The development of biomarkers to predict the progression of Parkinson’s disease (PD) from its earliest stage through its heterogeneous course is critical for research and therapeutic development. The Parkinson’s Progression Markers Initiative (PPMI) study is an ongoing international multicenter, prospective study to validate biomarkers in drug-naïve PD patients and matched healthy controls (HC). We quantified cerebrospinal fluid (CSF) alpha-synuclein (α-syn), amyloid-beta1–42 (Aβ1–42), total tau (t-tau), and tau phosphorylated at Thr181 (p-tau) in 660 PPMI subjects at baseline, and correlated these data with measures of the clinical features of these subjects. We found that CSF α-syn, t-tau and p-tau levels, but not Aβ1–42, were significantly lower in PD compared with HC, while the diagnostic value of the individual CSF biomarkers for PD diagnosis was limited due to large overlap. The level of α-syn, but not other biomarkers, was significantly lower in PD patients with non-tremor-dominant phenotype compared with tremor-dominant phenotype. In addition, in PD patients the lowest Aβ1–42, or highest t-tau/Aβ1–42 and t-tau/α-syn quintile in PD patients were associated with more severe non-motor dysfunction compared with the highest or lowest quintiles, respectively. In a multivariate regression model, lower α-syn was significantly associated with worse cognitive test performance. APOE ε4 genotype was associated with lower levels of Aβ1–42, but neither with PD diagnosis nor cognition. Our data suggest that the measurement of CSF biomarkers in early-stage PD patients may relate to disease heterogeneity seen in PD. Longitudinal observations in PPMI subjects are needed to define their prognostic performance.

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Underserved minorities are vulnerable to diagnostic delays and under-treatment of Parkinson’s disease (PD). The purpose of this mixed-methods study was to understand knowledge and attitudes about PD among a racially/ethnically diverse group of community members. In the qualitative arm, 10 homogeneous focus groups of 6 to 8 White, African-American and Chinese-Americans older adults at senior centers in Philadelphia were conducted. Next, for the quantitative piece, a questionnaire of knowledge and attitudes about PD was administered among a larger group of senior center members. Themes were identified from the focus group discussions. ANOVA and chi-square tests were used to assess differences in PD knowledge and attitudes among the different racial/ethnic groups. Logistic regression analyzed for independent factors associated with barriers to treatment. Seventy-five adults participated in the focus groups (23 Whites, 36 African-Americans and 16 Chinese-Americans) and 154 completed the questionnaire (62 Whites, 47 African-Americans and 45 Chinese-Americans). One common theme about developing PD was fear of losing independence. Racial/ethnic groups identified unique barriers to care: mistrust in the healthcare system by African-Americans and language difficulties by Chinese-Americans. 80% of all participants had no to some knowledge of PD. African-Americans and Chinese-Americans were more likely to perceive PD as a part of normal aging than whites. Chinese-Americans were more likely to perceive barriers to treatment than whites. A diverse sample of older adults demonstrated low levels of PD knowledge through both qualitative and quantitative methods. Many barriers to PD care were identified. Targeted community outreach and education efforts should incorporate information about PD and how to receive care.

In mice, retinal vascular and astrocyte networks begin to develop at birth, expanding radially from the optic nerve head (ONH) towards the retinal periphery. The retinal vasculature grows towards the periphery ahead of differentiated astrocytes, but behind astrocytic progenitor cells (APCs) and immature astrocytes. Endothelial cell specific Vegfr-2 disruption in newborn mice not only blocked retinal vascular development but also suppressed astrocytic differentiation, reducing the abundance of differentiated astrocytes while causing the accumulation of precursors. By contrast, retinal astrocytic differentiation was accelerated by the exposure of wild-type newborn mice to hyperoxia for 24 hours, or by APC specific deficiency in hypoxia inducible factor (HIF)−2α, an oxygen labile transcription factor. These findings reveal a novel function of the retinal vasculature, and imply that in normal neonatal mice, oxygen from the retinal circulation may promote astrocytic differentiation, in part by triggering oxygen dependent HIF-2α degradation in astrocytic precursors.