Alzheimer’s disease, microglia and essay writing

The Nervous System & Neurological Diseases (MEDC0012) was one of the most challenging modules of Year 2, both in terms of content and assessment. The coursework consisted of a 1500-word essay which was definitely a level up compared to Year 1. We were given the possibility to choose from a list of essay titles, so I decided to focus on the role of  microglia – the innate immune cells of the brain – in Alzheimer’s disease (AD). From the first year module “Infection, inflammation and repair” I had become fascinated by the immune system and I was eager to learn more about the pathophysiology of AD in relation to neuroinflammation.

My task

The essay  title asked

• to explain the function of TREM2 in microglia,
• to discuss how mutations of TREM2 may contribute to amyloid pathology in AD, and
• to consider to what extent this shed new insights into the causes and mechanisms of AD.

In fact, TREM2 is a receptor expressed by microglial cells which is thought to play an important role in mediating microglial interactions with the surrounding environment, regulating cell survival, phagocytosis, lipid metabolism, and more. Dysfunctional polymorphisms in TREM2 have been associated with an increased risk for AD by genome-wide association studies, making the study of this receptor a hot research topic.

The highs and lows

Considering the vastity of the subject and the strict word limit, I really appreciated the oppurtunity to submit a short essay plan: knowing that I was moving in the right direction was helpful and encouraging. While I thought I had included in my plan enough information, I actually found later on that I had to look for more references… This mistake was an important  lesson for the future: be sure to make a sufficiently detailed plan of the essay before starting to write the draft!

Indeed, structuring this essay was not so simple. The introduction was supposed to provide sufficient information to a non-expert reader. In my case, for example, it was necessary to introduce AD, explain the amyloid-cascade hypothesis as well as the function of microglial cells, before delving into the ligands, functions and variants of TREM2. The introduction was relatively straightforward, as most of the background content had been covered throughout the module. Instead, the real challenge concerned the molecular detail of the research currently carried out on TREM2 (the bulk of the essay!). This was further complicated by the fact that the role of TREM2 in AD is yet to be established. Indeed, primary research articles report contrasting information on the functions of TREM2, i.e. they show different results in a similar experimental set up (for example, mutant TREM2 in mouse models of AD has been reported to cause an increase / decrease in amyloid plaque load). Thus, a key aspect of my essay  was to give a balanced argument.

Given the extensive amount of information published on TREM2 in the past decade, my greatest struggle was identifying the most important points to include the essay. I tried to overcome this difficulty by first reading a few reviews on TREM2 and then selecting the most significant primary research articles from their references. Still, it is important to acknowledge that I have given only a brief overview of a small part of research concerning TREM2.

In conclusion…

This assessment was an occasion for me to read some basic research articles in the  neuroscience field. Although it was quite tough and at moments overwhelming, I am continuously more convinced of going into research after my studies at university.

Learning about the nervous system and neurological disorders in this module was very interesting, and I particularly enjoyed looking into one of the links between immunology and brain function with this piece of coursework. Yet, I am not planning to go down the neuroscience research pathway – I’m happy to appreciate how complicated and amazing the brain is “from a distance”!

[Unfortunately, as coming Year 2 students may choose the same essay title, it is not possible for me to share my essay]