RESUMEN
Background: Parkinson's disease (PD) is characterized by proteinopathies and these proteinopathies seem to interact synergistically and lead to protein aggregations and changes in protein cerebrospinal fluid (CSF) levels. In this study, we aimed to explore the longitudinal changes of CSF a lpha-synuclein (α-syn), total tau (t-tau), phosphorylated tau (p-tau), and beta-amyloid (Aß1-42) and their relationships with each other and with baseline clinical entities like REM sleep behavior disorder (RBD), cognitive impairment, motor symptoms, and olfaction dysfunction. Method: One hundred and twelve non-demented PD patients and 110 controls were recruited from Parkinson's Progression Markers Initiative (PPMI).We used a linear mixed model within groups to assess longitudinal protein changes over 6 and 12 months and a random regression coefficient within the linear mixed model to investigate the correlation between proteins and their baseline clinical characteristics. Results: P-tau was lower in PDs only at baseline, but during a year, p-tau increased more rapidly in PDs than controls. Aß1-42 was not significantly different between groups at any separate timepoint; however, when assessed longitudinally, Aß1-42 showed significant changes in both groups. Conversely, t-tau and α-syn differed significantly between groups, but their longitudinal changes were not significant in either of the groups. Moreover, all proteins' baseline levels, except p-tau, could determine estimated longitudinal tau changes. Baseline RBDSQ scores but not UPDRS III, MoCA, or UPSIT scores were predictive of longitudinal increase in α-syn levels. Conclusion: Longitudinal changes in levels of CSF proteins are related to each other and could help researchers further understand PD pathology. In addition, RBD seems to be a potential prognostic factor for PD progression. However, in order to reach a consensus, longer follow-up times are required.
RESUMEN
In the context of growing evidence supporting disturbed neural connectivity in the pathogenesis of depressive symptoms, we used the diffusion tensor imaging technique to investigate white matter disruptions in previously undiagnosed and hence treatment-naive young adults with mild and moderate depressive symptoms screened by Beck's Depression Inventory test compared with age-matched and sex-matched healthy controls. This is the first diffusion tensor imaging study to assess minor forms of depression. We hypothesized that subthreshold depressive symptoms share the same neural disruptions as major depressive disorder (MDD). Each group included 47 participants with a mean age of 20.1±1.1 years. The exploratory region of interest method was used to assess integrity (fractional anisotropy and mean diffusivity) in 48 regions of the brain based on Mori atlas. Data were recruited from the Southwest University Longitudinal Imaging Multimodal Brain Data Repository. The following pathways showed significant microstructural changes by means of reduced fractional anisotropy in the group with depressive symptoms compared with normal participants: pontine crossing tract; genu of the corpus callosum; posterior limb of the internal capsule (bilaterally); and anterior, posterior, and superior corona radiata (bilaterally). None of the above regions, but the middle cerebellar peduncle and the right superior fronto-occipital fasciculus were shown to differ significantly in the mean diffusivity values between the two groups. On the basis of the current results, our findings provide evidence that the white matter impairments in the interhemispheric connections and frontal-subcortical neural circuits may play a key role in the pathogenesis of depression in young adults. The similarity of neural underpinnings in MDD and minor depressive disorder in this study further proves that these two mood disorders exist in a continuum, and milder depressive symptoms can herald a major episode. Besides the high prevalence and great burden of subthreshold forms of depression on personal and social aspects of life, there is lack of knowledge of them and most studies have mainly focused on MDD. This study provides a new avenue in addressing neuropathology of depression, mainly in subtle forms that are almost always overlooked.