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

Age-dependent differences in human brain activity using a face- and location-matching task: An fMRI study

Purpose: To evaluate the differences of cortical activation patterns in young and elderly healthy subjects for object and spatial visual processing using a face- and location-matching task. Materials and Methods: We performed a face- and a location-matching task in 15 young (mean age: 28 +/- 9 years) and 19 elderly (mean age: 71 +/- 6 years) subjects. Each experiment consisted of 7 blocks alternating between activation and control condition. For face matching, the subjects had to indicate whether two displayed faces were identical or different. For location matching, the subjects had to press a button whenever two objects had an identical position. For control condition, we used a perception task with abstract images. Functional imaging was performed on a 1.5-tesla scanner using an EPI sequence. Results: In the face-matching task, the young subjects showed bilateral (right 1 left) activation in the occipito-temporal pathway (occipital gyrus, inferior and middle temporal gyrus). Predominantly right hemispheric activations were found in the fusiform gyrus, the right dorsolateral prefrontal cortex (inferior and middle frontal gyrus) and the superior parietal gyrus. In the elderly subjects, the activated areas in the right fronto-lateral cortex increased. An additional activated area could be found in the medial frontal gyrus (right > left). In the location-matching task, young subjects presented increased bilateral (right > left) activation in the superior parietal lobe and precuneus compared with face matching. The activations in the occipito-temporal pathway, in the right fronto-lateral cortex and the fusiform gyrus were similar to the activations found in the face-matching task. In the elderly subjects, we detected similar activation patterns compared to the young subjects with additional activations in the medial frontal gyrus. Conclusion: Activation patterns for object-based and spatial visual processing were established in the young and elderly healthy subjects. Differences between the elderly and young subjects could be evaluated, especially by using a face-matching task. Copyright (c) 2007 S. Karger AG, Basel

Highly Sensitive Gamma-Spectrometers of GERDA for Material Screening: Part 2

The previous article about material screening for GERDA points out the importance of strict material screening and selection for radioimpurities as a key to meet the aspired background levels of the GERDA experiment. This is directly done using low-level gamma-spectroscopy. In order to provide sufficient selective power in the mBq/kg range and below, the employed gamma-spectrometers themselves have to meet strict material requirements, and make use of an elaborate shielding system. This article gives an account of the setup of two such spectrometers. Corrado is located in a depth of 15 m w.e. at the MPI-K in Heidelberg (Germany), GeMPI III is situated at the Gran-Sasso underground laboratory at 3500 m w.e. (Italy). The latter one aims at detecting sample activities of the order ~0.01 mBq/kg, which is the current state-of-the-art level. The applied techniques to meet the respective needs are discussed and demonstrated by experimental results.Comment: Featured in: Proceedings of the XIV International Baksan School "Particles and Cosmology" Baksan Valley, Kabardino-Balkaria, Russia, April 16-21,2007. INR RAS, Moscow 2008. ISBN 978-5-94274-055-9, pp. 233-238; (6 pages, 4 figures

Proteome-based plasma biomarkers for Alzheimer's disease

Alzheimer's disease is a common and devastating disease for which there is no readily available biomarker to aid diagnosis or to monitor disease progression. Biomarkers have been sought in CSF but no previous study has used two-dimensional gel electrophoresis coupled with mass spectrometry to seek biomarkers in peripheral tissue. We performed a case-control study of plasma using this proteomics approach to identify proteins that differ in the disease state relative to aged controls. For discovery-phase proteomics analysis, 50 people with Alzheimer's dementia were recruited through secondary services and 50 normal elderly controls through primary care. For validation purposes a total of 511 subjects with Alzheimer's disease and other neurodegenerative diseases and normal elderly controls were examined. Image analysis of the protein distribution of the gels alone identifies disease cases with 56% sensitivity and 80% specificity. Mass spectrometric analysis of the changes observed in two-dimensional electrophoresis identified a number of proteins previously implicated in the disease pathology, including complement factor H (CFH) precursor and α-2-macroglobulin (α- 2M). Using semi-quantitative immunoblotting, the elevation of CFH and α- 2M was shown to be specific for Alzheimer's disease and to correlate with disease severity although alternative assays would be necessary to improve sensitivity and specificity. These findings suggest that blood may be a rich source for biomarkers of Alzheimer's disease and that CFH, together with other proteins such as α- 2M may be a specific markers of this illness. © 2006 The Author(s).link_to_subscribed_fulltex

