The Spread of Lewy Bodies

Parkinson's disease and Lewy body disease are caused by abnormal protein known as alpha-synuclein, which clumps into Lewy bodies. The idea that alpha-synuclein might spread from neuron to neuron arose when fetal nerve tissue was transplanted into patients with Parkinson's and then that tissue developed Lewy bodies. This indicated that nearby diseased cells had infected the transplanted tissue. Studies subsequently showed that alpha-synuclein can spread between neighboring cells and cause cell death. (Similarly, an abnormal protein found in Alzheimer's disease can spread from cell to cell, as we noted earlier.) The question remained as to whether the spread of alpha-synuclein could account for the damage typical of Parkinson's disease.

In a study published in November 2012, a team from the University of Pennsylvania in Philadelphia injected alpha-synuclein into the brains of normal mice and saw the key characteristics of Parkinson's disease develop and progressively worsen. The injected sites developed Lewy bodies and nerve cells nearby did as well, suggesting that the abnormal protein had spread from cell to cell. Within six months of the injection, coordination of movement, grip strength, and balance had deteriorated in the mice, as it does in people with Parkinson's disease.

Researchers are now interested in the possibility that an antibody that binds alpha-synuclein could intercept the protein as it passes between nerve cells. That would limit the spread of the abnormal protein.

This study sheds light on how Lewy bodies spread. An unresolved issue is why Lewy bodies appear in the first place. Those with Parkinson's disease have Lewy bodies in the mid-brain; those with Lewy body disease have Lewy bodies in the mid-brain and in the brain's cortex (the outer layer of gray matter).

A press release about the study is available. The scientific paper was published in Science.