A5049071884- Alzheimer's disease research and treatments
- Optical Coherence Tomography Applications
- Advanced Fluorescence Microscopy Techniques
- Prion Diseases and Protein Misfolding
- Neuroinflammation and Neurodegeneration Mechanisms
- Photoacoustic and Ultrasonic Imaging
- Mesenchymal stem cell research
- Cell Image Analysis Techniques
- Gut microbiota and health
- Cholinesterase and Neurodegenerative Diseases
- Neurological diseases and metabolism
- Tryptophan and brain disorders
- Neurological Disease Mechanisms and Treatments
- Glioma Diagnosis and Treatment
- Nicotinic Acetylcholine Receptors Study
- Protein Hydrolysis and Bioactive Peptides
- Memory and Neural Mechanisms
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Neuroscience and Neuropharmacology Research
- Barrier Structure and Function Studies
- Dementia and Cognitive Impairment Research
- Drug Transport and Resistance Mechanisms
- MicroRNA in disease regulation
- Parasite Biology and Host Interactions
- Epigenetics and DNA Methylation
International Flame Research Foundation
2016
University Hospital of Geneva
2016
University of Geneva
2016
Casa di Cura San Michele
2016
Azienda Ospedaliera Ospedale Maggiore
2016
École Polytechnique Fédérale de Lausanne
2012-2016
University of Brescia
2016
University Hospital of Zurich
2012
University of Tübingen
2006-2012
Hertie Institute for Clinical Brain Research
2006-2012
Protein aggregation is an established pathogenic mechanism in Alzheimer's disease, but little known about the initiation of this process vivo. Intracerebral injection dilute, amyloid-beta (Abeta)-containing brain extracts from humans with disease or beta-amyloid precursor protein (APP) transgenic mice induced cerebral beta-amyloidosis and associated pathology APP a time- concentration-dependent manner. The seeding activity was reduced abolished by Abeta immunodepletion, denaturation,...
Abstract Alzheimer’s disease is the most common form of dementia in western world, however there no cure available for this devastating neurodegenerative disorder. Despite clinical and experimental evidence implicating intestinal microbiota a number brain disorders, its impact on not known. To end we sequenced bacterial 16S rRNA from fecal samples Aβ precursor protein (APP) transgenic mouse model found remarkable shift gut as compared to non-transgenic wild-type mice. Subsequently generated...
Microglial cells aggregate around amyloid plaques in Alzheimer's disease, but, despite their therapeutic potential, various aspects of reactive kinetics and role plaque pathogenesis remain hypothetical. Through use vivo imaging quantitative morphological measures transgenic mice, we demonstrate that local resident microglia rapidly react to formation by extending processes subsequently migrating toward plaques, which individual transformed somata spatially stable for weeks. The number...
Molecular probes for selective identification of protein aggregates are important to advance our understanding the molecular pathogenesis underlying cerebral amyloidoses. Here we report chemical design pentameric thiophene derivatives, denoted luminescent conjugated oligothiophenes (LCOs), which could be used real-time visualization in transgenic mouse models neurodegenerative diseases by multiphoton microscopy. One LCOs, p-FTAA, utilized ex vivo spectral assignment distinct prion deposits...
Despite the importance of aberrant polymerization Abeta in early pathogenic cascade Alzheimer's disease, little is known about induction aggregation vivo. Here we show that cerebral beta-amyloidosis can be achieved many different brain areas APP23 transgenic mice through injection dilute Abeta-containing extracts. Once amyloidogenic process has been exogenously induced, nature induced Abeta-deposition determined by region host. Because these observations are reminiscent a prion-like...
Alzheimer's disease presents morphologically with senile plaques, primarily made of extracellular amyloid-β (Aβ) deposits, and neurofibrillary lesions, which consist intracellular aggregates hyperphosphorylated tau protein. To study the in vivo induction pathology, dilute brain extracts from aged Aβ-depositing APP23 transgenic mice were intracerebrally infused young B6/P301L mice. Six months after infusion, pathology was induced injected hippocampus but also regions well beyond injection...
