's blog post will explore questions about these plaques and their insidious component - beta-amyloid.

What are plaques made of?

Plaque usually means "sticky material.". Amyloid plaque is made of oligomerized beta-amyloid strands. That is just a fancy way of saying - a bunch of beta-amyloid stuck together.

What is beta-amyloid?

It's a short fragment of a larger protein, which is potentially toxic in Alzheimer's Disease.

What causes this beta-amyloid to stick together?

Bits of beta-amyloid clump together due to certain chemical properties that each strand has. An easy analogy is if you have a dog, you know that dog hair tends to clump together (and form, what my roommate calls 'bales' of hair). So, essentially, these bits of beta-amyloid clump together and form larger bits of beta-amyloid, which, in turn, form the larger plaque.

Dog hair - in case you're like my mom and hate dogs (and have therefore never seen it clump together). Love you, momsie!

What causes the singular beta-amyloid to form in the first place?

Beta-amyloid is cut out from a larger parent protein called Amyloid Precursor Protein (APP).

Why is APP being cut in the first place? Why not just get rid of it entirely?

When APP is cut in the 'right' way, fragments are made which are important to normal processes of the neuron. Therefore, getting rid of it entirely (even if we could it) would have deleterious effects on the normal function of neurons.

What cuts the amyloid-beta fragment out of APP?

There are enzymes in cells that play a variety of functions. A few enzymes are capable of cutting APP at distinct spots, releasing fragments of differing lengths. In this figure below, the blue fragment is the APP protein, and the little green fragment is the harmful beta-amyloid fragment. The scissors, represent 2 enzymes that cut it out.

Cleavage of APP by enzymes (Credit - McGill University)

An analogy might help here. If you consider APP to be a long string in length, depending on where along the string two sequential cuts are made, you would get fragments of differing lengths. The length of these fragments are crucial - because they determine whether beta-amyloid will form, or other largely non-toxic fragments are formed.

Okay, this is getting complicated, give me a summary, Nipun

Amyloid plaque is composed of beta-amyloid fragments. These fragments are cut out of a larger protein called APP by certain enzymes.

What does amyloid plaque do? 

This is where the story gets interesting (note: whenever a scientist says "interesting", he/she means - "controversial").

Let's take the traditional position first. Many believe that amyloid plaque disrupts normal cellular function and this leads to cell death. How? Well, it's possible that this plaque inserts into the cell membrane disrupting the balance of electric charge between the inside and outside of the cell.

Or, amyloid plaque may activate reactions inside the neuron that lead to it's death. Imagine the cell as your apartment, and a receptor (refer to post #1 for a better understanding of a receptor) as your doorbell. Normally, when someone rings your doorbell, you look through your peep-hole, see that it's your boyfriend/girlfriend, and all is well. In your neurons this is a normal, beneficial protein binding to the receptor and saying, "Okay this is business as usual, carry on."

But, imagine if the doorbell rang, and you realized this was at your door ---

(Insidious Donald Trump = insidious a-beta. Photo credit - greenrushinvestors.com)

That face would send anyone into a frenzy. You might even consider blowing up your own house, just so you don't have to interact with THAT HAIR. Well, that's what the cell decides to do - it sees beta-amyloid and decides to shut down shop to protect other cells nearby.

Or, it may attract the attention of your immune system which would, in turn, lead to more of the aforementioned Donald Trump effects. (If only there was an immune system that would take out the trash that is Donald Trump, amirite?)

FYI - Fellow grad students, check out Sakono and Zako (2010) for a review on A-beta formation (http://onlinelibrary.wiley.com/doi/10.1111/j.1742-4658.2010.07568.x/epdf), if you want to read more.

So, what's the controversy?

Well, you see, there are those who believe that beta-amyloid has nothing to do with causing the disease at all. They believe, that this beta-amyloid is a consequence of the disease, not a cause of it. You know - what came first, the chicken or the egg*?

The chicken or the egg* (Image credit: The Guardian)

Is there any evidence to support this? Actually, yes. You see, there are patients who have normal levels of plaques, but advanced Alzheimer's Disease. As a corollary, there are those who have amyloid plaque hallmarks in their brain (post-mortem), but never showed the cognitive decline correlated with Alzheimer's Disease.

Why do we care? Why not just try to treat it anyway?

If amyloid plaque comes after whatever is causing the disease, reducing levels of plaque would have no impact on the disease. 

Should we waste all that funding (and all those countless graduate student hours) on what is potentially a dead end?

YES! Along with the topic of tau tangles (next week's post), Amyloid plaque is our best target for the treatment of Alzheimer's. Plus, there is some promising clinical data that suggests that reducing amyloid levels results in improved cognition. 

What's your opinion, Nipun, Mr. Neuroscientist?

