Are tangles as toxic as they look?

Neurofibrillary tangles are intracellular accumulations of hyperphosphorylated and misfolded tau protein characteristic of Alzheimer's disease and other tauopathies. Classic cross-sectional studies of Alzheimer patient brains showed associations of tangle accumulation with neuronal loss, synapse loss, and dementia, which led to the supposition that tangles are toxic to neurons. More recent advances in imaging techniques and mouse models have allowed the direct exploration of the question of toxicity of aggregated versus soluble tau and have surprisingly challenged the view of tangles as toxic species in the brain. Here, we review these recent experiments on the nature of the toxicity of tau with particular emphasis on our experiments imaging tangles in the intact brain through a cranial window, which allows observation of tangle formation and longitudinal imaging of the fate of tangle-bearing neurons. Neurofibrillary tangles (NFT) were first described in 1906 by Alois Alzheimer based on Bielschowsky silver staining of the brain of his demented patient Auguste D (Alzheimer 1907; Goedert and Spillantini 2006). These intraneuronal aggregates have subsequently been found to be composed primarily of hyperphosphorylated tau protein and are definitive pathological lesions not only in Alzheimer's disease but also in a class of neurodegenerative tauopathies (Goedert et al. 1988; Spires-Jones et al. 2009). NFT pathology in Alzheimer's disease (AD) correlates closely with cognitive decline and synapse and neuronal loss (Braak and Braak 1997; Bretteville and Planel 2008; Congdon and Duff 2008; Mocanu et al. 2008b; Spires-Jones et al. 2009). As a result, NFT have long been considered indicative of impending neuronal cell death. More recent evidence, however, opposes this classical view. Here we review evidence addressing the question of whether NFT cause structural or functional neuronal damage

Bathing Activities and Microbiological River Water Quality in the Paris Area: A Long-Term Perspective

This chapter presents the historical aspects regarding swimming in rivers in the Paris region since the seventeenth century, including the concept of fecal contamination indicator bacteria (FIBs) developed at the very beginning of the twentieth century, and historical contamination data covering more than one century in the Paris agglomeration. The sources of microbiological contamination of river waters are quantified, showing the importance of rain events. The present contamination levels are presented with reference to the European Directive for bathing water quality. FIB levels show that the sufficient quality for bathing is not reached yet in any of the monitored stations. A comprehensive data set regarding waterborne pathogens (viruses, Giardia, Cryptosporidium) in the Seine and Marne rivers is presented as a necessary complement to the regulatory FIB data to better evaluate health risks. The last section concludes on the actions to be conducted to improve the rivers’ microbiological quality in the coming years.info:eu-repo/semantics/publishe