Untangling the Spread of Alzheimer's

06 February 2012


In this NewsFlash - we find out how regions of the brain may "catch" Alzheimer's from each other, discover a new microscopy technique that can open a window on the brain in action and talk to the Australian ecologist who thinks more introduced species, including elephants, could stabilise the Aussie ecosystem.

In this episode

Tangled insoluble tau protein

00:17 - Untangling how Alzheimer's spreads through the brain

Scientists at Columbia University in New York have figured out how one of the key proteins involved in Alzheimer’s disease spreads through the brain.

Untangling how Alzheimer's spreads through the brain

Scientists at Columbia University in New York have figured out how one of the key proteins involved in Alzheimer's disease spreads through the brain.

Alzheimer's disease is a degenerative condition of the brain, caused when specific proteins in the nerve cells, known as beta amyloid and tau proteins, stop performing their proper roles in the nerve cells and instead clump into beta amyloid plaques or tau protein tangles. The tangles formed by the tau proteins were what the researchers at Columbia focussed on.

Post-mortem studies of human patients with Alzheimer's disease had suggested that an area of the brain just behind the ears, known as the entorhinal cortex, might be the starting point for the tauopathy - the degeneration caused by the abnormal tau proteins tangling up. So the researchers set out to engineer mice that would produce the abnormal human tau proteins in their entorhinal cortex, so that they could follow the progress of the disease.Alzheimers Neurofibrillary tangle

They stained sections of the brains of these mice at different ages to look at where the tau proteins were, and whether they were normal or abnormal. And their results backed up the autopsy studies done in humans - it does appear that the tau proteins spread out from the entorhinal cortex, rather than it being a case of abnormal tau developing independently in separate parts of the brain.

One of the authors of the study, Karen Duff, believes there are several take home messages from their study, published in PLoS One, one of which is that we now have a reliable mouse model that can be used to study the disease further. Another is the rather unusual discovery about the movement of the tau proteins themselves...

'By the way that we looked at these mice we were able to say the tau had left one cell and moved to another cell and that's a radical piece of biology. It's suggestive of prion diseases like mad cow disease where you get a transmission of this abnormal protein through the brain.'

And when this abnormal tau spreads through the brain, it stimulates perfectly normal tau proteins in other cells to switch to being abnormal and start to tangle up. Karen was keen to stress that although these proteins move through the brain in this way, Alzheimer's isn't 'catching' - you can't 'catch' it from someone else.

And although Karen doesn't know exactly how the tangles move through the brain, the final take home message of the study was that it could point the way towards new therapies...

'At the earliest sages of Alzheimer's when the tangles are centred in the entorhinal cortex, when tau is seen there, patients tend not to be demented. So the idea is that if we can identify the disease at that stage and start giving some therapies, we might be able to trap the disease at that stage and stop people fom becoming demented. There are a couple of approaches, but the most targeted approach would be immunotherapy, where you use antibodies to latch onto the specific protein you want to remove and it removes it by a cellular clearance mechanism. You can develop those antibodies to the abnormal tau and perhaps catch the tau as it's outside the cell in the extracellular space.'

And the use of the immunotherapy that Karen mentioned is already being tested, so it represents a positive step forward towards treating Alzheimer's.

04:06 - Super Microscope Watches Living Brain Cells

A clever “super-resolution” microscope has allowed researchers to observe changes in a single neuron in the brain of a live mouse. The exceptional level of detail even showed protrusions called dendritic spines moving and changing shape...

Super Microscope Watches Living Brain Cells

A clever "superresolution" microscope has allowed researchers to observe changes in a single neuron in the brain of a live mouse.  The exceptional level of detail even showed protrusions called dendritic spines moving and changing shape.

The best way to learn about cells is to observe  them in context in a living animal.  To do so obviously requires a high resolution microscope, but even the best optical microscopes cannot discern features smaller than around 200-300 nanometres, half the wavelength of visible light.  To go further and see smaller features involves using an electron microscope, for which the materials need to be prepared by freezing, staining or coating, so cannot be used with living tissue in vivo.

Nerve_cellsSebastian Berning and colleagues at the Max Plank Institute for Biophysical Chemistry got around this optical limit by developing a type of Stimulated Emission Depletion, or STED microscopy.  This relies on the cells containing a fluorescent dye that can be excited by absorbing certain frequencies of light, but also "de-excited" using other frequencies.  By using lasers of different frequencies and varying the intensity across a sample, STEM microscopes are able to only excite a tiny portion of the field of view, effectively increasing the sensitivity from a minimum of 200nm down to less than 70nm across.

