Updated: Jul 25, 2020


Alzheimer’s disease - A term we hear more and more often in our ever-ageing population. The memory-stealing, personality-altering condition affects millions of people across the globe mainly in the later stages of life and although the condition is common, we still do not know what causes Alzheimer’s in over 99% of cases. Could the disease be caused by lifestyle choices? Could we warn of neurodegeneration if we smoke less and exercise more? What about susceptibilities in an individual's personal genetic code? Could one mutated gene trigger a cascade of untoward events in the brain? Another much scarier mechanism flung around the news recently was Alzheimer’s could potentially be ‘transmitted’ - a word nobody wants to hear when linked with a currently incurable disease.

‘Contagious’ Neurodegeneration: Prion Diseases

I have been asked several times by people curious in my work if it is possible to ‘catch’ Alzheimer’s disease. And my response has always been a firm no as there have been no reported cases of human-to-human transmission (passing) of Alzheimer’s. However, there is a rare class of neurodegenerative conditions which can be transmitted called Prion diseases. Such diseases are caused by Prions; an abnormal variant of a protein found on the surface of every neuron in a healthy mammalian brain. Unlike a typical virus which injects its unwanted DNA into human cells in order to replicate, rogue prions are able to transform normal prion proteins into fellow rogue prions by altering their shape. This allows the rogue prions to spread throughout the brain, which leads to widespread neuron death and brain tissue loss.

Contracting a prion disease is much rarer than the catching a virus through a cough or splutter as transmission is thought to require direct ingestion, injection or insertion of the rogue prion into an individual. A famous case of prion disease was the BSE crisis in the 1980s/1990s; where almost 200 individuals in the UK died of a prion disease called variant Creutzfeldt Jakob Disease (CJD) after eating beef contaminated with cattle prions. Another incidence of prion transmission came from young individuals of short-stature being injected with inadequately-purified growth hormone isolated from the pituitary glands of cadavers, failing to remove all rogue prions and leading to cases of iatrogenic CJD (iCJD). Also, it has been noted abnormal prions can stick to metal neurosurgical tools, meaning extensive sterilisation must be undertaken following brain surgery. In spite of prion diseases hitting headlines for their infectious nature, there are an array of other prion diseases which are not contracted due to transmission. These can occur due to familial inheritance of prion gene mutations or randomly, much like the majority of Alzheimer’s cases.

Research paper: An example of amyloid seeding in humans?

The majority of neurodegenerative diseases are characterised by misfolded protein aggregates in the brain at post-mortem, with Alzheimer’s patients all having misfolded amyloid-beta and tau in their cerebrum. It has been hypothesised that as these pathologies are both formed of misfolded versions of resident brain proteins, they might possess similar properties to prions such as the ability to 'seed' in the brain. Many mouse models have been used to explore this theory over the past decade, with results looking like both rogue proteins can induce pathology following injection. But a real human insight came from the study of the brains of a cohort of patients who had succumbed to iCJD following injection of contaminated growth hormone. Although all patient brain tissue had hallmarks of prion diseases, some of these individuals also had amyloid plaques; the supposed first sign of Alzheimer’s; in the brain and blood vessels. As it is unusual to see amyloid pathology in such young individuals, the hypothesis was formed that the growth hormone vials derived from human pituitary glands were also contaminated with amyloid seeds, which had lead to the formation of amyloid plaques in the brain.

Researchers at University College London (UCL) accessed the exact growth hormone vials used to inoculate patients in the 1950s-1980s and inoculated the material into mice which form amyloid plaques with age. The researchers wanted to test if the growth hormone material would increase the number of amyloid plaques following a set incubation period, which would argue amyloid seeds are present in the growth hormone vial. After an 8 month incubation, the mice injected with material from the suspected amyloid-contaminated vials of growth hormone material did experience an increase the level of amyloid plaques in the brain compared to suspected non-amyloid containing vials, synthetic growth hormone and sham-inoculated controls. These amyloid plaques were also seen deposited in blood vessels; the hallmark of a disease called cerebral amyloid angiopathy (CAA), which can cause vessel blockages and strokes. The study concluded the likely reason for the iCJD patients harbouring amyloid plaques was due to the inoculation of amyloid seeds with the growth hormone preparation, and CAA can now be classified as an iatrogenic disease.

Does this mean Alzheimer’s is transmissible?

