Type-2-diabetes (T2D) has surfaced as a potential risk factor for Parkinson's disease (PD) in some epidemiological studies. Evidence of glucose metabolism alterations in PD from molecular studies ...remains conflicting. Amylin, the T2D amyloid protein, has been implicated in PD in pathological studies. We aimed to assess peripheral levels of amylin and insulin in PD patients and control subjects (Cs).
We conducted an observational cross-sectional study of 111 participants: 73 PD and 38 Cs, similar in age, sex and body mass index. All underwent motor (UPDRS-MDS-III), non-motor (NMSS) and cognitive (MDRS) scales as well as determination of four parameters: fasting glycaemia, glycated haemoglobin, fasting plasma insulin (FPI) and fasting plasma amylin (FPA).
FPI was significantly lower in PD than Cs (p = 0.034). In participants with age above cohort-median-age, FPA was higher in PD than Cs (p = 0.046). The FPA/FPI ratio (FPAIR) was significantly higher in PD than Cs (p = 0.024). In PD, modest correlation was found between higher insulin-resistance and NMSS scores.
PD patients had lower FPI and increased FPAIR. In older PD subgroup, FPA was increased. The more the insulin resistance, the higher the non-motor scores. These findings provide an additional link between pathophysiology of diabetes and PD. This might be related to a dissociated insulin and amylin secretion in PD, in line with recent evidence of endocrine pancreas role in PD pathogeny.
•Parkinson's disease (PD) patients had lower insulin levels than healthy controls.•Plasma amylin was higher in older PD patients and plasma amylin/insulin ratio was higher too in PD.•Higher values of HOMA-IR (insulin resistance) were related to increased non-motor symptoms scores (NMSS).
Over the last two decades there have been meaningful developments on biomarkers of neurodegenerative diseases, extensively (but not solely) focusing on their proteinopathic nature. Accordingly, in ...Alzheimer's disease determination of levels of total and phosphorylated tau (τ and p-τ, usually p-τ181) along with amyloid-beta1-42 (Aβ1-42) by immunodetection in cerebrospinal fluid (CSF) and currently even in peripheral blood, have been widely accepted and introduced to routine diagnosis. In the case of Parkinson's disease, α-synuclein as a potential biomarker (both for diagnosis and progression tracking) has proved more elusive under the immunodetection approach. In recent years, the emergence of the so-called seed amplification assays is proving to be a game-changer, with mounting evidence under different technical approaches and using a variety of biofluids or tissues, yielding promising diagnostic accuracies. Currently the least invasive but at once more reliable source of biosamples and techniques are being sought. Here we overview these advances.
•Highly reliable and accurate biomarkers are an unmet need in Parkinson's disease.•Besides imaging, extensive work has been done on fluid and tissue biomarkers.•The most studied and obvious candidate has been α-synuclein in cerebrospinal fluid.•Immunodetection has been inconsistent with seed amplification assays having emerged lately.•Evidence is increasing for all these biomarkers in other fluids (blood) and tissues (skin).
The Tibetan Plateau is the product of crustal thickening caused by collision between India and Asia. Plate tectonic reconstructions suggest continuous northward movement of the Indian plate relative ...to stable Eurasia at nearly 50 mm/yr for the last 50 My. The plateau is now at ~5 km elevation with steep topographic gradients across the southern and northern margins. These steep topographic gradients are also related to large lateral variations in the geoid and gravity anomalies. In a SSW to NNE cross section, the Bouguer gravity anomaly decreases over a distance of 500 km from about 0 mGal in the India plate to ~−500 mGal on the Tibetan Plateau. The geoid anomaly also presents steep gradients on both the Himalayan front and the northern margin, reaching values between 20–30 m on the plateau, suggesting a pronounced thinning of the lithospheric mantle. Uplift late in the tectonic evolution of the plateau, the widespread extension, and the associated magmatism have been attributed to convective removal of the lower part of lithospheric mantle and its replacement by hotter and lighter asthenosphere. Here we present a two-dimensional lithospheric thermal and density model along a transect from the Indian plate to Asia, crossing the Himalaya front and the Tibetan Plateau. The model is based on the assumption of local isostatic equilibrium, and is constrained by the topography, gravity and geoid anomalies and by thermal data within the crust. Our results suggest that the height of the Tibetan Plateau is compensated by thick crust in the south and by hot upper mantle to the north. The Tibetan Plateau as a whole cannot be supported isostatically only by thickened crust; a thin and hot lithosphere beneath the northern plateau is required to explain the high topography, gravity, geoid and crustal temperatures. The lithosphere reaches a maximum depth of ~260 km beneath the southern Plateau, and thins abruptly northward to ~100 km under the central and northern Plateau. The lithosphere depth increases again beneath the Qaidam basin and the Qilian Shan to ~160 km.
