Can neuroinflammation be used as a biomarker for Parkinson’s disease?

2012  -  Toronto, ON, CA


Toronto Western Hospital, Centre for Additction and Mental Health

Project Description

Microglia, a type of cell in the brain, continuously perform repair tasks in response to neurological micro-insults. Activated microglia thus represent an important marker of neuroinflammation. To date, most of the imaging studies with Positron Emission Tomography (PET) in Parkinson’s disease (PD) have focused on investigating dopaminergic neural changes. Our project intends to shift the focus from neuronal targets to microglial activation in different areas of the brain to investigate the role of neuroinflammation as a possible contributing factor and/or response to neurodegeneration. We will use a novel PET radioligand, [18F]FEPPA, which may provide reliable evidence in vivo of increased microglial activation in the brain of patients with PD.

Relevance to the acceleration of therapeutics for neurodegenerative diseases of aging

This study may provide the first reliable evidence of neuroinflammation in vivo in the brain of patients with PD. The possibility of detecting microglial changes may have very important implications at several levels. In fact, we could envision the use of this new tracer as a biomarker for the detection of PD in the pre-symptomatic or very early stage, as an indicator of disease severity, an assessment tool for neuro-protection studies or a novel biomarker for different outcome-measures for treatment strategies. More importantly, the validation of this new PET radiotracer may allow a broader application to test neuroinflammation in other neurological diseases such as Alzheimer’s disease, multiple sclerosis and stroke.

Anticipated Outcome

Post-mortem studies have shown evidence of a widespread increase of microglial activation in PD, not only in the substantia nigra and putamen structures of the brain but also in the hippocampus, cingulate and temporal cortex. Interestingly, animal models also seem to suggest that microglial activation may precede neuronal degeneration. Thus, we predict that 1) [18F]FEPPA binding may be significantly increased in the striatum of PD patients compared to age-matched controls; 2) we will also consider the possibility of detecting significant increases in binding in several brain areas that may precede the clinical expression of non-motor symptoms (i.e., cognitive complications) in PD; 3) we hypothesize that those PD patients with a widespread increase of microglial activation in cortical regions of the brain will express more cognitive deterioration.

Final Abstract

Positron Emission Tomography (PET) targeting for translocator protein (TSPO) allows for the quantification of neuroinflammation in vivo. This study investigated whether TSPO imaging using the [18F]-FEPPA tracer could be used in parkinsonian disorders as a biomarker for detecting neuroinflammation. Neuroinflammation has been implicated as a potential mechanism for the disease progression in Parkinson’s disease (PD). Based on genotype of the rs6791 polymorphism, high-affinity binders (HABs) were identified for this study. Participants received as well a PET scan with [11C] PIB tracer to rule out amyloid deposition which may also play a certain role in neuroinflammation. The analysis of the 2 different tracers did not show any difference in cerebral uptake and distribution between PD and HC in cortical and subcortical regions for both [18F]-FEPPA and [11C] PIB. Similarly, there was no correlation between clinical measures and tracer bindings, implying that disease severity is not associated with TSPO expression and amyloid deposition in PD patients.