Amyloid-beta oligomerization is associated with the generation of a typical peptide fragment fingerprint

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Application of anti-amyloid beta immunization using encapsulated cell technology in mouse models of Alzheimer's disease

Alzheimer's disease (AD) is the most common form of dementia in the elderly. AD is characterized by the deposition of two aggregated proteins: Amyloid beta (Aß) and hyperphosphorylated tau. Accumulations of these proteins are thought to be the signature ...

EPFL2019

Supervised learning to quantify amyloidosis in whole brains of an Alzheimer's disease mouse model acquired with optical projection tomography

Dimitri Nestor Alice Van De Ville, Theo Lasser, Aleksandra Radenovic, Paul James Marchand, Arielle Louise Planchette, Virginie Sophie Uhlmann, David Nguyen

Alzheimer's disease (AD) is characterized by amyloidosis of brain tissues. This phenomenon is studied with genetically-modified mouse models. We propose a method to quantify amyloidosis in whole 5xFAD mouse brains, a model of AD. We use optical projection ...

2019

The metalloprotease ADAMTS4 generates N-truncated A4-x species and marks oligodendrocytes as a source of amyloidogenic peptides in Alzheimer's disease

Patrick Fraering, Mitko Dimitrov, Hermeto Gerber, Sandra Lehmann

Brain accumulation and aggregation of amyloid- (A) peptides is a critical step in the pathogenesis of Alzheimer's disease (AD). Full-length A peptides (mainly A1-40 and A1-42) are produced through sequential proteolytic cleavage of the amyloid precursor pr ...

SPRINGER2019

GABA and glutamate moderate beta-amyloid related functional connectivity in cognitively unimpaired old-aged adults

Dimitri Nestor Alice Van De Ville, Maria Giulia Preti

Background: Effects of beta-amyloid accumulation on neuronal function precede the clinical manifestation of Alzheimer's disease (AD) by years and affect distinct cognitive brain networks. As previous studies suggest a link between beta-amyloid and dysregul ...

2019

Crosslinking Allosteric Sites on the Nucleosome Core Particle

Lucinda Kate Batchelor

Designing compounds that bind to the acidic patch of the nucleosome core particle (NCP) is an emerging therapeutic approach that can inhibit the binding of key chromatin factors. Pretreatment of human ovarian carcinoma, A2780, cells with RAPTA-T, an antime ...

EPFL2019

A viral vector based in vivo model of tauopathy to explore therapeutic strategies against tau pathology

Sameer Mohammad Khaleel Nazeeruddin

Tauopathies are neurodegenerative diseases whose common pathological feature is the intraneuronal accumulation of tau aggregates. Tau protein has various roles in the neuron, among which stabilization of microtubules (MT), regulation of synaptic activity o ...

EPFL2019

Development and performance evaluation of a high mass resolution time of flight laser ablation ionisation mass spectrometer

Reto Wiesendanger

This thesis contributes to the field of analytical chemistry of solid samples by introducing a new instrument with unprecedented performance characteristics and analytical capabilities. The instrument is based on the laser ablation and ionisation time-of-f ...

EPFL2019

Calpain-mediated tau fragmentation is altered in Alzheimer's disease progression

Andrea Pfeifer, Andreas Muhs

The aggregation of intracellular tau protein is a major hallmark of Alzheimer's disease (AD). The extent and the stereotypical spread of tau pathology in the AD brain are correlated with cognitive decline during disease progression. Here we present an in-d ...

Nature Research2018

Zinc and Copper Differentially Modulate Amyloid Precursor Protein Processing by -Secretase and Amyloid- Peptide Production

Patrick Fraering, Mitko Dimitrov, Hermeto Gerber, Guillermo Miguel Garcia Osuna

Recent evidence suggests involvement of biometal homeostasis in the pathological mechanisms in Alzheimer's disease (AD). For example, increased intracellular copper or zinc has been linked to a reduction in secreted levels of the AD-causing amyloid- peptid ...

Amer Soc Biochemistry Molecular Biology Inc2017

Reduction of Abeta amyloid pathology in APPPS1 transgenic mice in the absence of gut microbiota

Theo Lasser, Tristan Bolmont, Taoufiq Harach, Nicolas Jean Marc Antoine Duthilleul

Alzheimer’s disease is the most common form of dementia in the western world, however there is no cure available for this devastating neurodegenerative disorder. Despite clinical and experimental evidence implicating the intestinal microbiota in a number o ...

Nature Research2017

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