Neutrophil-to-lymphocyte ratio and lymphocyte count reflect alterations in central neurodegeneration-associated proteins and clinical severity in Parkinson Disease patients.

INTRODUCTION: Peripheral inflammation has been recently associated to Parkinson disease (PD). However, how the peripheral inflammatory immune response could affect the clinical-pathological features of the disease is not fully understood. In this study, we assessed the peripheral immune profile of a well-characterized PD cohort, examining several correlations with CSF biomarkers of neurodegeneration and the main clinical parameters, aimed at better elucidating the complex dynamics of the brain-periphery interactions in PD. METHODS: The leukocyte populations counts (neutrophils, lymphocytes, monocytes, eosinophils, and basophils) and the neutrophil-to-lymphocyte ratio (NLR) were collected and compared in 61 PD patients and 60 sex/age matched controls (CTRLs). Immune parameters were correlated with CSF levels of total α-synuclein, amyloid-ß-42, total and phosphorylated-tau and main motor and non-motor scores. RESULTS: PD patients had lower lymphocyte and higher NLR counts compared to CTRLs. In PD patients, the lymphocyte count directly correlated with CSF α-synuclein levels, whereas NLR displayed an inverse correlation with the CSF amyloid-ß42 levels. The lymphocyte count also negatively correlated with HY stage, while NLR positively with the disease duration. CONCLUSIONS: This study provided in vivo evidence that, in PD, changes in leukocytes in the periphery, assessed as relative lymphopenia and NLR increase, reflect in central neurodegeneration-associated proteins modifications, especially in α-synuclein and amyloid-ß pathways, and greater clinical burden.

Sex hormones differentially contribute to Parkinson disease in males: A multimodal biomarker study.

BACKGROUND AND PURPOSE: Parkinson disease (PD) presents relevant sex-related differences in epidemiology, pathophysiology, and clinical features, with males being more vulnerable to the disease. Sex hormones might have a role, as the experimental models suggest; however, human-based evidence is scarce. Here, we integrated multimodal biomarkers to investigate the relationships between circulating sex hormones and clinical-pathological features in male PD patients. METHODS: A cohort of 63 male PD patients underwent comprehensive clinical evaluation of motor and nonmotor disturbances; measurement of estradiol, testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) blood levels; and cerebrospinal fluid (CSF) assay of total α-synuclein, amyloid-ß-42, amyloid-ß-40, total tau, and phosphorylated-181 tau levels. A subgroup of 47 PD patients underwent brain volumetry by 3-T magnetic resonance imaging for further correlations. A control group of 56 age-matched individuals was enrolled for comparative analyses. RESULTS: Male PD patients had higher estradiol and testosterone levels than controls. Estradiol had independent inverse associations with Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part 3 score and disease duration; it was also lower in nonfluctuating patients. Testosterone had inverse independent correlations with CSF α-synuclein and right globus pallidus volume. FSH and LH had age-dependent correlations with cognitive impairment and CSF amyloid-ß-42/amyloid-ß-40 ratio. CONCLUSIONS: The study suggested that sex hormones could differentially contribute to clinical-pathological features of PD in male patients. Whereas estradiol might have a protective role in motor impairment, testosterone might be involved in male vulnerability to PD neuropathology. Gonadotropins instead might mediate age-dependent phenomena of amyloidopathy and cognitive decline.

Organic geochemistry and mineralogy suggest anthropogenic impact in speleothem chemistry from volcanic show caves of the Galapagos.

The network of lava tubes is one of the most unexploited natural wonders of the Galapagos Islands. Here, we provide the first morphological, mineralogical, and biogeochemical assessment of speleothems from volcanic caves of the Galapagos to understand their structure, composition, and origin, as well as to identify organic molecules preserved in speleothems. Mineralogical analyses revealed that moonmilk and coralloid speleothems from Bellavista and Royal Palm Caves were composed of calcite, opal-A, and minor amounts of clay minerals. Extracellular polymeric substances, fossilized bacteria, silica microspheres, and cell imprints on siliceous minerals evidenced microbe-mineral interactions and biologically-mediated silica precipitation. Alternating depositional layers between siliceous and carbonate minerals and the detection of biomarkers of surface vegetation and anthropogenic stressors indicated environmental and anthropogenic changes (agriculture, human waste, and cave visits) on these unique underground resources. Stable isotope analysis and Py-GC/MS were key to robustly identify biomarkers, allowing for implementation of future protection policies.