While the implications of this study can be stretched by the media, one point is clear: Alzheimers disease was not transmitted in these mice - amyloid was, and we are still unsure of the exact role amyloid plays in the mechanism of neurodegeneration. There are a cohort of healthy older people who die with high levels of amyloid and no signs of Alzheimer’s disease, providing an argument amyloid burden can exist without neuron death. Also, no comments were made on other features necessary to diagnose Alzheimer’s in these mice, such as tau pathology and neuron death; with the former also not being noted in the iCJD patients.

But could these individual’s brains have gone on to develop early Alzheimer’s disease if iCJD hadn’t taken hold? Confirming this theory would require a case of a growth hormone-treated individual with Alzheimer’s disease, none of which have obviously presented yet. What this study does highlight is amyloid is potentially able to seed in humans, therefore the need to fully comply with approved sterilisation techniques for neurosurgical tools to ensure the removal of prions and amyloid is of the upmost importance.

Alzheimer’s disease still cannot be described as infectious akin to prion disease or transmissible, but this study hints amyloid pathology could be seeded in humans under extremely rare circumstances which should not arise any more due to safety procedures. And what this means for contracting the disease is still unclear as the mechanism of Alzheimer’s disease are still under investigation.

What did you think of this study? Let me know on my social media pages!

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Paper: Purro et al (2018). Transmission of amyloid-β protein pathology from cadaveric pituitary growth hormone. Nature 564, 415-419

For some sciencey reads on this topic, click the links below

A scientific review of Prion diseases

Neurodegenerative diseases: expanding the prion concept

Amyloid beta as a Prion: Review


Updated: Jul 25, 2020


Could a shortage of dividing cells in the brain be a feature of Alzheimer’s disease? Recent research indicates this could be the case.

Your body is a mega-mash up of many different cell types working away at their specific jobs to keep you alive and kicking. Some of these cells are capable of dividing and producing near-identical daughter cells in a process called mitosis. For example, skin cells (aka keratinocytes) are able to divide to replace ‘old’ dead cells with fresh new ones - explaining why your summer tan fades after a few weeks of being back in grey weather (England y u like this?). Other cells in your body are not so keen on splitting apart into daughter cells and these are described as ‘post-mitotic’. Neurons, one of the major cells types of the brain, do not divide, meaning the key communicators of the central nervous system aren’t so easily replaced if they are lost. Conditions which cause the death of neurons, such as Alzheimer’s disease, are normally irreversible and notoriously difficult to treat.

New year, New Neurons: Neurogenesis in the Adult Brain

Although neurons are post-mitotic, there are two known pools of neural stem cells in the adult brain. Neural stem cells can divide and produce the precursor cells which are able to mature into specific neurons throughout life. One of these pools is found in the subventricular zone of the lateral ventricle (a lahttt of words to describe a region near one of the fluid-filled holes in your brain), which is believed to give rise to inhibitory interneurons of the olfactory bulb (your 'smell' region). The other pool is in the dentate gyrus, which forms part of the hippocampal formation; the brain region vital for generating long-term memories. The pool of neural stem cells in this region mature through several stages to become excitable dentate granular cells (DGCs).

DGCs are morphologically beaut neurons, having a small cell body from which a web of neuronal processes project. Their extensive branch-like dendrites can receive thousands of excitatory signals from the entorhinal cortex, a brain region proposed to integrate mounds of 'higher function' information (sensory, motor, spatial and language inputs to name a few) received in your neocortex. The DGCs process these inputs and transmit their own excitatory signals along their mossy-fibre axonal projections to the CA3 region of the hippocampus. Immature DGCs, produced during neurogenesis, are believed to be super important for learning and memory functions as they are extremely excitable, sending signals with little stimulation, and are plastic, easily altering the strength of their synaptic connections. Once DGCs become mature, they become less eager to signal to the CA3 neurons and find it more difficult to alter their synaptic strength, but when they do signal, these are believed to be in robust 'bursts'; making sure the CA3 neurons really get their message. In terms of functionality, evidence suggests DGCs at both immature and mature stages play vital roles in memory formation.

