RESUMO
Neuroinflammation through enhanced innate immunity is thought play a role in the pathogenesis of Parkinson's disease (PD). Methods for monitoring neuroinflammation in living patients with PD are currently limited to positron emission tomography (PET) ligands that lack specificity in labeling immune cells in the nervous system. The colony stimulating factor 1 receptor (CSF1R) plays a crucial role in microglial function, an important cellular contributor to the nervous system's innate immune response. Using immunologic methods, we show that CSF1R in human brain is colocalized with the microglial marker, ionized calcium binding adaptor molecule 1 (Iba1). In PD, CSF1R immunoreactivity is significantly increased in PD across multiple brain regions, with the largest differences in the midbrain versus controls. Autoradiography revealed significantly increased [3H]JHU11761 binding in the inferior parietal cortex of PD patients. PET imaging demonstrated that higher [11C]CPPC binding in the striatum was associated with greater motor disability in PD. Furthermore, increased [11C]CPPC binding in various regions correlated with more severe motor disability and poorer verbal fluency. This study finds that CSF1R expression is elevated in PD and that [11C]CPPC-PET imaging of CSF1R is indicative of motor and cognitive impairments in the early stages of the disease. Moreover, the study underscores the significance of CSF1R as a promising biomarker for neuroinflammation in Parkinson's disease, suggesting its potential use for non-invasive assessment of disease progression and severity, leading to earlier diagnosis and targeted interventions.
RESUMO
Motor impairments are only one aspect of Parkinson's disease (PD), which also include cognitive and linguistic impairments. Speech-derived interpretable biomarkers may help clinicians diagnose PD at earlier stages and monitor the disorder's evolution over time. This study focuses on the multilingual evaluation of a composite array of biomarkers that facilitate PD evaluation from speech. Hypokinetic dysarthria, a motor speech disorder associated with PD, has been extensively analyzed in previously published studies on automatic PD evaluation, with a relative lack of inquiry into language and task variability. In this study, we explore certain acoustic, linguistic, and cognitive information encoded within the speech of several cohorts with PD. A total of 24 biomarkers were analyzed from American English, Italian, Castilian Spanish, Colombian Spanish, German, and Czech by conducting a statistical analysis to evaluate which biomarkers best differentiate people with PD from healthy participants. The study leverages conceptual robustness as a criterion in which a biomarker behaves the same, independent of the language. Hence, we propose a set of speech-based biomarkers that can effectively help evaluate PD while being language-independent. In short, the best acoustic and cognitive biomarkers permitting discrimination between experimental groups across languages were fundamental frequency standard deviation, pause time, pause percentage, silence duration, and speech rhythm standard deviation. Linguistic biomarkers representing the length of the narratives and the number of nouns and auxiliaries also provided discrimination between groups. Altogether, in addition to being significant, these biomarkers satisfied the robustness requirements.
