What exactly happens in the brain when Alzheimer’s disease strikes?

PUBLISHED BY SBS SCIENCE IN Sept 2016

 
Neurons send messages along their axons, pictured here in green, to neighbouring cells in the brain and on to the rest of the body [Image courtesy of  Rachelle Balez , PhD candidate, University of Wollongong]

Neurons send messages along their axons, pictured here in green, to neighbouring cells in the brain and on to the rest of the body [Image courtesy of Rachelle Balez, PhD candidate, University of Wollongong]

 
 

Here's how you can understand what happens in the brain when it strikes.

Since Alois Alzheimer’s first description in 1906, amyloid-beta has been linked to Alzheimer’s disease.

Alzheimer, conducting a post-mortem study of a woman who had died with dementia, noted abnormal “plaques” and “tangles” in her brain tissue. The woman had shown symptoms of disorientation, memory loss and unpredictable behaviour.

What is amyloid-beta?

The 37 trillion cells in our bodies usually function as a well-oiled machine. Proteins are produced by our cells for different purposes - some as structural pillars, some as transporters and others as reactive species for our immune system. If proteins perform the job poorly, they are swiftly cleared and destroyed.

However, with age this system can falter. That’s the main risk factor for Alzheimer’s: beyond 85 years, almost one in three people will develop the disease.

Amyloid-beta is small protein, cut from a larger precursor, known to gradually form abnormal clumps, or plaques, in brain tissue as Alzheimer’s disease develops. These amyloid plaques become toxic and are one hallmark of Alzheimer’s; the other is tangled bundles of tau, another misbehaving protein.

Protein aggregates are also found in other neurodegenerative diseases, like Parkinson’s and Motor Neuron Disease, but the chief protein differs in each case.

How does amyloid-beta form plaques?

The formation of amyloid plaques occurs in the early stages of Alzheimer’s, silently, before symptoms have appeared. This is why targeting amyloid-beta is an attractive strategy in the search for preventative medicines.

Single amyloid-beta units can spontaneously clump together, or assemble layer upon layer, folding in pleated sheets. One becomes two, three becomes four – a chain reaction that results in sticky bundles building up in the space between cells in the brain. 

Why do scientists think this causes Alzheimer’s?

Clumps of amyloid-beta are very disruptive to neuronal cells in the brain, which usually fire rapid electrical signals amongst themselves. To send messages to their neighbours (and on to the rest of the body), neurons use chemical transmitters that cross the gaps between cells. Here, amyloid plaques are like a traffic jam, blocking cell signalling. Connections between cells are lost - first in the hippocampus, the region in the brain for memory and learning. Neurons die and the affected brain tissue shrinks.

Amyloid plaques can also trigger an inflammatory response, since to cells the protein plaques seem foreign and are unwanted. The body’s normal immune system responds rightly and attacks amyloid plaques, trying to clear them, but damages useful cells in the process.

There is no diagnostic screening test for Alzheimer’s. Doctors rely on cognitive tests and a collaborative history from family members; a definitive diagnosis can be made only after death with an examination of brain tissue in an autopsy. With advances in brain imaging techniques and new methods of modelling the disease, scientists are building a more dynamic picture of how amyloid plaques form, and how we might be able to recognise and prevent the onset of this disease. 

What are the most promising treatment options right now?

Scientists are taking different approaches to diagnosing and treating Alzheimer’s disease at an early stage. Promising strategies for early detection include tagging amyloid plaques with imaging agents so that they can be visualised on a brain scan years before symptoms arise.

Several new treatments designed to clear amyloid plaques are in trial. Most efforts are immunotherapies, which enhance the precision of the immune system against amyloid-beta by administering an anti-amyloid vaccine or supplying ready-made antibodies.

Researchers are also looking at lifestyle changes that could have therapeutic benefits. Linked to circadian rhythms, amyloid-beta production falls as we sleep and rises during waking hours to the point where patients’ symptoms can be exacerbated late in the day. Minimising sleep disturbances could limit amyloid aggregation and reduce the risk of developing the disease.

With these advancements for Alzheimer’s disease, there is hope on the horizon.