About
35
Publications
3,144
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
1,672
Citations
Introduction
Additional affiliations
November 2014 - February 2016
October 2012 - April 2013
August 2007 - September 2012
Education
April 2005 - February 2007
October 1997 - November 2002
Publications
Publications (35)
Studying bacterial cell envelope architecture with electron microscopy is challenging due to the poor preservation of microbial ultrastructure with traditional methods. Here, we established and validated a super-resolution cryo-correlative light and electron microscopy (cryo-CLEM) method, and combined it with cryo-focused ion beam (cryo-FIB) millin...
This volume discusses different approaches to workflows for large volume electron microscopy - from preparation of samples to their imaging in a variety of microscopes - in some cases also applying correlative techniques. The chapters in this book cover topics such as correlative super resolution and electron microscopy to detect molecules in their...
Video S1. 3D-Reconstruction of the Axonal Network Facilitates Identification of Target Dendrite, Related to Figure 4
Video S3. High-Resolution FIB/SEM 3D-Reconstruction of a Single Tripartite Synapse, Related to Figure 5
Video S2. FIB/SEM 3D-Reconstruction of a Single Dendritic Element, Related to Figure 5
Emerging 3D correlative light and electron microscopy approaches enable studying neuronal structure-function relations at unprecedented depth and precision. However, established protocols for the correlation of light and electron micrographs rely on the introduction of artificial fiducial markers, such as polymer beads or near-infrared brandings, w...
Cognitive decline in Alzheimer's disease is attributed to loss of functional synapses, most likely caused by synaptotoxic, oligomeric forms of amyloid-beta. Many treatment options aim at reducing amyloid-beta levels in the brain, either by decreasing its production or by increasing its clearance. We quantified the effects of immunotherapy directed...
A major neuropathological hallmark of Alzheimer's disease is the deposition of amyloid plaques in the brains of affected individuals. Amyloid plaques mainly consist of fibrillar beta-amyloid, which is a cleavage product of the amyloid precursor protein. The amyloid-cascade-hypothesis postulates Abeta accumulation as the central event in initiating...
Unlabelled:
The progression of β-amyloid deposition in the brains of mice overexpressing Swedish mutant β-amyloid precursor protein (APP-Swe), a model of Alzheimer disease (AD), was investigated in a longitudinal PET study using the novel β-amyloid tracer (18)F-florbetaben.
Methods:
Groups of APP-Swe and age-matched wild-type (WT) mice (age rang...
Tauopathies are widespread neurodegenerative disorders characterised by the intracellular accumulation of hyperphosphorylated tau. Especially in Alzheimer's disease, pathological alterations in the retina are discussed as potential biomarkers to improve early diagnosis of the disease. Using mice expressing human mutant P301S tau, we demonstrate for...
FSB-positive cells are vital.
A–A'''' In P301S mice crossed with Thy1-YFPH, 1.9% of FSB-positive cells also contained YFP. No pathological alterations in the dendritic arbors of these cells could be observed. Shown is one co-labelled cell (FSB, AT8, and YFP) next to cells containing either YFP only or FSB and AT8 only. A x–y projection, A'''' x–z p...
Amyloid-beta plaque deposition represents a major neuropathological hallmark of Alzheimer’s disease. While numerous studies have described dendritic spine loss in proximity to plaques, much less is known about the kinetics of these processes. In particular, the question as to whether synapse loss precedes or follows plaque formation remains unanswe...
The in vivo diagnosis of Alzheimer's disease (AD) is of high socioeconomic interest and remains a demanding field of research. The biopathological hallmarks of the disease are extracellular plaques consisting of aggregated β-amyloid peptides (Aβ) and tau protein derived intracellular tangles. Here we report the synthesis and evaluation of fluoresce...
Bevacizumab targets VEGF-A and has proved beneficial in glioma patients, improving clinical symptoms by the reduction of tumor edema. However, it remains controversial whether or not bevacizumab exerts antitumor effects in addition to (and potentially independent of) its effects on tumor vessels, and it is unknown what doses are needed to achieve t...
The kinetics of amyloid plaque formation and growth as one of the characteristic hallmarks of Alzheimer’s disease (AD) are fundamental issues in AD research. Especially the question how fast amyloid plaques grow to their final size after they are born remains controversial. By long-term two-photon in vivo imaging we monitored individual methoxy-X04...
Aβ and tau pathology in 3xTg-AD mice. (A-C) Immunofluorescence images of hippocampal and cortical slices of 6, 10, 15, and 20 month-old 3xTg-AD mice stained with 6E10 antibody (A), methoxy-X04 which labels fibrillar aggregates like Aβ plaques (arrows) or neurofibrillary tangles (B). AT8 antibody binds to hyperphosphorylated tau (C). Scale bars: 20...
Dendritic dystrophy in 3xTg-AD mice. In 13 months old 3xTg-AD mice, some dendrites started to become dystrophic while neighboring dendrites showed a normal volume over the whole imaging period of 60 days. Scale bar: 10 µm (AVI)
The pathology of Alzheimer's disease (AD) is characterized by the accumulation of amyloid-β (Aβ) peptide, hyperphosphorylated tau protein, neuronal death, and synaptic loss. By means of long-term two-photon in vivo imaging and confocal imaging, we characterized the spatio-temporal pattern of dendritic spine loss for the first time in 3xTg-AD mice....
Microglia, the immune cells of the brain, can have a beneficial effect in Alzheimer's disease by phagocytosing amyloid-beta. Two-photon in vivo imaging of neuron loss in the intact brain of living Alzheimer's disease mice revealed an involvement of microglia in neuron elimination, indicated by locally increased number and migration velocity of micr...
Alzheimer's disease (AD) represents the most common age-related neurodegenerative disorder. It is characterized by the invariant accumulation of the beta-amyloid peptide (Abeta), which mediates synapse loss and cognitive impairment in AD. Current therapeutic approaches concentrate on reducing Abeta levels and amyloid plaque load via modifying or in...
The method of fluorescence redistribution after photobleaching (FRAP) is increasingly receiving interest in biological applications as it is nowadays used not only to determine mobility parameters per se, but to investigate dynamic changes in the concentration or distribution of diffusing molecules. Here, we develop a new simple convolution-based a...
Phosphoinositide 3-kinase gamma (PI3Kgamma) is activated by Gbetagamma release after stimulation of Galpha i -coupled receptors, involving a recruitment of the enzyme to the plasma membrane via interaction of the regulatory subunit p101 or p87 with Gbetagamma. The receptor-mediated release of Gbetagamma was, however, insufficient to elicit a transl...