Berning and colleagues then pointed their STEM microscope at the brains of mice genetically engineered to express Enhanced Yellow Fluorescent Protein (EYFP) in their neurons.  Employing a glass window in the skull, they were able to observe live, healthy neurons in situ.  By taking images every few minutes, they were able to see dendritic spines moving and changing shape.  As these are small processes that stick out of neurons, and are involved in receiving signals from other cells, understanding these could help us to get to grips with how the brain grows and develops, as well as changes over time.

06:47 - Elephants in the Outback

Introducing new species has proved disasterous for the Australian ecosystem. So it's no wonder that ecologist David Bowman has met controversy with his suggestion that, to stablise the system, we may need to introduce even more...

Elephants in the Outback
David Bowman, University of Tasmania

Sarah -   Since humans first set foot in Australia, 50,000 years ago, we've pretty much spelled disaster for the continent.  The first settlers wiped out the continent's megafauna, including species of giant kangaroo, and the early English colonists introduced foxes, cats, camels, rodents, rabbits, and even poisonous cane toads, and rampant African grasses - all of which had a devastating effect on the ecology of the country and have driven many of the native species to extinction.  So, when an Australian Professor of ecology published a paper suggesting that the answer might actually be to accept that we're never going to return Australia to how it once was and to introduce even more non-native species including elephants to at least stabilise the status quo, it was bound to be controversial.  Chris Smith spoke to the author of that paper, the University of Tasmania's David Bowman...

ElephantsDavid -   I've recently published a paper in Nature which is a very controversial opinion piece about the environmental management challenges in Australia associated with uncontrolled fires, feral animals, and how they've interacted with the unusual biogeography of the Australian continent.  We've sort of started a cake mix - we're mixing up all of these ingredients, now do we try to actually make this cake rise and work as a cake or do we just leave it as some sort of weird slurry?  Because all of the introductions which have been made and the changes to fire regimes have all been effectively accidental.  So, we already have a very mixed up ecology and the possibility of returning our ecology to anything like Captain Cook would have seen is an impossible dream given the record extinction rates which have occurred in Australia. 

We're in a real predicament and I think that the lesson is that humans have to manage nature, we're in the Anthropocene.  We can't just assume that natural systems are going to be self-righting if we've really hammered the natural systems with quite dramatic stresses and introductions.  It's very controversial thinking, but I've been living with these problems for 30 years and it was about time somebody said something.

Chris -   So what you would argue is that in the past, these introductions and these things have been either mistakes or ill-conceived.  But actually, if we use our brains now and start making changes which are based on science and clear evidence, then we could actually work with the problem we've got to help to resolve it and arrive at a better outcome than if we just let things go and try and conserve the status quo, because the status quo is an unstable one.

Yalgoo shire boundary on the Great Northern Highway Near Mt Gibson.David -   I think that's the key point.  We've moved on and obviously as ecologists, we have much greater understanding of the need for stabilising food webs and the impact of trophic cascades - when you disrupt food chains and how that can actually result in dramatic landscape scale changes.  All of this thinking is really ripe to trialling things because what we should be striving to do in Australia is forget about the extermination paradigm and "return Australia to its 1788 Captain Cook status", and more to manage impacts and reduce the impacts of these "threatening processes".  Through that, with that human engagement and possibly using some animals as ecological machines to achieve certain outcomes, we can basically steer or stabilise our systems way better than if we just let nature take its course.

Chris -   How has this gone down with the Australian public?  If you talk to people in Australia, they have been very heavily educated about the impact that introductions and feral animals have had on Australian ecology and for an Australian ecologist to then turn around and say, "We need actually to do this more," they must have quite a strong reaction to that, don't they?

David -   Yeah, it's very interesting.  Amongst my colleagues, I've been very pleasantly and warmly surprised by the "elephants, a crazy idea but wow!  Isn't it great?" response.  The people are putting all of the options on the table and stiring up this debate, so a lot of support.  Amongst the media, it's a little bit polarised between people just treating it as an absurd joke, who laugh or others who say "yeah, that's a big idea -  how do we control some things which are uncontrolled if our plan A approaches aren't working?"  Because we're about to run into these problems and I think that the way to advance this is that you have lots of debates and some trials so we can start being a lot more adaptive.  We haven't even talked about climate change which is another layer on top of this horrible complex mess we're in.

Chris -   So how would you do this in a safe way so we don't see the cane toad problem all over again?

David -   Right.  Well one thing which is really important to bear in mind is that there's a global dimension.  I got a fascinating email from a game manager in Namibia pointing out that when you project at the hundred to a thousand-year perspective on Africa, it's very difficult to see a future for a lot of animals.  Just the sheer environmental changes driven by people pressure.  Here, we've got a low population density in Australia, we could have game parks.  A lot of Australians think that's repugnant, but a cattle farm is okay.  But how would we do it?  Of course, we'd have to trial things and we'd have to invest money.  I would like to see somebody work through the calculation of saying, "Well let's look at all of the available options and a few crazy options to control this out-of-control grass.  Let's look at it all and let's cost them with the knowledge we've got available and start a genuine engagement".   At the moment, all that's happening is that people are saying, "This is a very bad weed" but in a holistic sense, nobody is doing anything.  I would call that an out of control situation and you know, I'm certain that there are solutions to stabilise this, but I'm not quite certain how to do it.

