Total and phosphorylated tau proteins: Evaluation as core biomarker candidates in frontotemporal dementia

An ever increasing number of patients with neurodegenerative disorders calls for the evaluation of potential diagnostic markers that allow an early diagnosis and an early initiation of specific therapy. Clinical diagnosis of Alzheimer's disease (AD), the most common neurodegenerative disorder, reaches 80-90% accuracy upon autopsy in specialized clinical centers. Diagnosis of AD in early clinical or preclinical stages is far less accurate, as is the differential diagnosis between AD and other primary dementias, such as frontotemporal dementia (FTD). Microtubule-associated tau protein is abnormally phosphorylated in AD and aggregates as paired helical filaments in neurofibrillary tangles. Recently, immunoassays have been developed detecting tau phosphorylated at specific epitopes in cerebrospinal fluid (CSF). Four years of clinical research consistently demonstrate that CSF phosphorylated tau (p-tau) is highly increased in AD compared to healthy controls and may differentiate AD from its most relevant differential diagnoses. Tau phosphorylated at threonine 231 (p-tau(231)) shows excellent differentiation between AD and FTD, whereas serine 181 (p-tau(181)) enhances accurate differentiation between AD and dementia with Lewy bodies. Moreover, p-tau(231) levels decline with disease progression, correlating with cognitive performance at baseline. Total tau (t-tau) is regarded as a general marker of neurodegeneration for evaluation in future population-based studies. p-tau(231) and p-tau(181) yield excellent discrimination between AD and non-AD dementias including FTD, exceeding the differential diagnostic and prognostic accuracy of t-tau. Therefore, p-tau is a core biological marker candidate for future evaluation in large national and international multicenter networks. Copyright (C) 2004 S. Karger AG, Basel

Early changes in alpha band power and DMN BOLD activity in Alzheimer's disease: a simultaneous resting state EEG-fMRI study

Simultaneous resting state functional magnetic resonance imaging (rsfMRI)-resting state electroencephalography (rsEEG) studies in healthy adults showed robust positive associations of signal power in the alpha band with BOLD signal in the thalamus, and more heterogeneous associations in cortical default mode network (DMN) regions. Negative associations were found in occipital regions. In Alzheimer's disease (AD), rsfMRI studies revealed a disruption of the DMN, while rsEEG studies consistently reported a reduced power within the alpha band. The present study is the first to employ simultaneous rsfMRI-rsEEG in an AD sample, investigating the association of alpha band power and BOLD signal, compared to healthy controls (HC). We hypothesized to find reduced positive associations in DMN regions and reduced negative associations in occipital regions in the AD group. Simultaneous resting state fMRI-EEG was recorded in 14 patients with mild AD and 14 HC, matched for age and gender. Power within the EEG alpha band (8-12 Hz, 8-10 Hz, and 10-12 Hz) was computed from occipital electrodes and served as regressor in voxel-wise linear regression analyses, to assess the association with the BOLD signal. Compared to HC, the AD group showed significantly decreased positive associations between BOLD signal and occipital alpha band power in clusters in the superior, middle and inferior frontal cortex, inferior temporal lobe and thalamus (p < 0.01, uncorr., cluster size ≥ 50 voxels). This group effect was more pronounced in the upper alpha sub-band, compared to the lower alpha sub-band. Notably, we observed a high inter-individual heterogeneity. Negative associations were only reduced in the lower alpha range in the hippocampus, putamen and cerebellum. The present study gives first insights into the relationship of resting-state EEG and fMRI characteristics in an AD sample. The results suggest that positive associations between alpha band power and BOLD signal in numerous regions, including DMN regions, are diminished in AD

Rheology of suspensions with aluminum nano-particles

Nano-scale aluminum particles are innovative materials increasingly used in energetic formulations. In this contribution, the rheological behavior of suspensions with either paraffin oil or HTPB as the matrix fluid and nano-scale aluminum (ALEX) as the dispersed phase is described and discussed. The paraffin oil/aluminum suspensions exhibit non-Newtonian flow behavior over a wide range of concentrations, whereas the HTPB/aluminum suspensions exhibitNewtonian behavior (i.e. the viscosity is independent of shear stress) up to a concentration of 50 vol.% aluminum. Both systems have unusual viscoelastic properties in that their elastic moduli are independent of the solids concentration

