A Cause of Alzheimer’s? Part 1- Biofilms

Image: Pixabay

(This material connects to what I discussed in episode 1- Biofilms)

Biofilms- aggregates of material in which bacteria are encased and grow– are relevant structures to fields such as medicine and dentistry, as I mentioned in episode 1. However, when I discussed them back in October 2020, I specifically mentioned their relevance to disease. So, today I thought I’d elaborate a bit and discuss a specific example that is at the forefront of modern research. Specifically, we’re going to talk about Alzheimer’s.

This connection between biofilms and Alzheimer’s is made in a 2020 review paper published in the Clinical Microbiology Newsletter. Although there are other ways of phrasing it, I thought it would be easiest to describe the theory in sequence, starting with infection and ending with the symptoms of Alzheimer’s itself.

So, what happens after biofilm-capable bacteria invade the bloodstream? Bacteria in the mouth have the capacity to form biofilms- to the great frustration of dentists everywhere. It is possible that biofilm fragments of around 100 to 1000 cells, complete with extracellular matrix, can become dislodged, enter the bloodstream and become coated with immune system components. Ordinarily, liver cells called ‘Kupffer cells’- which are capable of phagocytosis- are able to deal with these ‘proto-biofilms’ once they reach the liver. However, if a fragment has all the protective abilities of a biofilm, these Kupffer cells might not be able to digest them. In this case, the fragments can end up in the arterial system. As the aorta pumps oxygenated blood from the heart to the rest of the body, you can imagine that this is a problem.

And this is where genetics and other host factors come into the equation. Ideally speaking, the blood-brain barrier (BBB) should not be permeable enough for these fragments to enter into the brain. However, if the immune system of the host is impaired for whatever reason, such as in the case of diabetes or as a result of normal aging, these biofilm fragments might be able to enter the brain.

This becomes a problem if the biofilm is able to establish itself on the tissues of the brain. In order to obtain nutrients and prevent the host healing, the biofilm provokes constant inflammation, as evidenced by two to three orders of magnitude more interleukins and far more neutrophil immune cells than you would expect. In essence, the biofilm hijacks the immune system to create this inflammation.

There are different host reactions to this chronic inflammation, but the most relevant for our purposes is the formation of amyloid- the formation of large aggregates of amyloid protein in the extracellular space. These amyloid plaques are then supposed to be responsible for the so-called ‘tauopathies’ which are classically associated with the pathology of Alzheimer’s.

Now, it’s important to realise that there is no consensus about what causes Alzheimer’s. For all we know, the biofilm-involved mechanism might not be the ultimate cause. As I highlighted with the possibility that amyloid plaques causing tauopathies, all of these factors may even connected. There are two other factors that have been suggested which I am going to cover in separate posts- a microtubule-binding protein known as tau we mentioned just now (discussed in Part 2) and the possible role of microbiome dysbiosis (in Part 3).

12- The Wnt Signalling Network

Building on our discussion of both signalling pathways and G-protein coupled receptors from a few weeks ago, this week we’re going to discuss the Wnt signalling pathway- a pathway which is crucial in aspects of development and can have widespread impacts on the cell. It all sounds rather intimidating, but there’s actually surprisingly few steps involved in this pathway- and we’re only going to be focusing on one part of the signalling network, which makes life a lot less complicated!

Sources for this episode: 1) Alberts, Johnson, Lewis, Raff, Roberts, and Walter (2008), Molecular Biology of the Cell, Fifth Edition, p.948- 950. Abingdon: Garland Science, ‘Taylor and Francis Group LLC’ 2) National Center for Biotechnology Information (2020). PubChem Compound Summary for CID 445638, Palmitoleic acid. Retrieved November 29, 2020 from https://pubchem.ncbi.nlm.nih.gov/compound/Palmitoleic-acid 3) Janda, C. Y., Waghray, D., Levin, A. M., Thomas, C. and Garcia, K. C. (2012), Structural basis of Wnt recognition by Frizzled. Science 337: 59- 63.

An introduction to the website

Hello everyone and welcome to Biopedia! This is just a quick introduction to say what this website is and will be included it in. To those who have found this website through my podcast- welcome back! To those of you who have found us through some other means- welcome! Feel free to explore the Biopedia podcast as well- there will be a link to it in the ‘Where to Find Us’ section in the website details. Alternatively, you can listen to all my previous episodes on the ‘Podcast’ section of the website.

Biopedia is primarily going to be a hosting platform for my podcast of the same name, as you might expect. As such, I’ve set it up so that both old and new episodes will appear on the website, along with the references and show notes that would ordinarily be included in the description of a new episode.

From time to time, I will add posts to the ‘Blog’ page of the website in addition to the regular episodes. This will either be new content that I haven’t been able to put into an episode yet, or an expansion on a subject that has recently been in an episode for which I have subsequently discovered something new. Where applicable, sources will be included at the end of the post.

Unfortunately, I might have to ask you to bear with me to some extent- although I do have experience with WordPress, I worked with it in a different capacity and format. This means there will be a teething period as the website is set up, during which I will have to find my way around. We will get there, but it may take a little longer than I would have liked.

So, that’s it for now. Hopefully, the site will be set up properly and running smoothly soon. For any questions, comments or indeed suggestions for future episode topics, we can be contacted at ‘biopediapodcast@gmail.com’. Until next time, have a great week!