Out with the Old, No Cells for the New: Alzheimer’s disease and Neurogenesis

So whasoccurin' with these DGCs in conditions of permanent memory loss? In a recent paper published in Nature Memory, Moreno-Jimenéz et al describe the loss of numbers and lack of maturation of DGCs and their progenitors in patients with Alzheimer’s disease (AD). AD is a common, age-related neurodegenerative condition and one of the initial subsets neurons to die in a patient's brain are in the hippocampus; resulting in the progressive loss of memory. Specifically, 'ground zero' of Alzheimer's disease, describing the region first affected by neurodegeneration, is believed to be the entorhinal cortex. Therefore, DGCs in the dentate gyrus are left with reduced stimulation from entorhinal projections and eventually succumb to neurodegeneration themselves, meaning the ability to convert novel experiences into long-term memory is majorly disrupted. However, the effect Alzheimer’s disease has on the pool of neural stem cells and progenitors in this region in humans has only recently been investigated.

Moreno-Jimenéz and colleagues present data using human brain fixed tissue investigating how neural stem cells and progenitors in the dentate gyrus are affected by age and AD. The researchers revealed individuals with normal cognition have an abundant pool of neural stem cells and high numbers of neural precursors in the dentate gyrus until over 80 years of age, with age moderately reducing these numbers over time. However, in individuals with Alzheimer’s, these pools were significantly depleted irrespective of patient age. The root of this depletion was described by the lack of neural progenitor maturation with AD progression, as the numbers of immature DGCs were significantly reduced in AD brain slices. These findings suggest AD has an abnormal effect on neural stem and progenitor cells numbers which are not concurrent with normal age-related changes, and this is potentially due to problems with maturation of progenitors in the dentate gyrus.

What does this mean for disease-associated mechanisms related to AD? It is already established that AD somehow drives the death of dentate granule cells alongside other neurons in the hippocampus, but if the disease also prevents the production of replacement cells, this creates a double inhibitory effect. Maintaining the number of neural precursors and driving their maturation in AD patients may delay or prevent the onset of memory deficits in AD as these cells could replace those lost to the disease. However, it still unclear how having an abundance of healthy neural precursors in a potentially neurotoxic environment would aid patients in the long run. It will be important to establish whether AD causes or is caused by changes to DGCs maturation, which will require us to answer the big question: what causes neurons to die in AD? And unfortunately, that is still a complete mystery. But what this work shows is that there may be more to AD that just hippocampal cell death. In fact, it suggests AD could be a double hit of mature neuronal death and new neuron production disruption. Further research into the dynamics and origins of these two mechanisms could open up an interesting avenue on the road to AD therapeutics.

Main Paper: Adult hippocampal neurogenesis is abundant in neurologically healthy subjects and drops sharply in patients with Alzheimer’s disease, Moreno-Jimenéz et al (2019)

Other References used for your further reading pleaaaaasures

Neurogenesis in Adult Subventricular Zone

Adult neural stem cells in the mammalian central nervous system

Entorhinal Cortex

Mature granule cells of the dentate gyrus: passive bystanders or principal performers in hippocampal function?

Neural stem/progenitor cells in Alzheimer’s disease


Updated: Jul 25, 2020


Public speaking. Love it or loath it, it a skill the majority of us have to attempt to master at some point during our career. And with the handy aid that is Microsoft powerpoint, doing a big presentation should be as easy as pie. You have an affective side-kick who, instead of spending minutes trying to vocally or physically (chalk boards be-gone) illustrate your work, can display your data in glorious technicolour with a simple click and beautiful custom-animation 'fade'. And you know your work. You do your work every single day. You can talk about your work. So presenting your beloved project to an audience with your trusty friend powerpoint should be a doddle.

If only it were that easy...

Slideshow presentations can sometimes be more of a hinderance than a help when trying to communicate your work as there are SO many powerpoint-pitfalls: large chunks of tiny text, blurry images with no context and horrendous colour schemes to name a few (I once had a prize-winning lecturer who made white slides with yellow text... like what is that?). Even with the perfect presentation, if your chat isn't engaging, you are more than likely going to lose your audience. Normally as the presenter, you are the expert in the room about the topic of the talk. This can lead to a very easy slip into a 'verbal diarrhoea'-style rambling of complex concepts or assuming the audience knows as much as you, leaving them pining for an explanation. You have to contend with all these problems before even thinking about the nerves which accompany a solo talk in front of an audience. So how can you make sure you pull your big presentation out of the bag? Here are my top 10 tips!

1. Know your Main Message

Why are you doing this talk? What is the one thing you want the audience to remember when they leave the room? Decide on your main message before you double-click on that powerpoint icon and focus your slides around communicating this idea.