My opinion is that beta-amyloid plays a causative role (along with tau) in Alzheimer's Disease, and is therefore a part of the puzzle. And, therefore, warrants further understanding.

My head is reeling, Nipun, this was supposed to be simple. Summarize this shit and let me go.

Fair enough. Here's the gist. Beta-amyloid is likely to be harmful for neurons. And, likely to be one of the underlying causes of Alzheimer's Disease. And, is therefore a target for drug therapies for treating this disorder.

Follow the blog on twitter at @AlzBlog101, and me on twitter at @NipunChopra7. Let me know what made sense/what didn't. What you liked, what you didn't. All that good stuff. Thanks for reading! Thank you to Emily Neitzel (@EmilyNeitzel) for editing this post.

*It is logically congruent that the egg came first. Because, the species from which chickens evolved, laid an egg, which was the very first chicken. Think about it. Therefore, the egg came first (because it's parent was chicken-like, but not quite a chicken).

What is Alzheimer's Disease - defining some key terms

Everyone has heard of Alzheimer's Disease. Whether it is because someone you know has suffered from it, have read about it, or are trying to impress a lady with your knowledge of The Notebook (Admit it, gentlemen, we only pretend to enjoy that movie).

But, what exactly is this disorder? We will cover the diagnoses and underlying pathology in future posts. Today, we will focus on a definition of the disease, along with explaining a few key terms that are integral to all future posts.

So, let's get to those key terms. Now, all of you fall under two categories here -- 

1. If you are a neuroscientist, or have taken graduate level biology, most of this might seem redundant to you. But, I would appreciate you reading through this any way, to help critique my explanations and analogies. 

2. If you have always wondered what these terms meant, I hope I can shine a light on their meaning.

Neuron - These are cells in the brain. They are responsible for all your emotions and your memories.  Depending on where in the brain they are located (there are different brain regions responsible for different functions) or what type of neuron is present (there are different types), they contribute to why you think - "Ryan Gosling", every time you hear the word "dreamy". Or, you scrunch your nose, every time someone brings up yogurt (seriously guys, yogurt is disgusting). Neurons are the minions that facilitate everything you consider to be a feeling or a memory. 

In a certain part of the brain, called the Hippocampus, there are neurons that allow for the formation of new memories. During Alzheimer's Disease, this is one of the first regions to be affected. What does it mean to be affected? The neurons in this brain region die. Why is this relevant? Because, unlike cells in other parts of our body, neurons do not divide. Therefore, once a neuron dies, there will not be another one to replace it. And the relevance to memory? Well, theoretically, if you've lost a neuron relevant to a memory, you've lost that memory, or the ability to make a new memory. 

If the brain is an engine, and different areas of the brain represent different engine parts, neurons are the nuts and bolts that enable everything to work. 

Receptor - A gateway for communicating with neurons. Think of the cell as a fortress. A receptor is the draw bridge which allows communication with the fortress. Either by allowing a visitor in, or by relaying the messages of the visitor to the people inside the fortress.

Dementia - This is a loose term that is often misinterpreted. Dementia refers to a state in which normal brain function is impaired. Memory loss (as seen in Alzheimer's) is a subtype of dementia. Alzheimer's Disease represents the most common form of dementia in the adult population.

Memory - What is a memory? The ability to recall something. How are memories made? Well, we have a pretty good idea of the mechanism and brain regions involved. Where are memories stored? We know certain brain regions are important for making memories vs storing memories. Where is the memory of the lyrics to Taylor Swift's album stored? We could figure out the general area by hooking you up to a fancy machine, but here the pictures gets hairy. Suffice to say, memory formation/retrieval/consolidation/storage remain one of the key areas of research in neuroscience. What we do know is that Alzheimer's Disease involves impairment of memory processes.

Neurodegeneration - a process during which neurons progressively continue to die. Much like the progressive collapse of well-set dominoes, once this process starts, neurons continue to die over time, and there is very little (currently) we can do about it. What starts neurodegeneration in Alzheimer's Disease (Or, using our analogy, what pushes the very first domino?) ? We will visit this controversial question in future posts.

So, what is Alzheimer's Disease?

This disease, first characterized by Alois Alzheimer (hence the name) is a disorder in which neurons in key brain regions die. This results in the initial symptoms of memory loss and eventual death. Interestingly, patients of Alzheimer's Disease do not die of the disorder, per se, but it is usually the diseases associated with Alzheimer's (Pneumonia, for example) which is the direct cause of death. 

Alzheimer's Disease is an incredibly prevalent form of dementia in the elderly. And, as our sanitation, medication and standard-of-living continue to improve, the number of people suffering from it is only expected to increase. 

Please let me know if there are specific areas you would like for me to cover. You can reach out to me on twitter at @NipunChopra7.