Friday, June 17, 2016

Alzheimer's due to infections?

Hey awesomites!!!
Could Alzheimers' stem from infections?

First let's understand the normal Blood brain barrier and why does it breakdown in old age...

Normally, the barrier limits the entry of blood-derived products, pathogens, and cells into the brain.

What does the blood brain barrier formed of? 
Brain endothelial cells, perivascular mural cells, and pericytes form the BBB.

What happens in old age?
Degeneration of the cells of the barrier, mainly pericytes, which leads to leaking out of blood-derived proteins (Immunoglobulin, albumin, fibrinogen, and thrombin) most of which occurs in the hippocampus and cortex (the part of brain associated with learning and memory).
A chronic breakdown of the membrane (barrier) causes progressive neuro degeneration with loss of neurons mediated by direct neuronal toxicity, oxidative stress, and neuronal detachment from their extracellular matrix!

What is Alzheimer's disease? 
Characterised by selective neuronal vulnerability, there is breakdown of blood brain barrier in the hippocampus and its subdivisions (CA1 and Dentate Gyrus) that is worsened with mild cognitive impairment (MCI) and correlated with injury to pericytes (shown by CSF analysis).

The question now arises-
Could it be that Alzheimers' disease stems from toxic remnants of the brain's attempt to fight off infections? 
Well, the answer is Yes!
Infections that are too mild to elicit symptoms may produce a fierce reaction that leaves debris in the brain, causing Alzheimers!
But How?
A virus, fungus or a bacterium gets into the brain, passing through the blood brain barrier that becomes leaky as people age!
The brain's defense system rushes in to stop the invader by making a sticky cage of proteins- BETA AMYLOID!!! The microbe becomes trapped in the cage and dies. This forms a plaque- unique hallmark of the disease.
These proteins are part of the innate immune system, that's the body's first line of defence against infections.
Formation of tangled thread-like tau proteins kill nerve cells resulting in inflammation and then more and more of nerve cells are destroyed!

Does that mean everyone with infection develops AD?

What about people with genetic predisposition to AD?
The problem in such cases is that they vastly overproduce Beta amyloid proteins. There's so much that it clumps on its own, even without the presence of microbes!

Then why would some be more vulnerable than others?
Well, it has something to do with brain's ability to clear out the balls of B-amyloid after they have killed the microbes.
For example, people with a gene called ApoE2 have brains that are very good at sweeping out plaque, and have a low risk of AD in old age.
But those with a different version, ApoE2 are inefficient in removing plaque and have a high risk of AD!!

Any new treatment strategy for AD?
Yes! The Cure Alzheimer's Fund is initiating a large collaboration project that will use Gene sequencing technology to carefully look for microbes in plaques found in brains of people who had Alzheimers and those who did not.
Once found, we can aim at stopping them!
Also, scientists have been working on new and reliable blood tests to diagnose the disease at earlier stage so that it can be treated in a better way. :D

That's all!!

-Jaskunwar Singh

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