Measuring cortical connectivity in Alzheimer's disease as a brain neural network pathology: Toward clinical applications

Objectives: The objective was to review the literature on diffusion tensor imaging as well as resting-state functional magnetic resonance imaging and electroencephalography (EEG) to unveil neuroanatomical and neurophysiological substrates of Alzheimer’s disease (AD) as a brain neural network pathology affecting structural and functional cortical connectivity underlying human cognition. Methods: We reviewed papers registered in PubMed and other scientific repositories on the use of these techniques in amnesic mild cognitive impairment (MCI) and clinically mild AD dementia patients compared to cognitively intact elderly individuals (Controls). Results: Hundreds of peer-reviewed (cross-sectional and longitudinal) papers have shown in patients with MCI and mild AD compared to Controls (1) impairment of callosal (splenium), thalamic, and anterior–posterior white matter bundles; (2) reduced correlation of resting state blood oxygen level-dependent activity across several intrinsic brain circuits including default mode and attention-related networks; and (3) abnormal power and functional coupling of resting state cortical EEG rhythms. Clinical applications of these measures are still limited. Conclusions: Structural and functional (in vivo) cortical connectivity measures represent a reliable marker of cerebral reserve capacity and should be used to predict and monitor the evolution of AD and its relative impact on cognitive domains in pre-clinical, prodromal, and dementia stages of AD. (JINS, 2016, 22, 138–163

Use of nonintrusive sensor-based information and communication technology for real-world evidence for clinical trials in dementia

Cognitive function is an important end point of treatments in dementia clinical trials. Measuring cognitive function by standardized tests, however, is biased toward highly constrained environments (such as hospitals) in selected samples. Patient-powered real-world evidence using information and communication technology devices, including environmental and wearable sensors, may help to overcome these limitations. This position paper describes current and novel information and communication technology devices and algorithms to monitor behavior and function in people with prodromal and manifest stages of dementia continuously, and discusses clinical, technological, ethical, regulatory, and user-centered requirements for collecting real-world evidence in future randomized controlled trials. Challenges of data safety, quality, and privacy and regulatory requirements need to be addressed by future smart sensor technologies. When these requirements are satisfied, these technologies will provide access to truly user relevant outcomes and broader cohorts of participants than currently sampled in clinical trials

Certification of Cobalt in a Nickel Metal Reference Material for Neutron Dosimetry IRMM-521R

This certification report describes the processing and characterisation of IRMM 521R, a certified reference material (CRM) consisting of a high purity nickel foil with a cobalt content of < 0.26 mg/kg. With a 95 % probability, the cobalt content of samples of IRMM-521R is below this level. The certified level is sufficiently low to make the CRM fit for neutron dosimetry applications. Users of IRMM-521R avoid spectral interference due to cobalt impurities, thus reducing the uncertainty of their dosimetry measurements.JRC.D.2-Reference material

A strategy to determine DEM parameters for spherical and non-spherical particles

In Discrete element method (DEM) simulations the choice of appropriate contact parameters is significant to obtain reasonable results. Particularly, for the determination of DEM parameters for non-spherical particles a general straightforward procedure is not available. Therefore, in a first step of the investigation here, methods to obtain the friction and restitution coefficients experimentally for single particles [Polyoxymethylene (POM) spheres and quartz gravel] will be introduced. In the following, these predetermined DEM coefficients are used as initial values for the adjustment of bulk simulations to respective experiments. In the DEM simulations, the quartz gravel particles are represented by non-spherical particles approximated by clustered spheres. The best fit approximation of the non-spherical particles is performed automatically by a genetic algorithm. In order to optimize the sliding and rolling friction coefficients for DEM simulations, the static and dynamic angle of repose are determined from granular piles obtained by slump tests and rotating drum experiments, respectively. Additionally, a vibrating plate is used to obtain the dynamic bed height which is mainly influenced by the coefficient of restitution. The adjustment of the results of the bulk simulations to the experiments is conducted automatically by an optimization tool based on a genetic algorithm. The obtained contact parameters are later used to perform batch-screening DEM simulations and lead to accurate results. This underlines the applicability of the in parts automated strategy to obtain DEM parameters for particulate processes like screening.DFG, SPP 1679, Dynamische Simulation vernetzter Feststoffprozess