Extracellular accumulation of Aβ in β-amyloid plaques is thought to be associated with the neurodegeneration observed in Alzheimer’s disease (AD) patients, although a lack of correlation with cognitive decline raised doubts on this hypothesis. In different transgenic mouse models Aβ accumulates inside the cells and mice develop behavioral deficits well before visible extracellular β-amyloid accumulation. Here we show that intracellular Aβ accumulates in flotillin-1 positive endocytic vesicles. We also demonstrate that flotillin-1 is not only associated with intracellular Aβ in transgenic mice but also with extracellular β-amyloid plaques in AD patient brain sections. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Extracellular accumulation of Aβ in β-amyloid plaques is thought to be associated with the neurodegeneration observed in Alzheimer’s disease (AD) patients, although a lack of correlation with cognitive decline raised doubts on this hypothesis. In different transgenic mouse models Aβ accumulates inside the cells and mice develop behavioral deficits well before visible extracellular β-amyloid accumulation. Here we show that intracellular Aβ accumulates in flotillin-1 positive endocytic vesicles. We also demonstrate that flotillin-1 is not only associated with intracellular Aβ in transgenic mice but also with extracellular β-amyloid plaques in AD patient brain sections. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

This by-practice project is the first to provide an extensive investigation of the marginalisation of era appropriate science (EAS) and professional investigators by detective and historical detective fiction authors. The purpose of the thesis is to analyse specific detective fiction authors from the earliest formats of the nineteenth century through to the 1990s and contemporary, selected historical detective fiction authors. Its aim is to examine the creation, development and perpetuation of the marginalisation tradition. This generic trend can be read as the authors privileging their detective’s innate skillset, metonymic connectivity and deductive abilities, while underplaying and belittling EAS and professional investigators. Chapter One establishes the project’s critique of the generic trend by considering parental authors, E. T. A Hoffmann, Edgar Allan Poe, Émile Gaboriau and Wilkie Collins. Reading how these authors instigated and purposed the downplaying demonstrates its founding within detective fiction at the earliest point. By comparing how the authors sidelined and omitted specific EAS and professional investigators, alongside science available at the time, this thesis provides a framework for examining how it continued in detective fiction. In following chapters, the framework established in Chapter One and the theoretical views of Charles Rzepka, Lee Horsley, Stephen Knight and Martin Priestman, are used to discuss how minimising EAS and professional investigators developed into a tradition; and became a generic trend in the recognised detective fiction formula that was used by Sir Arthur Conan Doyle, Freeman Wills Crofts, H. C. Bailey, R. Austin Freeman, Agatha Christie, Ruth Rendell and P. D. James. I then examine how the device transferred to historical detective fiction, using the framework to consider Ellis Peters, Umberto Eco and other selected contemporary authors of historical detective fiction. Throughout, the critical aspect considers how the trivialisation developed and perpetuated through a generic trend. The research concludes that there is a trend embedded within detective and historical detective fiction. One that was created, developed and perpetuated by authors to augment their fictional detective’s innate skillset and to help produce narratives using it is a creative process. It further concludes that the trend can be reimagined to plausibly use EAS and professional investigators in detective and historical detective fiction. The aim of the creative aspect of the project is to employ the research and demonstrate how the tradition can be successfully reinterpreted. To do so, the historical detective fiction novel A Hidden Life uses traditional features of the detective fiction formula to support and strengthen plausible EAS and professional investigators within the narrative. The end result is a historical detective fiction novel. One that proves the thesis conclusion and is fundamentally crafted by the critical research.