IOS Extra: Big Bang & Alzheimer's

What existed before the Big Bang? Can the brains of young people tell us anything about Alzheimer’s?

These were the topics discussed in the fourth edition of our regular series of science podcasts, Inside Oxford Science: you can listen here or download it from iTunesU.

In OxSciBlog’s Inside Oxford Science Extra (IOS Extra) we delve deeper into the issues behind the podcast with extra info and links…

Time before time
‘Nothing’: that was the old answer you gave to the question of what happened before the Big Bang but, as Pedro Ferreira of the Department of Physics explains, physicists are now thinking again about a ‘time before time’.

But what might such a time be like? There are plenty of theories:

One idea is of a ‘Phoenix universe’ in which the universe undergoes a cycle of expansion and collapse with each new universe arising like a phoenix from the ashes of the old.

Each expansion would generate more entropy so that the universe gets bigger and bigger each time and effectively lasts forever. But not everyone likes the idea of a universe destined to collapse and shatter.

Another idea from String Theory is that there was a pre-Big Bang universe which was infinitely big, then underwent a collapse – going through a transition, a ‘haze’, during which we don’t know the laws of physics – and then emerges expanding again.

Another thought is that we actually live in a five dimensional universe – that our four dimensional universe is a ‘slice’ through this – and that our 4D universe floats around colliding with other 4D universes and that these collisions are like Big Bangs, happening again and again.

Test of a wave
One of the problems in deciding which theories are more likely is that we don’t know the physical laws that were operating ‘a few seconds’ after the Big Bang – when we say ‘Big Bang’ we’re extrapolating backwards the laws that we know now and deducing that there was an initial point - a singularity.

It could be that the fabric of space-time isn’t smooth at all, it’s full of loops and rings a bit like a rug and if you look closely it becomes very ‘rough’ and the physical laws look very different.

So how could we test these theories?

The key is to look far back in time using gravitational radiation – ripples in space-time that should preserve the ‘imprint’ of the early universe.

Over the next five years there are missions to observe these: There’s LIGO, which is looking for small-scale gravitational waves, and LISA, which might also be able to detect these. There is also the possibility of picking them out from the relic radiation from the very hot, early Universe - a host of experiments with acronyms such as QUIET, SPIDER, EBEX and even the Planck satellite are rushing ahead, trying to get the first glimpse of these elusive signals.

Unfortunately gravity waves aren’t powerful or distinct enough for us to be able to use them alone to predict which theories are correct – although they will help us to rule some out.

More work now needs to be done to narrow down which theories we should be looking to choose between.

Genes and the brain
OxSciBlog’s own Jonathan Wood then tells us about new brain imaging research from Oxford that has shown that even young people with a gene associated with higher risk of Alzheimer's disease (AD) show differences in the way their brains function decades before any symptoms might occur.

APOE is the gene in question and it’s the e4 version of this gene that’s related to an increased risk of Alzheimer’s: If you inherit one copy of APOE e4 you are maybe 3 or 4 times more likely to get Alzheimer’s. If you have two copies you are 10-12 times more likely to get it.

However if you have the e4 version, you don’t necessarily get Alzheimer’s: a more helpful way of looking at it is that in the general population, 20-25 per cent have this gene variant. Among people with Alzheimer’s, this rises towards 50 per cent.

But what does the gene do? What’s the connection?

The gene encodes a protein called apolipoprotein E. Outside of the brain it is involved in removing cholesterol from the blood and taking it to the liver for processing. In the brain itself, the protein seems to be involved in initial development, repair and remoulding the wiring of the brain.

One of the first symptoms of Alzheimer’s, of course is impaired memory. And there are known to be changes in the part of the brain called the hippocampus. Interestingly, brain scans of older people with the e4 gene show that the hippocampus is smaller and the way the brain functions is different, whether they have Alzheimer’s or not.

So Oxford researchers at the Centre for Functional Magnetic Resonance Imaging of the Brain, led by Clare MacKay, decided to look at these changes in younger people and recently published their findings in PNAS.

Early brain changes
Dr MacKay’s group did brain scans of people aged 20-35, including 18 carriers of the APOE e4 gene (with one copy) and 18 people without.

The volunteers did two tests. In the first, they just lay in the MRI machine to give a resting-state MRI scan. In the second they did a simple memory test involving images that they were shown while being scanned.

Both tests showed differences in the way the brain functioned in those with the e4 gene and those without. This was a real difference in the brain function decades before anyone would be expected to go on and develop any memory impairment, let alone Alzheimer’s. It suggests that something is changing in the brain very early in life, or even in brain development – a totally new finding.

Other tests are needed to repeat these observations, the researchers point out, and, ideally, you would do a really long-term study and follow up these volunteers over many years and see how they faired – whether there was any brain degeneration as they aged.

Still, it offers the tantalising prospect of one day being able to devise a test to distinguish very early on which people will go on to develop Alzheimer’s.

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