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

Threshold logic implementation of a modular computer system design

Threshold logic implementation for LSI design of modular computer syste

Kinematic analysis of handwriting movements in patients with Alzheimer's disease, mild cognitive impairment, depression and healthy subjects

A variety of studies have demonstrated that motor disorders, parkinsonism and extrapyramidal motor symptoms (EPMS) are common in patients with Alzheimer's disease (AD). Several studies have reported an association of EPMS with severity, progression and poor prognosis of AD. The majority of these studies used clinical assessments for the rating of EPMS. In this study, kinematic handwriting analysis was used to quantify differences in fine hand motor function in patients with probable AD and mild cognitive impairment (MCl, as an assumed initial stage of AD) compared to depressed patients and healthy controls. Both patients with MCl and patients with probable AD exhibited loss of fine motor performance. Movements of AD patients were significantly less regular than those of healthy controls. Copyright (C) 2003 S. Karger AG, Basel

Changes in marsh nekton communities along the salinity gradient of the river Schelde: preliminary results (poster)

In the salt marshes different habitats as well as the environmental parameters influence the composition of the nekton community. Considering both the environmental parameters and the different habitats, our sampling campaign occurred in five marshes along the River Schelde (Grembergen, Saeftinghe, Waarde, Zuidgors and Zwin). The salinity gradient differed from 0.2 till 29 psu. Sampling campaign occurred from April until October in 2000.Three different sampling techniques were used adapting to the different habitats. Fyke nets were set in the big creeks. Block net sampled the small creeks by closing the mouth of the creek at the moment of the high water and fish traps were placed into small ponds. Data analysis is still under progress but already remarkable differences were observed.The eel, Anguilla anguilla dominate the fish community in the fresh water marsh. This area is characterised by low catch.Mesohaline and oligohaline marshes are dominated by two fish species, Pleuronectes flesus and Dicentrarchus labrax. High catch of fyke net marks these marshes. In the small creeks, adult Palaemonetes varians and Pleuronectes flesus was captured by block net. Larvae of Pomatoschistus microps and adult Palaemonetes varians appeared in high number in the fish traps.Polyhaline marsh was characterised by low catch with all the different sampling techniques. Only the shore crab, Carcinus maenas was present in very high abundance in the creeks. But in the autumn high numbers of Pomatochistus microps were caught in the small channel

Habitat value of a developing estuarine brackish marsh

Marsh creation receives worldwide attention in mitigating loss of coastal wetlands and in management retreat of estuaries. In the Westerschelde, the former Selena Polder, south of "Het Verdronken Land van Saeftinghe", evolved into the Sieperda marsh after several dyke breaches. Soon after the tides regained access to the polder, a tidal creek was formed. Ten years after, a developing marsh system is found close to a mature marsh system. This situation offered the rare and unique opportunity to compare under similar circumstances the utilisation by nekton species of a natural mature marsh with a recently created developing marsh. Between April and October 1999 both the mature Saeftinghe marsh and the developing Sieperda marsh were sampled every six weeks on two consecutive days. Each sampling occasion covered the whole tidal cycle. The most important environmental parameters (water height, temperature, salinity, turbidity and dissolved oxygen) were similar in both marsh creeks. A distinct difference in nekton community structure between the two marshes was observed. Total biomass and densities of nekton species were remarkably higher in Saeftinghe. In Saeftinghe, a density peak occurred in July and was mainly due to large numbers of the mysids Neomysis integer. In Sieperda, peak densities in September were caused by high abundances of the mysids Mesopodopsis slabberi. This difference in species dominance was observed during all sampling occasions. Biomass peaked in July in the mature marsh and in October in the developing marsh. Mysid shrimp (Neomysis integer) and fish (mainly Pomatoschistus microps) were the main contributors to the biomass in the natural marsh. Herring, sprat (Clupeidae) and shore crab (Carcinus maenas) were more important in Sieperda. For Pomatoschistus microps, distinct differences in length-frequency distributions were noted between both marshes. While creek morphology plays an important role, the development stage of a marsh is believed to be a prime factor in determining the habitat function of creek systems of developing and mature marshes

Multiple blood-brain barrier transport mechanisms limit bumetanide accumulation, and therapeutic potential, in the mammalian brain

There is accumulating evidence that bumetanide, which has been used over decades as a potent loop diuretic, also exerts effects on brain disorders, including autism, neonatal seizures, and epilepsy, which are not related to its effects on the kidney but rather mediated by inhibition of the neuronal Na-K-C1 cotransporter isoform NKCC1. However, following systemic administration, brain levels of bumetanide are typically below those needed to inhibit NKCC1, which critically limits its clinical use for treating brain disorders. Recently, active efflux transport at the blood-brain barrier (BBB) has been suggested as a process involved in the low brain:plasma ratio of bumetanide, but it is presently not clear which transporters are involved. Understanding the processes explaining the poor brain penetration of bumetanide is needed for developing strategies to improve the brain delivery of this drug. In the present study, we administered probenecid and more selective inhibitors of active transport carriers at the BBB directly into the brain of mice to minimize the contribution of peripheral effects on the brain penetration of bumetanide. Furthermore, in vitro experiments with mouse organic anion transporter 3 (Oat3)-overexpressing Chinese hamster ovary cells were performed to study the interaction of bumetanide, bumetanide derivatives, and several known inhibitors of Oats on Oat3-mediated transport. The in vivo experiments demonstrated that the uptake and efflux of bumetanide at the BBB is much more complex than previously thought. It seems that both restricted passive diffusion and active efflux transport, mediated by Oat3 but also organic anion-transporting polypeptide (Oatp) Oatpla4 and multidrug resistance protein 4 explain the extremely low brain concentrations that are achieved after systemic administration of bumetanide, limiting the use of this drug for targeting abnormal expression of neuronal NKCC1 in brain diseases

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