In Alzheimer's disease, microglia cluster around beta-amyloid deposits, suggesting that these cells are important for amyloid plaque formation, maintenance and/or clearance. We crossed two distinct APP transgenic mouse strains with CD11b-HSVTK mice, in which nearly complete ablation of was achieved up to 4 weeks after ganciclovir application. Neither formation and nor amyloid-associated neuritic dystrophy depended on the presence microglia.
We demonstrate label-free imaging of cerebral β-amyloidosis ex vivo and in a living mouse model Alzheimer's disease using extended-focus Fourier domain optical coherence microscopy (xfOCM). xfOCM provides 3D, high-resolution images individual β-amyloid plaques the brain parenchyma vasculature requires no staining alzheimeric sample under investigation. also opens possibility to perform minimally invasive studies pathology vivo, without use labeling methods, which potentially confound...
Optical coherence tomography (OCT) and optical microscopy (OCM) allow the acquisition of quantitative three-dimensional axial flow by estimating Doppler shift caused moving scatterers.Measuring velocity red blood cells is currently principal application these methods.In many biological tissues, often perpendicular to axis, creating need for a measurement lateral flow.Previous work has shown that can be measured from bandwidth, albeit only simplified systems.In this work, we present...
Quantitative three-dimensional blood flow imaging is a valuable technique to investigate the physiology of brain. Two-photon microscopy (2PM) allows quantification local velocity with micrometric resolution by performing repeated line scans, but prohibitively long measurement times would be required apply this full volumes. By multiplexing image acquisition over depth, Fourier domain optical coherence tomography (FDOCT) enables velocities high volume rate, albeit at relatively low spatial...
Alzheimer's disease is the most common form of dementia in western world, however there no cure available for this devastating neurodegenerative disorder. Despite clinical and experimental evidence implicating intestinal microbiota a number brain disorders, its impact on not known. We generated germ-free mouse model discovered drastic reduction cerebral Ab amyloid pathology when compared to control animals with microbiota. Sequencing bacterial 16S rRNA from fecal samples revealed remarkable...
Intracerebral experimental gliomas attract intravenously injected murine or human bone marrow–derived hematopoietic progenitor and stem cells (HPC) in vitro, ex vivo, indicating that these might be suitable vehicles for a cell-based delivery of therapeutic molecules to malignant gliomas. With regard application, it is important investigate cell fates vivo (i.e., the time-dependent intratumoral systemic distribution after injection). Conventional histological analysis has limitations this...
Functional magnetic resonance (fMRI) imaging is the current gold-standard in neuroimaging. fMRI exploits local changes blood oxygenation to map neuronal activity over entire brain. However, its spatial resolution currently limited a few hundreds of microns. Here we use extended-focus optical coherence microscopy (xfOCM) quantitatively measure flow velocity during functional hyperaemia at high spatio-temporal somatosensory cortex mice. As acquires depth slices simultaneously, measurements can...
Alzheimer's disease (AD) is a complex pathology of the central nervous system characterized by degradation cognitive abilities due to detrimental effects Abeta aggregates/oligomers and formation neurofibrillary tau tangles. Most experimental therapies clinical efforts currently under development target either or proteins with high specificity. Stem cells might be novel multi-target approach tackle AD. Human safety intravenous(IV) administration ischemia tolerant mesenchymal stem cells(itMSC)...
β-Amyloid plaques are a major hallmark of Alzheimer's disease (AD). These plaque deposits invariably accompanied by an inflammatory reaction involving microglia, which the primary immune effector cells brain. It is known that microglia attracted to and surround amyloid in transgenic mice AD brains. Microglia have been suggested be involved formation, maintenance phagocytosis. To study effect cerebral amyloidosis, we crossed CD11b-HSVTK (TK mice) with APPPS1 mice. TK allow depletion upon...
We review optical coherence microscopy and present selected structural functional imaging applications ranging from diabetes to brain imaging, including new concepts for cell with an emphasis on the underlying concepts.
Alzheimer's disease (AD) is a neurodegenerative disorder pathologically characterized by the formation of extracellular senile plaques, primarily composed aggregated amyloid-beta (Abeta) peptides. Today, brain imaging an established method for AD drug discovery in animal studies and clinical trials. Microscopy techniques such as two-photon microscopy, though invasive dependent on contrast agent, allow direct visualization with micrometric resolution individual amyloid main neuropathological...