An autoimmune reaction in mice to a protein associated with Parkinson's disease damaged neurons in the GI tract, adding to evidence that the disease may get its start in the gut. Credit: David Sulzer
Two new studies are shedding more light on Parkinson’s disease, both focusing on how to identify and diagnose the neurodegenerative disease earlier in the hopes of better treatment or even prevention.
A research team at Columbia University has added evidence to the hypothesis that Parkinson’s actually starts in the gut years before any brain changes can be observed. Meanwhile, scientists at University College London used eye scans to identify markers that indicate the presence of Parkinson’s disease in patients on average seven years before clinical presentation.
Autoimmunity and the gut
Previous research by neurobiology professor David Sulzer pointed toward the role of an autoimmune response in Parkinson’s disease, so his team dug deeper.
In Parkinson’s, a protein called alpha-synuclein becomes misfolded, accumulates inside neurons and slowly poisons the cells. Sulzer’s lab noticed that small portions of the misfolded alpha-synuclein can also appear on the outside of neurons, which makes the neurons vulnerable to attack from the immune system.
“The blood of Parkinson’s patients often contains immune cells that are primed to attack the neurons, but it’s not clear where or when they are primed,” said Sulzer.
Still, he and his team were immediately suspicious of gut.
To test their theory, the researchers created a mouse capable of displaying pieces of misfolded alpha-synuclein on cell surfaces (since natural mice do not have this ability). Then, they injected the mice with alpha-synuclein and monitored what happened in the brain and the gut.
According to the study results, published in Neuron, the researchers did not see any signs resembling Parkinson’s disease in the brain, but they did see that an immune attack on neurons in the gut produced constipation and other gastrointestinal effects resembling those seen in most Parkinson’s patients years before they are clinically diagnosed with the disease.
“This shows that an autoimmune reaction can lead to what appears to be the early stages of Parkinson’s, and is strong support that Parkinson’s is in part an autoimmune disease,” said Sulzer.
That means that the early detection and intervention of an immune response in the gut could prevent a later attack on the brain’s neurons—stopping Parkinson’s in its tracks.
Retinal imaging
In the largest study to date on retinal imaging in Parkinson’s disease, researchers at University London College identified markers that indicate the presence of the neurogenerative disease in patients nearly 7 years before clinical presentation.
The team used the AlzEye database, as well as the UK Biobank as healthy controls to detect the subtle markers.
Post-mortem examination of patients with Parkinson’s disease has found differences in the inner nuclear layer (INL) of the retina. Previous studies using a type of 3D scan known as optical coherence tomography (OCT) scans have also found potential morphological abnormalities associated with the disease—but with inconsistencies.
According to the new study, published in The Lancet Digital Health, results confirmed previous reports of a significantly thinner ganglion cell–inner plexiform layer (GCIPL), while for the first time finding a thinner INL. It further found that a reduced thickness of these layers was associated with increased risk of developing Parkinson’s disease, beyond that conferred by other factors or comorbidities.
Future studies are needed to determine whether progression of GCIPL atrophy is driven by brain changes in Parkinson’s disease, or if INL thinning precedes GCIPL atrophy. Exploring this could help explain the mechanism and determine whether retinal imaging could support the diagnosis, prognosis and management of patients affected by Parkinson’s disease.