Aducanumab update

Recent work (Sevigny et al (2016)) has been making the rounds on social media. I have seen exaggerated headlines such as "New drug that halts mental decline.." and "A cure for Alzheimer's" making the rounds.

So, what's the dealio, yo? Have we done it? Have we cured Alzheimer's? Let's get into the facts here ---

1. What's this drug called?
Aducanumab - it's marketed by Biogen.

2. How does it work?
This is a drug that targets aggregated beta-amyloid. (Click here for my review on amyloid).

3. How is it different from other drugs that have been tried?
Well, for one, it isn't a "drug" per se. It is an antibody which targets the aggregated beta-amyloid.

4. What's an antibody?
An antibody is something all our immune systems generate to fight off infection. Think of it as your Superman to a Lex Luther. An antibody's role is to identify bad stuff, bind to it, and neutralize it's threat.

Up, up and antibodyyyyy (I'll show myself out)

5. Okay, so what did the study find?

The study found that in one year, patients who were given aducanumab showed less of the amyloid burden than placebo (not given the antibody). And, rather excitingly, this was a dose-dependent effect.

6. What's a dose-dependent effect?

It's a fancy way of saying, the greater the amount of aducanumab given, the better the patients seemed to do.

7. What did they measure?

They looked at amyloid in the brain as well as behavioral symptoms. Both improved dose-dependently with aducanumab.

8. Does this mean anyone suffering from Alzheimer's would benefit from this drug?

Not quite. The effects seemed most pronounced in those who were in early stages of AD?

9. Is this a cure for AD?

Too early to say. The sample size of this drug trial was small. Biogen is currently conducting Phase III drug trials (~1500 patients). Those results will become available in 2021. Also, important to note that the effect was in early stages of AD. 

10. Why the hesitation, bro?

We have been here before. other drugs showed promise in Phase I/II trials only to show no effect in larger trials. Also, don't call me bro, bro.

11. So what's the takeaway?

Very promising data. But, if someone tells you that "they found a cure for Alzheimer's", tell them that statement is still premature.

CTE in a soccer player with no history of concussion

Football/Soccer/Scientist friends,

This is a landmark study (see Grinberg et al. (2016). It shows the confirmation of chronic traumatic encephalopathy (CTE) in the post-mortem brain of a soccer player WITHOUT any history of concussion. By the way, the player (though he isn't named) is almost certainly Hilderado Bellini - a legend of the game. Bellini won the world cup with Brazil and played for some of the premier Brazilian clubs of his time.

The no-history of concussion is important, b/c it supports the idea that subconcussive impacts in soccer may be sufficient to produce CTE. And, honestly, as an aficionado of the beautiful game, this is somewhat troubling.

Why is it troubling? Because for the longest time, I (and many) assumed that CTE would rear it's ugly head in the world of soccer, and while there have been some reports of possible CTE in soccer players (see Hales et al. (2014) , this is the first (to my knowledge) which highlights the history of no-concussion.

There are caveats to over-interpreting this study-

1. This gentleman was playing soccer in the 50s - a time where diagnosing concussions wasn't the norm. Therefore, it is entirely possible that he did experience concussions - but were never diagnosed.

2. This is one anecdotal report. It's possible that his CTE is independent of his history as a soccer player and that his CTE was consequential of some other genetic/environmental effect.

Why is this study relevant to soccer?
Subconcussive injuries are asymptomatic. Therefore, they pose a greater risk to athletes than concussions because they are impossible to diagnose. If the link between subconcussive injuries and soccer is confirmed, perhaps we need to have a serious discussion about heading.

Do we know for sure that heading leads to subconcussive injuries?
No, far from it. There's little evidence for it, except this one study that suggests that heading in amateur soccer players leads to abnormal white matter (the stuff that allows brain cells to send messages to each other) restructuring ( see Lipton et al. (2013)). But, this is far from confirmation of the above.

It is interesting to note that Bellini was a central defender - a position which involves the most heading in a game (I don't have data to support this, but, it would be fairly obvious to anyone that plays/watches soccer). Therefore, the repeated subconcussive injury issue is consistent with what we might expect.

As more and more soccer players donate their brains to science, I expect us to see an increase in CTE diagnosis. With the suicides of Robert Enke and Gary Speed - two well known, high profile, footballers, the interest in CTE was always going to rise.

I'm not sure what the long-term impact will be on soccer. But, we are at the beginning stages of raising awareness for what might be an insidious beast preying upon our beloved soccer-playing heroes.

Pubmed link: Link to original study

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.