13:47 - Untangling the Spread of Alzheimer's

In this NewsFlash - How regions of the brain may “catch” Alzheimer’s from each other, why a new microscopy technique can open a window on the brain in action and why one ecologist thinks more introduced species, including elephants, could stabilise the Australian ecosystem!

Untangling the Spread of Alzheimer's

In this NewsFlash - we find out how regions of the brain may "catch" Alzheimer's from each other, discover a new microscopy technique that can open a window on the brain in action and talk to the Australian ecologist who thinks more introduced species, including elephants, could stabilise the Aussie ecosystem.


16:37 - Eavesdropping with Electrodes, Predicting an Eruption and muscle repair with a massage!

How scientists are eavesdropping using electrodes, predicting eruptions using magma, healing wounds with honey and massaging away your aches and pains...

Eavesdropping with Electrodes, Predicting an Eruption and muscle repair with a massage!
Brian Pasley, University of California, Berkeley; Tim Druitt, Blaise Pascal University; Sarah Maddocks, University of Cardiff; Mark Tornopolsky, McMaster University

Eavesdropping with Electrodes

The conversations we hear, and even the ones we have in our own head, have been
decoded by scientists at the University of California, Berkeley.

Activity in an auditory region of the brain called the superior temporal gyrus was recorded by implanting grids of more than 30 electrodes in 15 volunteers as they listened to various words and sentences.  The researchers, led by Brian Pasley, could then use the observed patterns of brain activity to predict what the volunteers had heard...

Brian -  Different brain sites were representing different frequencies and we could use that understanding of the relationship between the sound frequencies and the brain activity to try to predict what the sound was that the person was listening to.  One potential application is, is this perception process similar to internally verbalising or imagining speech?  Could it be applied to development of different neuroprosthetic devices for communication for example in patients who are severely disabled or have severe paralysis that have no other means of communication?

---Predicting Eruptions of Calderas

Caldera eruptions could be predicted many years in advance by regularly
monitoring the composition of magma found below.

Calderas are one of the Santorini from the edgelargest types of volcano known.  They can remain dormant for hundreds of thousands of years but have the potential to become active, releasing so much magma in the process that the surface of the Earth caves in.

Analysing samples of pumice from Santorini in Greece, providing records of magma activity in the build up to Santorini's eruption in the late 1600's, Tim Druitt from Blaise Pascal University discovered the presence of rock crystals that only form in the decades leading up to an eruption...

Tim -  There was this long period of dormancy before, many thousands of years, and yet suddenly, something happens to form all these crystals.  The processes that were priming this volcano for this big eruption actually occurred in a very short time scale, and it really would be sensible to monitor these better to improve our chances of picking up the re-awakening of these systems.

---The Sweet way to keep bacteria at Bay

Honey could hold the key to keeping wound infections at bay.

Wound infections can often be hard to treat because bacteria form a defensive barrier known as a biofilm, which can impede the ability of antibiotics to access the affected area.

Now a team at the
University of Cardiff led by Sarah Maddockshave shown, in a culture dish, that medical-grade manuka honey can dismantle these biofilms, making wounds caused by common bacteria like streptococcus pyogenes easier to treat...

Sarah  -  If you apply honey whilst your growing the biofilms, you get a statistically significant reduction in the amount of biofilm that grows which suggests that it would be a useful prophylactic treatment.  But we also found that if we grew the biofilms to 24 hours and then treated them for 2 hours with the manuka honey, we could get a total reduction in the biofilm biomass of about 85%.

---Massaging your Aches and Pains Away

And finally, a massage could speed up muscle repair and recovery after injury.massage

Whilst massages have long been used in physical rehabilitation, the mechanisms behind their beneficial effects were unknown.

Now, performing massage therapy on male volunteers after heavy exercise and analysing muscle biopsies,  Mark Tornopolsky and colleagues from McMaster University found that just 10 minutes of massage resulted in reduced inflammation and increased production of structures called mitochondria which give cells energy...

Mark -  It certainly is very encouraging that we can reduce inflammation which might help someone to recover faster and get on to their next training bout and we know from many studies that endurance exercise and having greater mitochondrial capacity is a good thing and can reduce the incidence of diabetes, obesity, and improve muscle function in older adults.  So I think anything that enhances mitochondrial function is likely to have significant clinical benefits.

And this work was published this week in the journal
Science Translational Medicine.


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