The geodynamic evolution of the Western Mediterranean related to the closure of the Ligurian-Tethys ocean is not yet fully resolved. We present a new 3D numerical model of double subduction with ...opposite polarities fostered by the inherited segmentation of the Ligurian-Tethys margins and rifting system between Iberia and NW Africa. The model is constrained by plate kinematic reconstructions and assumes that both Alboran-Tethys and Algerian-Tethys plate segments are separated by a NW-SE transform zone enabling that subduction polarity changes from SE-dipping in the Alboran-Tethys segment to NW-dipping in the Algerian-Tethys segment. The model starts about late Eocene times at 36.5 Ma and the temporal evolution of the simulation is tied to the geological evolution by comparing the rates of convergence and trench retreat, and the onset and end of opening in the Alboran Basin. Curvature of the Alboran-Tethys slab is imposed by the pinning of its western edge when reaching the end of the transform zone in the adjacent west-Africa continental block. The progressive curvature of the trench explains the observed regional stress reorientation changing from N-S to NW-SE and to E-W in the central and western regions of the Alboran Basin. The increase of the retreat rates from the Alboran-Tethys to the Algerian-Tethys slabs is compatible with the west-to-east transition from continental-to-magmatic-to-oceanic crustal nature and with the massive and partially synchronous calc-alkaline and alkaline magmatism.
•We propose a 3D numerical model of opposing subduction simulating the tectonic setting of the Western Mediterranean.•The retreat rates of the slabs are consistent with the duration of opening of the Alboran and Algerian basins.•The progressive curvature of the Alboran-Tethys slab is consistent with the regional stress evolution of the Alboran Basin.
MicroRNA (miRNA) misregulation in peripheral blood has been linked to Parkinson disease (PD) but its role in the disease progression remains elusive. We performed an explorative genome-wide study of ...miRNA expression levels in dopaminergic neurons (DAn) from PD patients generated by somatic cell reprogramming and induced pluripotent stem cells differentiation. We quantified expression levels of 377 miRNAs in DAn from 3 sporadic PD patients (sPD), 3 leucine-rich repeat kinase 2–associated PD patients (L2PD) (total 6 PD), and 4 healthy controls. We identified differential expression of 10 miRNA of which 5 were upregulated in PD (miR-9-5p, miR-135a-5p, miR-135b-5p, miR-449a, and miR-449b-5p) and 5 downregulated (miR-141–3p, miR-199a-5p, miR-299–5p, miR-518e-3p, and miR-519a-3p). Changes were similar in sPD and L2PD. Integrative analysis revealed significant correlations between miRNA/mRNA expression. Moreover, upregulation of miR-9-5p and miR-135b-5p was associated with downregulation of transcription factors related to the DNA hypermethylation of enhancer elements in PD DAn (FOXA1 and NR3C1). In summary, miRNA changes are associated with monogenic L2PD and sPD and co-occur with epigenetic changes in DAn from PD patients.
LitMod2D integrates geophysical and petrological data sets to produce the thermal, density, and seismic velocity structure of the lithosphere and upper mantle. We present a new LitMod2D_2.0 package ...with improvements focused on (i) updated anelastic attenuation correction for anharmonic seismic velocities, (ii) chemical composition in the sublithospheric mantle, and (iii) incorporation of sublithospheric mantle anomalies. Sublithospheric mantle anomalies can be defined with different chemical composition, temperature, seismic velocities, and a combination of them, allowing the application of LitMod2D_2.0 to regions affected by mantle upwelling, subduction, delamination, and metasomatism. We demonstrate the potential application of LitMod2D_2.0 to such regions and the sensitivity of thermal and compositional anomalies on density and seismic velocities through synthetic models. Results show nonlinearity between the sign of thermal and seismic velocity anomalies, and that S wave velocities are more sensitive to temperature whereas P wave velocities are to composition. In a synthetic example of subduction, we show the sensitivity of sublithospheric mantle anomalies associated with the slab and the corner flow on surface observables (elevation, geoid height, and gravity anomalies). A new open‐source graphic user interface is incorporated in the new package. The output of the code is simplified by writing only the relevant physical parameters (temperature, pressure, material type, density, and seismic velocities) to allow the user using predefined post‐processing codes from a toolbox (flexure, mineral assemblages, synthetic passive seismological data, and tomography) or designing new ones. We demonstrate a post‐processing example calculating synthetic seismic tomography, Rayleigh surface‐wave dispersion curves, and P wave receiver functions from the output file of LitMod2D_2.0.
Key Points
LitMod2D_2.0 allows studying the thermal and chemical nature of upper mantle anomalies
A new open‐source graphic user interface is provided
Post‐processing toolbox for tailored processing of the output is added
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