Complete results for five years of GNO solar neutrino observations

We report the complete GNO solar neutrino results for the measuring periods GNO III, GNO II, and GNO I. The result for GNO III (last 15 solar runs) is [54.3 + 9.9 - 9.3 (stat.)+- 2.3 (syst.)] SNU (1 sigma) or [54.3 + 10.2 - 9.6 (incl. syst.)] SNU (1 sigma) with errors combined. The GNO experiment is now terminated after altogether 58 solar exposure runs that were performed between May 20, 1998 and April 9, 2003. The combined result for GNO (I+II+III) is [62.9 + 5.5 - 5.3 (stat.) +- 2.5 (syst.)] SNU (1 sigma) or [62.9 + 6.0 - 5.9] SNU (1 sigma) with errors combined in quadrature. Overall, gallium based solar observations at LNGS (first in GALLEX, later in GNO) lasted from May 14, 1991 through April 9, 2003. The joint result from 123 runs in GNO and GALLEX is [69.3 +- 5.5 (incl. syst.)] SNU (1 sigma). The distribution of the individual run results is consistent with the hypothesis of a neutrino flux that is constant in time. Implications from the data in particle- and astrophysics are reiterated.Comment: 22 pages incl. 9 Figures and 8 Tables. to appear in: Physics Letters B (accepted April 13, 2005) PACS: 26.65.+t ; 14.60.P

Characterization of the terminal column of TRIGA Mark II reactor of Mainz through of alanine pellets.

We have studied the ESR response of alanine pellets with and without gadolinium exposed to the thermal column of the TRIGA Mark II research reactor at the University of Mainz (Germany). The choice of Gd as additive nucleus is due to its very high capture cross section to thermal neutrons and to the possibility for secondary particles produced after interaction with thermal neutrons of releasing their energy in the neighborhood of the reaction site. In particular, it was found that low concentration (5% by weight) of Gd brings about a neutron sensitivity enhancement of more than 10 times without heavily reducing tissue equivalence. Monte Carlo (MC) simulations of both response of alanine and Gd-alanine pellets with FLUKA code were performed and the results were compared with the experimental values

Highly sensitive gamma-spectrometers of GERDA for material screening: Part I

The GERDA experiment aims to search for the neutrinoless double beta-decay of 76Ge and possibly for other rare processes. The sensitivity of the first phase is envisioned to be more than one order of magnitude better than in previous neutrinoless double beta-decay experiments. This implies that materials with ultra-low radioactive contamination need to be used for the construction of the detector and its shielding. Therefore the requirements on material screening include high-sensitivity low-background detection techniques and long measurement times. In this article, an overview of material-screening laboratories available to the GERDA collaboration is given, with emphasis on the gamma-spectrometry. Additionally, results of an intercomparison of the evaluation accuracy in these laboratories are presented.Comment: Featured in: Proceedings of the XIV International Baksan School "Particles and Cosmology" Baksan Valley, Kabardino-Balkaria, Russia, April 16-21,2007. INR RAS, Moscow 2008. ISBN 978-5-94274-055-9, pp. 228-232; (5 pages, 0 figures

Pictures of Synthetic Biology: A reflective discussion of the representation of Synthetic Biology (SB) in the German-language media and by SB experts

This article is concerned with the representation of Synthetic Biology in the media and by biotechnology experts. An analysis was made of German-language media articles published between 2004 and 2008, and interviews with biotechnology-experts at the Synthetic Biology conference SB 3.0 in Zurich 2007. The results have been reflected in terms of the definition of Synthetic Biology, applications of Synthetic Biology and the perspectives of opportunities and risks. In the media, Synthetic Biology is represented as a new scientific field of biology with an engineering-like thinking, while the scientists interviewed mostly define Synthetic Biology as contrary to nature and the natural system. Media articles present Synthetic Biology broadly with positive potential and inform the publics less about the potential risks than about the benefits of Synthetic Biology. In contrast, the experts interviewed reflect more on the risks than the opportunities of Synthetic Biology. Both used metaphors to describe Synthetic Biology and its aspects