ELISA Measurement of Specific Non-antigen-bound Antibodies to Ab1-42 Monomer and Soluble Oligomers in Sera from Alzheimer\u27s Disease, Mild Cognitively Impaired, and Noncognitively Impaired Subjects

The article presents a study for enzyme-linked immunosorbent assay (ELISA) measurement of specific non-antigen-bound antibodies to Aβ1-42 monomer and soluble oligomers in Alzheimer\u27s disease (AD), mild cognitively impaired (MCI), and noncognitively impaired (NCI) sera. In the study, serum samples were obtained from the Rush Alzheimer\u27s Disease Center, Chicago, Illinois

New Frontiers-class Uranus Orbiter: Exploring the feasibility of achieving multidisciplinary science with a mid-scale mission

n/

Neptune Odyssey: A Flagship Concept for the Exploration of the Neptune–Triton System

The Neptune Odyssey mission concept is a Flagship-class orbiter and atmospheric probe to the Neptune-Triton system. This bold mission of exploration would orbit an ice-giant planet to study the planet, its rings, small satellites, space environment, and the planet-sized moon Triton. Triton is a captured dwarf planet from the Kuiper Belt, twin of Pluto, and likely ocean world. Odyssey addresses Neptune system-level science, with equal priorities placed on Neptune, its rings, moons, space environment, and Triton. Between Uranus and Neptune, the latter is unique in providing simultaneous access to both an ice giant and a Kuiper Belt dwarf planet. The spacecraft - in a class equivalent to the NASA/ESA/ASI Cassini spacecraft - would launch by 2031 on a Space Launch System or equivalent launch vehicle and utilize a Jupiter gravity assist for a 12 yr cruise to Neptune and a 4 yr prime orbital mission; alternatively a launch after 2031 would have a 16 yr direct-to-Neptune cruise phase. Our solution provides annual launch opportunities and allows for an easy upgrade to the shorter (12 yr) cruise. Odyssey would orbit Neptune retrograde (prograde with respect to Triton), using the moon's gravity to shape the orbital tour and allow coverage of Triton, Neptune, and the space environment. The atmospheric entry probe would descend in ~37 minutes to the 10 bar pressure level in Neptune's atmosphere just before Odyssey's orbit-insertion engine burn. Odyssey's mission would end by conducting a Cassini-like "Grand Finale,"passing inside the rings and ultimately taking a final great plunge into Neptune's atmosphere

CSF Nrf2 and HSPA8 in Parkinson\u27s disease patients with and without LRRK2 gene mutations

Leucine-rich repeat kinase 2 (LRRK2) gene mutations are the most common genetic cause of Parkinson\u27s disease (PD). CSF specimens from LRRK2 + PD patients and healthy LRRK2 mutation carriers are, therefore, useful for biomarker studies. This study examined the hypothesis that differences are present between subjects with sporadic PD (sPD), PD carriers of LRRK2 mutations (LRRK2 + PD), healthy control subjects lacking LRRK2 mutations (CTL), and LRRK2 mutation-carrying healthy controls (LRRK2 + CTL) for CSF concentrations of six potential PD biomarkers. Two of these proteins, nuclear factor (erythroid-derived 2)-like 2 ( Nrf2 ) and heat shock 70 kDa protein 8 ( HSPA8 ), were detected in preliminary ELISAs, then measured in a larger cohort (60 sPD, 10 LRRK2 + PD, 23 CTL, 31 LRRK2 + CTL). No statistically significant differences were found between the groups (Nrf2 p = 0.13, HSPA8 p = 0.21). Nrf2 concentrations in LRRK2 + PD subjects were strongly positively associated with Unified Parkinson\u27s Disease Rating Scale (UPDRS) total and motor scores [Spearman rho = 0.77 (p = 0.012) and 0.83 (p = 0.005)] and negatively associated with Montreal Cognitive Assessment (MoCA) scores (rho = -0.57; p = 0.11). Partial correlation coefficient calculations indicated that disease duration contributed to the associations of Nrf2 levels with UPDRS scores and with MoCA scores in this group. While CSF Nrf2 and HSPA8 do not appear to offer diagnostic biomarkers for PD, the associations between Nrf2 levels and UPDRS scores in LRRK2 + PD patients merit further investigation

α-Synuclein and anti-α-synuclein antibodies in Parkinson's disease, atypical Parkinson syndromes, REM sleep behavior disorder, and healthy controls.

