Lewy bodies: the story so far
In this blog we look back at some of the discoveries that have helped us to understand the clumps of proteins, or Lewy bodies, that form in Parkinson’s.
Lewy bodies are abnormal clumps of proteins that form in the brain cells of people with Parkinson’s. Despite knowing about them since 1912, we still don’t understand exactly what role Lewy bodies play, with some evidence suggesting they may protect cells somehow. Over the years, a number of studies have increased our understanding of Lewy bodies, and we think they could be an exciting potential target for new treatments.
Here we look at some of the significant studies that have shaped our understanding today, and how we’re addressing the unanswered questions.
1912 — Fredrich Lewy first identifies these protein clumps
Dr Friedrich Heinrich Lewy, a German-born neurologist, discovered ‘spherical neuronal inclusions’ in brain regions outside of the substantia nigra, in a post-mortem study of a person with Parkinson’s.
1919 — Konstantin Nikolaevich Tretiakoff found similar clumps in the substantia nigra
He named these clumps ‘Lewy bodies’ after Friedrich.
1965 — Lewy bodies shown to consist of abnormal filaments
Improvements in microscope technology increased our understanding of the structure of Lewy bodies. The first high magnification study revealed that Lewy bodies are circular formations with filaments radiating around the centre. This initial description of Lewy bodies has since been confirmed.
1976 — Dementia with Lewy bodies first described
As well as Parkinson’s, Lewy bodies are a feature of Dementia with Lewy bodies (DLB), a type of dementia that shares symptoms with both Parkinson’s and Alzheimer’s.
In 1976, Kenji Kosaka, a Japanese psychiatrist, first identified Lewy bodies in the outer layers of the brain, the cortex. When Lewy bodies form here, they are associated with dementia with Lewy bodies, which accounts for 10–15% of all cases of dementia.
1997 — Key alpha-synuclein discoveries
In 1997, two important discoveries were made that had a big impact on our understanding of Lewy bodies.
A gene change that causes some cases of Parkinson’s was identified for the first time. Scientists looked at a large Italian family, where many members had been diagnosed with Parkinson’s. They found a change in the SNCA gene, which contains instructions for a protein called alpha-synuclein.
They also found that Lewy bodies from DLB also contain alpha-synuclein, suggesting Lewy bodies from both conditions have similar compositions.
Although alpha-synuclein seems to be particularly important, 90 different molecules have been found in Lewy bodies so far. Others include Parkin, Synphilin-1, Tau and LRRK2 proteins.
1997 — Cells without Lewy bodies undergo more apoptosis
A study in 1997 complicated our understanding of Lewy bodies, by suggesting that the presence of Lewy bodies does not predispose a nerve cell to a type of cell death.
The researchers used a stain that allowed them to identify cells in the initial stages of apoptosis — which is a type of programmed cell death thought to be involved in cell loss in Parkinson’s.
Researchers found that the total number of neurons displaying signs of apoptosis was greater in the cells without Lewy bodies.
This study sheds doubt on the role of Lewy bodies — and raises the question of what effect they have on cells.
2008 — Spread of alpha-synuclein between cells
In the 1980s, some people with Parkinson’s had embryonic dopamine neurons injected into their brains, to replace the ones that had been lost. Fourteen years later, their brains were examined post-mortem. Some of the neurons that had been transplanted contained Lewy bodies, suggesting that alpha-synuclein can move between cells, which we now think is how Parkinson’s spreads through the brain.
2012 — Evidence that Lewy bodies are not the first sign of problems
In 2012, another study raised questions about the role of Lewy bodies.
Researchers examined post-mortem sections of brains from people with Parkinson’s, and found that many cells that did not contain Lewy bodies were dysfunctional or dying. These results suggest that cell death may happen before Lewy bodies form in the neurons.
2018 — Answering the remaining questions about Lewy bodies
Professor Peter Magill has been working in the area of Parkinson’s research for over 20 years. He is just about to start a Parkinson’s UK funded study at the University of Oxford, which aims to answer some questions we still have about Lewy bodies.
Over the three year study, the team will look at mouse models that accurately mimic the activity of Lewy bodies in brain cells. They will use specialist equipment to look at how Lewy bodies affect the way brain cells send electrical signals, release dopamine and control movement — comparing the activity of cells that have Lewy-body like clumps with those that don’t have any clumps. They will also carefully watch how this changes over time.
At the end of the study, the team hope to have clear evidence of why Lewy bodies are important in Parkinson’s, what they do to cells, how they affect the function of cells and when would be the best time to target them.
“We need to focus in on the answers. That’s what I’m addressing with my research. I’m looking to answer the fundamental questions that remain about Lewy bodies, so we can focus in on a clear target for new treatments.”
— Professor Peter Magill
Parkinson’s is a progressive neurological condition that affects about 145,000 people in the UK and an estimated 7–14 million people worldwide. There is currently no cure, and we desperately need better treatments.
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