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Dive into the research topics where Ursula Lübke is active.

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Featured researches published by Ursula Lübke.


Acta Neuropathologica | 1992

Monoclonal antibodies with selective specificity for Alzheimer Tau are directed against phosphatase-sensitive epitopes.

Marc Mercken; Marc Vandermeeren; Ursula Lübke; Jan Six; Jef Boons; André Van de Voorde; Jean-Jacques Martin; J. Gheuens

SummaryA modified form of the microtubule-associated protein Tau is the major component of the paired helical filaments (PHF) found in Alzheimers disease. The characterization of these posttranslational Tau modifications is hindered by the lack of sufficient PHF-Tau-specific markers. Here we describe several monoclonal antibodies, prepared by immunization with PHF, two of which showed a selective specificity for PHF-Tau without cross-reactivity with normal Tau. Epitope recognition by these two monoclonals was sensitive to alkaline phosphatase treatment. In Western blotting these monoclonal antibodies reacted specifically with the abnormally phosphorylated epitopes on Alzheimers disease-associated PHF-Tau. One of the new antibodies can be used for the construction of a sandwich enzyme-linked immunosorbent assay for the specific detection of PHF-Tau without cross-reactivity to normal Tau proteins.


Neurobiology of Disease | 2000

Behavioral Disturbances without Amyloid Deposits in Mice Overexpressing Human Amyloid Precursor Protein with Flemish (A692G) or Dutch (E693Q) Mutation

Samir Kumar-Singh; Ilse Dewachter; Dieder Moechars; Ursula Lübke; Chris De Jonghe; Chantal Ceuterick; Frédéric Checler; Asha Naidu; Barbara Cordell; Patrick Cras; Christine Van Broeckhoven; Fred Van Leuven

The contribution of mutations in the amyloid precursor protein (APP) gene known as Flemish (APP/A692G) and Dutch (APP/E693Q) to the pathogenesis of Alzheimers disease and hereditary cerebral hemorrhage with amyloidosis of the Dutch type, respectively, was studied in transgenic mice that overexpress the mutant APP in brain. These transgenic mice showed the same early behavioral disturbances and defects and increased premature death as the APP/London (APP V717I), APP/Swedish (K670N, M671L), and other APP transgenic mice described previously. Pathological changes included intense glial reaction, extensive microspongiosis in the white matter, and apoptotic neurons in select areas of the brain, while amyloid deposits were absent, even in mice over 18 months of age. This contrasts with extensive amyloid deposition in APP/London transgenic mice and less pronounced amyloid deposition in APP/Swedish transgenic mice generated identically. It demonstrated, however, that the behavioral deficiencies and the pathological changes in brain resulting from an impaired neuronal function are caused directly by APP or its proteolytic derivative(s). These accelerate or impinge on the normal process of aging and amyloid deposits per se are not essential for this phenotype.


American Journal of Pathology | 2002

Dense-Core Senile Plaques in the Flemish Variant of Alzheimer's Disease Are Vasocentric

Samir Kumar-Singh; Patrick Cras; Rong Wang; John M. Kros; Johan van Swieten; Ursula Lübke; Chantal Ceuterick; Sally Serneels; Krist’l Vennekens; Jean-Pierre Timmermans; Eric Van Marck; Jean-Jacques Martin; Cornelia M. van Duijn; Christine Van Broeckhoven

Alzheimers disease (AD) is characterized by deposition of beta-amyloid (Abeta) in diffuse and senile plaques, and variably in vessels. Mutations in the Abeta-encoding region of the amyloid precursor protein (APP) gene are frequently associated with very severe forms of vascular Abeta deposition, sometimes also accompanied by AD pathology. We earlier described a Flemish APP (A692G) mutation causing a form of early-onset AD with a prominent cerebral amyloid angiopathy and unusually large senile plaque cores. The pathogenic basis of Flemish AD is unknown. By image and mass spectrometric Abeta analyses, we demonstrated that in contrast to other familial AD cases with predominant brain Abeta42, Flemish AD patients predominantly deposit Abeta40. On serial histological section analysis we further showed that the neuritic senile plaques in APP692 brains were centered on vessels. Of a total of 2400 senile plaque cores studied from various brain regions from three patients, 68% enclosed a vessel, whereas the remainder were associated with vascular walls. These observations were confirmed by electron microscopy coupled with examination of serial semi-thin plastic sections, as well as three-dimensional observations by confocal microscopy. Diffuse plaques did not associate with vessels, or with neuritic or inflammatory pathology. Together with earlier in vitro data on APP692, our analyses suggest that the altered biological properties of the Flemish APP and Abeta facilitate progressive Abeta deposition in vascular walls that in addition to causing strokes, initiates formation of dense-core senile plaques in the Flemish variant of AD.