α-synuclein is thought to play a key role in Parkinson's disease (PD) because it is the major protein in Lewy bodies, and because its gene mutations, duplication, and triplication are associated with early-onset PD. There are conflicting reports as to whether serum and plasma concentrations of α-synuclein and anti-α-synuclein antibodies differ between PD and control subjects. The objectives of this study were to compare the levels of α-synuclein and its antibodies between individuals with typical PD (n=14), atypical Parkinson syndromes (n=11), idiopathic rapid eye movement sleep behavior disorder (n=10), and healthy controls (n=9), to assess the strength of association between these serum proteins, and to determine group sizes needed for a high probability (80% power) of detecting statistical significance for 25% or 50% differences between typical PD and control subjects for these measurements. Analysis of log-transformed data found no statistically significant differences between groups for either α-synuclein or its antibodies. The concentrations of these proteins were weakly correlated (Spearman rho=0.16). In subjects with typical PD and atypical Parkinson syndromes, anti-α-synuclein antibody levels above 1.5 µg/ml were detected only in subjects with no more than four years of clinical disease. Power analysis indicated that 236 and 73 samples per group would be required for an 80% probability that 25% and 50% differences, respectively, in mean α-synuclein levels between typical PD and control subjects would be statistically significant; for anti-α-synuclein antibodies, 283 and 87 samples per group would be required. Our findings are consistent with those previous studies which suggested that serum concentrations of α-synuclein and its antibodies are not significantly altered in PD

ELISA measurement of specific non-antigen-bound antibodies to Aβ1-42 monomer and soluble oligomers in sera from Alzheimer's disease, mild cognitively impaired, and noncognitively impaired subjects

<p>Abstract</p> <p>Background</p> <p>The literature contains conflicting results regarding the status of serum anti-Aβ antibody concentrations in Alzheimer's disease (AD). Reduced levels of these antibodies have been suggested to contribute to the development of this disorder. The conflicting results may be due to polyvalent antibodies, antibody "masking" due to Aβ binding, methodological differences, and/or small sample sizes. The objectives of this pilot study were to compare serum anti-Aβ antibody concentrations between AD, mild cognitive impairment (MCI), and elderly noncognitively impaired (NCI) subjects while addressing these issues, and to perform power analyses to determine appropriate group sizes for future studies employing this approach.</p> <p>Methods</p> <p>Serum antibodies to Aβ1-42 monomer and soluble oligomers in AD, MCI, and NCI subjects (10/group) were measured by ELISA, subtracting polyvalent antibody binding and dissociating antibody-antigen complexes. Differences in mean antibody levels were assessed for significance with repeated measures ANOVA using restricted maximum likelihood estimation, using Tukey-Kramer tests and confidence intervals for multiple comparisons. Spearman's rank correlation was used to determine associations between anti-monomer and anti-oligomer antibody concentrations. Estimated sample sizes required to detect effects of various sizes were calculated.</p> <p>Results</p> <p>There were no significant differences between groups for mean anti-Aβ antibody levels, although these tended to be higher in AD than NCI specimens. Estimated group sizes of 328 and 150 for anti-Aβ monomer and oligomer antibodies, respectively, would have been required for 80% power for significance at 0.05 for a 25% increase in the AD mean relative to the NCI mean. Serum antibody concentrations to Aβ monomer and oligomers were strongly associated (correlations: 0.798 for undissociated sera, 0.564 for dissociated sera). Antibody-antigen dissociation significantly increased anti-Aβ monomer but not anti-Aβ oligomer antibody levels.</p> <p>Conclusions</p> <p>The findings in this pilot study are consistent with relatively similar concentrations of specific, non-antigen-bound antibodies to Aβ1-42 monomer and soluble oligomers in AD, MCI, and NCI sera. The differences between groups for these antibodies would have required approximate group sizes of 328 and 150, respectively, for a high probability for statistical significance. These findings do not support the hypothesis that reduced levels of anti-Aβ antibodies might contribute to AD's pathogenesis.</p

Anti-α-synuclein IgG concentrations in subjects with typical Parkinson’s disease and atypical Parkinson syndromes appear to decline with increased duration of clinical disease.

<p>Antibody concentrations above 1.5 µg/ml were only found in subjects with disease duration ≤ four years. (Diamonds = atypical Parkinson syndromes [APS]; circles = typical Parkinson’s disease [PD]).</p

Subject demographic data.

<p>Subject age, which was relatively normally distributed, is shown as mean±SD, together with age range. Gender is summarized as the percentage of male subjects in each group. Data for disease duration and Parkinson rating scales are presented as median and range because of the skewed nature of their distributions. Statistical comparisons relating to disease duration and Parkinson's disability scales were performed only between PD and APS patients. (RBD = rapid eye movement sleep behavior disorder; APS = atypical Parkinson syndromes; PD = typical Parkinson’s disease; CTL = clinically normal controls; UPDRS = Unified Parkinson’s Disease Rating Scale; NA = not applicable;</p>a<p>p<0.05 vs. subjects with PD).</p

PD serum and plasma α-synuclein measurements: previous studies.

<p>PD serum and plasma α-synuclein measurements: previous studies.</p