2. Make as many slides as minutes you have to present (or less)

As an audience member, there is nothing worse than seeing a 20-minute presentation speaker open a file consisting of 48 slides. Yes, some slides only require a quick click-through but if you are flicking past them, is the message of that slide really pivotal to your presentation? Normally, we underestimate how long it will take us to explain a concept, so give yourself at least 1 minute per slide. If you finish a bit shy of time, it just means more time to discuss your work with the audience and is MUCH better than running over. So a 20 minute talk should have no more than 20 slides, never 48.

3. Display only key words or sentences on slides

Your slides are their to guide your audience through your data and prompt you to remember what to say. They are not there to display huge chunks of text, even if it is the best explanation in the world. In this scenario, there are only two outcomes: your audience read the text and do not listen to you, or you end up reading out the text verbatim and the audience switch off. Both situations equal one thing = disengagement. Keep that text to a minimum and verbally communicate your fab data to the audience yourself.

4. Use images or graphics to help explain complicated ideas

Could you imagine a medical professor trying to explain the anatomy of the human body without a skeleton model or detail pictures of organ structures? It would be veryyyy wordy and veryyyy confusing. If there is a complex idea you have to get across to your audience, a visual aid can be a huge help. You can find great diagrams on the internet, or you could try to draw a simple schematic using powerpoint or illustrator. Then you and your laser pointer can hold the audiences hand and walk them through even the most complicated of scenarios step by step.

5. Keep your explanations simple

Yes, the data in this one graph may have taken you days to collect and hours of tweaking assay conditions, but the audience do not need to know all of that. And if you tell them, you are at risk of losing their attention. It is easy when nervous to start just talking but collect your thoughts, breathe and explain your data in a few sentences; keeping that 'main message' in mind.

6. Hydrate with water and coffee

... or any of your other favourite drinks. For a 30 minute talk, you are likely to sink hours into making slides and prepping your talk so keep hydrated. It is amazing how much we forget to drink when we are busy, so having a big glass of water can really open your eyes to something you have missed out or that would-be-embarrassing typo. If you have left making your slides until the day before, most likely caffeination is the only answer.

7. Practice your presentation out loud

Have you ever had that experience when you have written a word down hundreds of times but never said it out loud? And when you do try to say it, you can't quite get your tongue around it? Well, you definitely do not want that experience while presenting in front of an audience. You may have an idea in your head about what you want to say but just sit with your slides and speak through what you'd like to say on the day. You will find there is a concept which is a bit tricky to explain, or a word you stumble over, so you can work on ironing these problems out. Plus, if you have stood up and said the talk before, it is much easier to do again, even if this time there are people listening.

8. Speak S-L-O-W-L-Y

When you are nervous, your mind starts to race, you might feel a bit hot under the collar and your heart pumps that little bit faster. This is due to the release of adrenaline (see my blog post on stress for the science of this mechanism!) and your speech can also fall victim to adrenaline's functions. You may feel like you are talking at a normal pace but to the audience, you are racing through your introduction quicker than Usain's 100 metres. Take. It. Sloooowwwww. Make natural pauses in between phrases and emphasise words to keep your speech at a normal pace. In your head, you may feel like a tortoise but to the listeners, you sound normal and not nervous at all. Plus, speaking slow gives you time to think about what to say next.

9. Chat through your presentation with a friend in a relaxed environment

There is nothing more soothing that chatting with a friend over a glass of wine. So why not try to explain your up coming presentation to them? This can be a friend in your field or someone completely blind to your work, but either way, speaking to them will help you point out concepts which might be sticky to communicate to your audience and tests you on your own knowledge. Plus it makes your data seem less scary when talking about it to a friendly face. Another tip: get your friend to ask you questions as you go through as they may have some similar thoughts to your future audience.

10. Enjoy presenting your work!

This is the most important thing. You have worked so hard. Not just on this presentation but in general, day in day out, on your project. And now is your chance to share that work with other people. It is not often you get the attention of lots of experienced individuals, so your talk should be viewed as an opportunity to get open and constructive feedback, as well as praise and congratulations. You know your stuff so show it off!

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I hope these tips give you a guide to puttin together a killer slideshow and some reassurance if you are feeling worried about an upcoming presentation. Just remember that you are the expert of your work; no one in that room knows more about your topic than you. So relax, smile, speak out and enjoy sharing your amazing work!


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