Neurology | 1991

Early‐onset Alzheimer's disease in 2 large Belgian families

J. J. Martin; J. Gheuens; Marc Bruyland; Patrick Cras; Antoon Vandenberghe; Colin L. Masters; Konrad Beyreuther; R. Dom; Chantal Ceuterick; Ursula Lübke; H. Van Heuverswijn; G. De Winter; C. Van Broeckhoven

Familial Alzheimers disease (FAD) is a dominantly inherited condition that may present with an early onset, and myoclonus occurs frequently in the course of the disease. We report clinical and neuropathologic data on 2 large Belgian families with FAD in which we obtained 17 autopsies of the CNS. In family A, each of 11 autopsies had the typical neuropathologic features of Alzheimers disease (AD), and there were a few cerebellar plaques in the molecular layer. In family B, in addition to the typical characteristics of AD in 6 autopsies, there were numerous amyloid plaques in the cortical cerebellar layers. In both families, we immunostained the amyloid deposits for the A4 protein, and they were negative for prion-associated protein immunoreactivity.


Neurobiology of Aging | 2002

The role of cytokines, astrocytes, microglia and apoptosis in Creutzfeldt-Jakob disease

B. Van Everbroeck; E Dewulf; Ph. Pals; Ursula Lübke; J. J. Martin; Patrick Cras

In order to investigate inflammation and apoptosis in Creutzfeldt-Jakob disease (CJD) patients, we analyzed astrocytes, microglia and apoptotic neurons in brain and IL-1beta in cerebrospinal fluid (CSF). Our results showed increased numbers of astrocytes in CJD and increased numbers of microglia and apoptotic neurons both in CJD and Alzheimers disease (AD) as compared to controls. All these markers correlated (P < 0.001) with the severity of the neuropathological lesions. An increased IL-1beta concentration was found in AD and CJD CSF that correlated with the number of microglia and which did not change in the disease course of CJD.In conclusion, apoptotic neurons in CJD correlates to the neuropathological lesions and are probably related to the presence of inflammatory cells and cytokines which are present during the whole CJD disease process.


Acta Neuropathologica | 2004

Extracellular protein deposition correlates with glial activation and oxidative stress in Creutzfeldt-Jakob and Alzheimer’s disease

Bart Van Everbroeck; Itte Dobbeleir; Michèle De Waele; Evelyn De Leenheir; Ursula Lübke; Jean-Jacques Martin; Patrick Cras

The relation of protein deposition with glial cells and oxidative stress was studied in Creutzfeldt-Jakob disease (CJD), Alzheimer’s disease (AD) and neurologically healthy control patients. Three neocortical areas, the hippocampus, and the cerebellum of 20 CJD, 10 AD and 10 control patients were immunohistochemically examined for the presence of astroglia, microglia, and protein depositions. To investigate the level of oxidative stress the percentage of neurons with cytoplasmic hydroxylated DNA was determined. Astroglia, microglia and oxidative stress were located around amyloid-β depositions and a clear quantitative relation was identified. These markers were only increased in the hippocampus of AD compared to controls. Quantitative analysis in these groups showed a correlation between the oxidative stress level and the number of microglia in the grey matter. All markers were increased in the grey matter and the cerebellum of CJD when compared to AD and controls. The highest numbers of lesions were observed in a CJD population with a rapid disease progression. Quantitative analysis showed a correlation between the oxidative stress level and all glial cells. Further analysis showed that the number of microglia was related to the intensity of the prion depositions. Glial cells in the brain are thought to be the main producers of oxidative stress, resulting in neuronal death. Our results confirm that this close relationship exists in both AD and CJD. We also show that an increased number of glial cells and therefore possibly oxidative stress is associated with the disease progression.


Journal of Neuropathology and Experimental Neurology | 2006

Characterization of Ubiquitinated Intraneuronal Inclusions in a Novel Belgian Frontotemporal Lobar Degeneration Family

Daniel Pirici; Rik Vandenberghe; Rosa Rademakers; Bart Dermaut; Marc Cruts; Krist'l Vennekens; Ivy Cuijt; Ursula Lübke; Chantal Ceuterick; Jean Jacques Martin; Christine Van Broeckhoven; Samir Kumar-Singh

