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365 results on '"Games, D."'

8. Amyloid precursor protein processing and Abeta42 deposition in a transgenic mouse model of Alzheimer disease

Author

Johnson-Wood, K., Lee, M., Motter, R., Hu, K., Gordon, g., Barbour, R., Khan, K., Gordon, M., Tan, H., Games, D., Lieberburg, I., Schenk, d., Seubert, P., and McConlogue, L.

Subjects
Protein metabolism -- Research, Genetically modified mice -- Physiological aspects, Alzheimer's disease -- Models, Science and technology
Abstract

The PDAPP transgenic mouse, which over-expresses human amyloid precursor protein (APP717V [right arrow] F), has been shown to develop much of the pathology associated with Alzheimer disease. In this report, levels of APP and its amyloidogenic metabolites were measured in brain regions of transgenic mice between 4 and 18 months of age. While absolute levels of APP expression likely contribute to the rate of amyloid [Beta]-peptide (A[Beta]) deposition, regionally specific factors also seem important, as homozygotic mice express APP levels in pathologically unaffected regions in excess of that measured in certain amyloid plaque-prone regions of heterozygotic mice. Regional levels of APP and APP-[Beta] were nearly constant at all ages, while A[Beta] levels dramatically and predictably increased in brain regions undergoing histochemically confirmed amyloidosis, most notably in the cortex and hippocampus. In hippocampus, A[Beta] concentrations increase 17-fold between the ages of 4 and 8 months, and by 18 months of age are over 500-fold that at 4 months, reaching an average level in excess of 20 nmol of A[Beta] per g of tissue. A[[Beta].sub.1-42] constitutes the vast majority of the depositing A[Beta] species. The similarities observed between the PDAPP mouse and human Alzheimer disease with regard to A[[Beta].sub.42] deposition occurring in a temporally and regionally specific fashion further validate the use of the model in understanding processes related to the disease.

Published
1997

16. Abeta species removal after abeta42 immunization

Author

Nicoll JA, Barton E, Boche D, Neal JW, Ferrer I, Thompson P, Wilkinson D, Bayer A, Games D, Seubert P, Schenk D, Holmes C., VLACHOULI, CHRISTINA, Nicoll, Ja, Barton, E, Boche, D, Neal, Jw, Ferrer, I, Thompson, P, Vlachouli, Christina, Wilkinson, D, Bayer, A, Games, D, Seubert, P, Schenk, D, and Holmes, C.

Subjects
Microscopy, Confocal, Amyloid beta-Peptides, Alzheimer Vaccines, Alzheimer's disease, diagnosis/metabolism/physiopathology, Amyloid beta-Peptides, Molecular Sequence Data, Brain, Neurofibrillary Tangles, Neuropil Threads, Immunohistochemistry, Peptide Fragments, Cerebral Amyloid Angiopathy, Phagocytosis, Alzheimer Disease, diagnosis/metabolism/physiopathology, Image Processing, Computer-Assisted, Humans, Amino Acid Sequence, Microglia, Randomized Controlled Trials as Topic
Abstract

Neuropathologic examination of 3 patients with Alzheimer disease in the Elan Pharmaceuticals trial using antibodies specific for different Abeta species showed in one case, 4 months after the immunization, evidence of a stage of active plaque clearance with "moth-eaten" plaques and abundant Abeta phagocytosis by microglia. At 1 to 2 years after immunization, 2 cases showed extensive areas cleared of plaques (69% and 86% of the temporal cortex was plaque-free). Cortex cleared of plaques in all 3 cases had a characteristic constellation of features, including a very low plaque burden, sparse residual dense plaque cores, and phagocytosed Abeta within microglia. There was resolution of tau-containing dystrophic neurites, although other features of tau pathology (tangles and neuropil threads) remained and cerebral amyloid angiopathy persisted. Although most antibodies generated by Abeta42 immunization in humans bind the intact N-terminus, immunohistochemistry with specific antibodies showed clearance of all major species of Abeta (Abeta40, Abeta42, and N-terminus truncated Abeta). Abeta immunotherapy can clear all Abeta species from the cortex. However, if it is to be used for treatment of established Alzheimer disease, then the residual tau pathology and cerebral amyloid angiopathy require further study.

Published
2006

28. Reducing C-Terminal-Truncated Alpha-Synuclein by Immunotherapy Attenuates Neurodegeneration and Propagation in Parkinson's Disease-Like Models

Author

Games, D., primary, Valera, E., additional, Spencer, B., additional, Rockenstein, E., additional, Mante, M., additional, Adame, A., additional, Patrick, C., additional, Ubhi, K., additional, Nuber, S., additional, Sacayon, P., additional, Zago, W., additional, Seubert, P., additional, Barbour, R., additional, