IVIG Delays Onset in a Mouse Model of Gerstmann-Sträussler-Scheinker Disease

Our previous studies showed that intravenous immunoglobulin (IVIG) contained anti-Aβ autoantibodies that might be able to treat Alzheimer's disease (AD). Recently, we identified and characterized naturally occurring autoantibodies against PrP from IVIG. Although autoantibodies in IVIG blocked PrP fibril formation and PrP neurotoxicity in vitro, it remained unknown whether IVIG could reduce amyloid plaque pathology in vivo and be used to effectively treat animals with prion diseases. In this study, we used Gerstmann-Sträussler-Scheinker (GSS)-Tg (PrP-A116V) transgenic mice to test IVIG efficacy since amyloid plaque formation played an important role in GSS pathogenesis. Here, we provided strong evidence that demonstrates how IVIG could significantly delay disease onset, elongate survival, and improve clinical phenotype in Tg (PrP-A116V) mice. Additionally, in treated animals, IVIG could markedly inhibit PrP amyloid plaque formation and attenuate neuronal apoptosis at the age of 120 days in mice. Our results indicate that IVIG may be a potential, effective therapeutic treatment for GSS and other prion diseases

Comparing Clinical Profiles in Alzheimer\u27s Disease and Parkinson\u27s Disease Dementia

BACKGROUND: Greater understanding of differences in baseline impairment and disease progression in patients with Alzheimer\u27s disease (AD) and Parkinson\u27s disease dementia (PDD) may improve the interpretation of drug effects and the design of future studies. METHODS: This was a retrospective analysis of three randomized, double-blind rivastigmine databases (one in PDD, two in AD). Impairment on the Alzheimer\u27s Disease Assessment Scale-cognitive subscale (ADAS-cog), Alzheimer\u27s Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scale, 10-item Neuropsychiatric Inventory (NPI-10) and the ADCS-Clinical Global Impression of Change (CGIC) was compared [standardized difference (Cohen\u27s d), similar if \u3c0.1]. RESULTS: Patients with AD or PDD had similar levels of impairment on the ADAS-cog and NPI-10. Scores on the ADCS-ADL scale (standardized difference = 0.47) and the ADAS-cog memory domain (total, 0.33; items, 0.10-0.58) were higher in AD; PDD patients were more impaired in the language (0.23) and praxis (0.34) domains. AD patients receiving placebo showed greater deterioration on the ADAS-cog (0.14) and improvement on the NPI-10 (0.11) compared with patients with PDD. CONCLUSION: Differing patterns of impairment occur in AD and PDD

The Cognitive Change Index as a Measure of Self and Informant Perception of Cognitive Decline: Relation to Neuropsychological Tests

BACKGROUND: The perception of cognitive decline by individuals and those who know them well ("informants") has been inconsistently associated with objective cognitive performance, but strongly associated with depressive symptoms. OBJECTIVE: We investigated associations of self-report, informant-report, and discrepancy between self- and informant-report of cognitive decline obtained from the Cognitive Change Index (CCI) with cognitive test performance and self-reported depressive symptoms. METHODS: 267 participants with normal cognition, mild cognitive impairment (MCI), or mild dementia were included from a cohort study and memory clinic. Association of test performance and self-rated depression (Geriatric Depression Scale, GDS) with CCI scores obtained from subjects (CCI-S), their informants (CCI-I), and discrepancy scores between subjects and informants (CCI-D; CCI-S minus CCI-I) were analyzed using correlation and analysis of covariance (ANCOVA) models. RESULTS: CCI-S and CCI-I scores showed high internal consistency (Cronbach alpha 0.96 and 0.98, respectively). Higher scores on CCI-S and CCI-I, and lower scores on the CCI-D, were associated with lower performance on various cognitive tests in both univariate and in ANCOVA models adjusted for age, gender, and education. Adjustment for GDS slightly weakened the relationships between CCI and test performance but most remained significant. CONCLUSION: Self- and informant-report of cognitive decline, as measured by the CCI, show moderately strong relationships with objective test performance independent of age, gender, education, and depressive symptoms. The CCI appears to be a valid cross-sectional measure of self and informant perception of cognitive decline across the continuum of functioning. Studies are needed to address the relationship of CCI scores to longitudinal outcome

Intra-guild competition and its implications for one of the biggest terrestrial predators, Tyrannosaurus rex

Identifying tradeoffs between hunting and scavenging in an ecological context is important for understanding predatory guilds. In the past century, the feeding strategy of one of the largest and best-known terrestrial carnivores, Tyrannosaurus rex, has been the subject of much debate: was it an active predator or an obligate scavenger? Here we look at the feasibility of an adult T. rex being an obligate scavenger in the environmental conditions of Late Cretaceous North America, given the size distributions of sympatric herbivorous dinosaurs and likely competition with more abundant small-bodied theropods. We predict that nearly 50 per cent of herbivores would have been within a 55–85 kg range, and calculate based on expected encounter rates that carcasses from these individuals would have been quickly consumed by smaller theropods. Larger carcasses would have been very rare and heavily competed for, making them an unreliable food source. The potential carcass search rates of smaller theropods are predicted to be 14–60 times that of an adult T. rex. Our results suggest that T. rex and other extremely large carnivorous dinosaurs would have been unable to compete as obligate scavengers and would have primarily hunted large vertebrate prey, similar to many large mammalian carnivores in modern-day ecosystems

Association of cerebrospinal fluid Aβ42 with A2M gene in cognitively normal subjects

Low cerebrospinal fluid (CSF) Aβ42 levels correlate with increased brain Aβ deposition in Alzheimer’s disease (AD), which suggests a disruption in the degradation and clearance of Aβ from the brain. In addition, APOE ε4 carriers have lower CSF Aβ42 levels than non-carriers. The hypothesis of this investigation was that CSF Aβ42 levels correlate with regulatory region variation in genes that are biologically associated with degradation or clearance of Aβ from the brain. CSF Aβ42 levels were tested for associations with Aβ degradation and clearance genes and APOE ε4. Twenty-four SNPs located within the 5′ and 3′ regions of 12 genes were analyzed. The study sample consisted of 99 AD patients and 168 cognitively normal control subjects. CSF Aβ42 levels were associated with APOE ε4 status in controls but not in AD patientsA2M regulatory region SNPs were also associated with CSF Aβ42 levels in controls, but not in AD patients, even after adjusting for APOE ε4. These results suggest that genetic variation within the A2M gene influences CSF Aβ42 levels

Neither bones nor feet: track morphological variation and “preservation quality”

As purely sedimentary structures, fossil footprints are all about shape. Correctly interpreting the significance of their surface topography requires understanding the sources of morphological variation. Differences among specimens are most frequently attributed to either taxonomy (trackmaker) or to preservation quality. “Well-preserved” tracks are judged more similar to pedal anatomy than “poorly preserved” ones, but such broad-brush characterizations confound two separate episodes in a track’s history. Current evaluations of track quality fail to distinguish among behavioral, formational, intravolumetric, and post-formational sources of variation. Based on analogy with body fossils, we recommend restricting assessments of track preservation quality to modifications that take place only after a track is created. Ichnologists need to try to parse the relative influence of factors affecting disparity, but we currently lack an adequate vocabulary to describe the overall shapes and specific features of formational variants

Cognitive complaints in older adults at risk for Alzheimer's disease are associated with altered resting-state networks

INTRODUCTION: Pathophysiological changes that accompany early clinical symptoms in prodromal Alzheimer's disease (AD) may have a disruptive influence on brain networks. We investigated resting-state functional magnetic resonance imaging (rsfMRI), combined with brain connectomics, to assess changes in whole-brain functional connectivity (FC) in relation to neurocognitive variables. METHODS: Participants included 58 older adults who underwent rsfMRI. Individual FC matrices were computed based on a 278-region parcellation. FastICA decomposition was performed on a matrix combining all subjects' FC. Each FC pattern was then used as a response in a multilinear regression model including neurocognitive variables associated with AD (cognitive complaint index [CCI] scores from self and informant, an episodic memory score, and an executive function score). RESULTS: Three connectivity independent component analysis (connICA) components (RSN, VIS, and FP-DMN FC patterns) associated with neurocognitive variables were identified based on prespecified criteria. RSN-pattern, characterized by increased FC within all resting-state networks, was negatively associated with self CCI. VIS-pattern, characterized by an increase in visual resting-state network, was negatively associated with CCI self or informant scores. FP-DMN-pattern, characterized by an increased interaction of frontoparietal and default mode networks (DMN), was positively associated with verbal episodic memory. DISCUSSION: Specific patterns of FC were differently associated with neurocognitive variables thought to change early in the course of AD. An integrative connectomics approach relating cognition to changes in FC may help identify preclinical and early prodromal stages of AD and help elucidate the complex relationship between subjective and objective indices of cognitive decline and differences in brain functional organization

Regge behaviour of distribution functions and t and x-evolutions of gluon distribution function at low-x

In this paper t and x-evolutions of gluon distribution function from Dokshitzer-Gribov-Lipatov-Altarelli-Parisi(DGLAP) evolution equation in leading order(LO) at low-x, assuming the Regge behaviour of quark and gluon at this limit, are presented. We compare our results of gluon distribution function with MRST 2001, MRST 2004 and GRV '98 parameterizations and show the compatibility of Regge behaviour of quark and gluon distribution functions with perturbative quantum chromodynamics(PQCD) at low-x. We also discuss the limitations of Taylor series expansion method used earlier to solve DGLAP evolution equations, in the Regge behaviour of distribution functions.Comment: 19 pages, 7 figure