The most common histologic feature in patients with frontotemporal lobar degeneration (FTLD) is intracellular brain inclusions of yet uncharacterized proteins that react with antiubiquitin (Ub) antibodies, but not with tau or synuclein (FTLD-U). We identified a four-generation Belgian FTLD family in which 8 patients had dominantly inherited FTLD. In one patient, we showed frontotemporal atrophy with filamentous Ub-positive intracellular inclusions in absence of tau pathology or any alterations in the levels of soluble tau. We characterized the cellular and subcellular localization and morphology of the inclusions. Ub-positive inclusions predominantly occurred within neurons (>97%), but were also observed within oligodendroglia (approximately 2%) and microglia (<1%), but not within astroglia. Regarding the subcellular localization, the intranuclear inclusions (INI) were up to approximately four-fold more frequent than the cytoplasmic inclusions, although the latter were more specific to neurons. The INIs frequently appeared spindle-shaped and 3-dimensional confocal reconstructions identified flattened, leaf-like structures. Ultrastructurally, straight 10- to 18-nm-diameter filaments constituted the spindle-shaped inclusions that occurred in close proximity to the nuclear membrane. Staining for HSP40, p62, and valosin/p97 was observed in only a minority of the inclusions. Whereas the precise nature of the protein remains elusive, characterization of such familial FTLD-U patients would be helpful in identifying a common denominator in the pathogenesis of familial and the more prevalent sporadic FTLD-U.


Molecular Brain Research | 1999

Identification and localization of ataxin-7 in brain and retina of a patient with cerebellar ataxia type II using anti-peptide antibody

Claire Mauger; Jurgen Del-Favero; Chantal Ceuterick; Ursula Lübke; Christine Van Broeckhoven; Jean-Jacques Martin

Autosomal dominant cerebellar ataxias (ADCAs) are a complex group of neurodegenerative disorders characterized by progressive degeneration of the cerebellum, brain stem and spinal cord. The spinocerebellar ataxia type 7 (SCA7) is associated with pigmentary macular dystrophy and retinal degeneration leading to blindness caused by a CAG/polyglutamine (polyGln) expansion in the coding region of the SCA7 gene/protein. The SCA7 gene codes for ataxin-7, a protein of unknown function. To investigate its cellular and subcellular localization, we have developed a sequence-specific polyclonal antibody against the N-terminal part of the protein. Immunohistochemical analysis indicated that ataxin-7 accumulates as single nuclear inclusion (NI) in the cells of the brain and retina of a SCA7 patient but not of controls. The 1C2 antibody, directed against expanded polyGln, confirmed the aggregation of mutant ataxin-7 in these NIs. Furthermore, ubiquitin was found in these aggregates, suggesting that mutant ataxin-7 is a target for ubiquitin-dependent proteolysis, but resistant to removal. Electron microscopic studies using immunogold labeling showed that ataxin-7 immunoreactive NIs appear as dense aggregates containing a mixture of granular and filamentary structures. Together, these data confirm the presence of NIs in brain and retina of a SCA7 patient, a common characteristic of disorders caused by expanded CAG/polyGln repeats.


Journal of Neurochemistry | 1992

Affinity Purification of Human τ Proteins and the Construction of a Sensitive Sandwich Enzyme‐Linked Immunosorbent Assay for Human τ Detection

Marc Mercken; Mark Vandermeeren; Ursula Lübke; Jan Six; Jef Boons; Eugène Vanmechelen; Andre Van De Voorde; J. Gheuens

Abstract: Immunoaffinity chromatography with a monoclonal antibody produced against bovine τ protein was used to purify τ proteins from human brain. Fifty grams of brain tissue yielded τ 2 mg of pure τ proteins. The affinity‐purified human τ was used to produce a high‐titered rabbit anti‐human τ serum. The monoclonal anti‐τ antibody and the polyclonal rabbit anti‐τ serum were then used to construct a sandwich enzyme‐linked immunosorbent assay for detection of human τ proteins, with a sensitivity of 1 ng/ml.


Brain Research | 1993

Rimmed vacuoles of inclusion body myositis and oculopharyngeal muscular dystrophy contain amyloid precursor protein and lysosomal markers

Marcello Villanova; Mitsuru Kawai; Ursula Lübke; Shin J. Oh; George Perry; Jan Six; Chantal Ceuterick; Jean Jacques Martin; Patrick Cras

Rimmed vacuoles are small areas of focal destruction of muscle fibres, found in inclusion body myositis, oculopharyngeal muscular dystrophy and other muscle disorders. They are known to contain amyloid proteins, probably of beta-amyloid type. We examined rimmed vacuoles immunohistochemically in 12 patients with inclusion body myositis and two patients with oculopharyngeal muscular dystrophy with antibodies to beta-amyloid precursor protein and cathepsin B and D. We found evidence for the presence of all these markers in rimmed vacuoles. These results confirm the presence of beta-amyloid in rimmed vacuoles, and provide additional support for the hypotheses that rimmed vacuoles are of lysosomal origin and that lysosomes are probably important in the metabolism of amyloid precursor protein.

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Patrick Cras

Case Western Reserve University

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Jef Boons

University of Antwerp

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