11- Rewind: Cell Theory

In the first of our ‘Rewind’ episodes, we go back to basics and discuss cells- where they came from and the famous cell theory of 1839, which is still present in textbooks today. There are more stories than we can cover which lead up to cell theory, so just see this as an introductory episode until when and if we can come back to these famous names and discoveries.

Sources for this episode: 1) Author unknown, National Geographic, date unknown, Cell Theory (Encyclopaedic entry, online). 2) Silver (1987), Virchow, the Heroic Health Model in Medicine: Health Policy by Accolade. AJPH 77(1): 82- 88 (p.86 for the discussion of Remak).

Please note: at 02:29 I mention that the postulates were ‘released’. I am not sure if this is the right word to use, but I am still looking into this, so watch this space for now.

10- The Lamellipodium

As discussed in previous episodes, the actin cytoskeleton is vital to allow cells to move. But what about the specifics? In this episode, we’re going to be dissecting the lamellipodium- a meshwork actin structure that some cells use to move.

Sources for this episode: 1) Alberts, Johnson, Lewis, Raff, Roberts, and Walter (2008), Molecular Biology of the Cell, Fifth Edition. Abingdon: Garland Science, ‘Taylor and Francis Group LLC’ 2) ‘Mechanobiology Institute, Singapore’, 2013 (YouTube), Arp2/3 complex mediated actin nucleation (online) [Accessed 23/11/2020] 3) Berro, Michelot, Blanchoin, Kovar and Martiel (2007), Attachment Conditions Control Actin Filament Buckling and the Production of Forces. Biophysical Journal 92(7): 2546- 2558. 4) Kiuchi, Ohashi, Kurita and Mizuno (2007), Cofilin promotes stimulus-induced lamellipodium formation by generating an abundant supply of actin monomers. The Journal of Cell Biology 177(3): 465- 476.

9- The Platypus’ Larger Cousin

We’re all familiar with the platypus, but it still has surprises up its sleeve. On the podcast today, we get to know its bumper-sized cousin- Obdurodon tharalkooschild.

Sources for this episode: 1) Pian, R., Archer, M. And Hand, S. J. (2013), A new, giant platypus, Obdurodon tharalkooschild, sp. nov. (Monotremata, Ornithorhynchidae), from the Riversleigh, World Heritage Area, Australia. Journal of Vertebrate Paleontology 33(6): 1255- 1259. 2)Dell’Amore, C., National Geographic (2013), Giant Platypus Found, Shakes Up Evolutionary Tree (online) [Accessed 17/11/2020, 11:36 am].

8- Orca Population History

Killer whales are an icon of the world’s oceans. However, genetic studies show that they haven’t always been doing so well- especially during the last Ice Age. What’s the story? And what relevance does the millennia-old plight of the orca have today? On the podcast today, we’re going to use a genetic study from 2014 to explore just that.

Sources for this episode: 1) Moura, A. E. et al (2014), Killer Whale Nuclear Genome and mtDNA Reveal Widespread Population Bottleneck during the Last Glacial Maximum. Molecular Biology and Evolution 31(5): 1121- 1131. 2) General dates for some of the geological epochs discussed are widely available and can be found at sources such as Wikipedia.

A small housekeeping note: the lamellipodium episode is taking longer than expected and so has had to be pushed back a bit until November 25th (episode 10).

7- Localised mRNA and Cell Polarity

On the podcast today, we cover the concept of localised mRNA, which can be relevant to cell polarity.

Source for this episode: 1) Martin, K. C. And Ephrussi, A. (2009), mRNA Localisation: Gene Expression in the Spatial Dimension. Cell 136: 719- 730.

6- Persister Cells

Antibiotic resistance we’ve all heard of by now, but what about antibiotic persistence? Join us as we explore the phenomenon of persistence, which allows bacterial infections to reappear even after antibiotic treatment. And all while being genetically identical to their susceptible neighbours!

Sources: 1) Wiley, J. M., Sherwood, L. M. and Woolverton, C. J. (2017), Prescott’s microbiology, 10th edition (International Edition), New York, McGraw-Hill Education, p.150, p.188. 2) Fisher, R. A., Gollan, B. and Helanie, S. (2017), Persistent bacterial infections and persister cells. Nature Reviews Microbiology 15: 453- 464. 3) Balaban, N. Q., Helanie, S., Lewis, K., Ackermann, M., Aldridge, B., Andersson, D. I., Brynildsen, M. P., Bumann, D., Camilli, A., Collins, J. J., Dehio, C., Fortune, S., Ghigo, J.-M., Hardt, W.-D., Harms, A., Heinemann, M., Hung, D. T., Jenal, U., Levin, B. R., Michiels, J., Storz, G., Tan, M.-W., Tenson, T., Van Melderen, L., Zinkernagel, A. (2019), Definitions and guidelines for research on antibiotic persistence. Nature Reviews 17: 441- 448. 3) Some of this discussion is also based on my prior education on the topic.

5- A Projected Range Shift during Global Warming

It is common knowledge that bees as a whole are declining as a result of climate change. But what about individual species? On the podcast today, we cover a 2019 paper which predicted that the Australian small carpenter bee, Ceratina australensis, might go against this trend….

Source for this episode: 1) Dew, R. N., Silva, D. P. And Rehan, S. M. (2019), Range expansion of an already widespread bee under climate change. Global Ecology and Conservation 17 (2019): e00584.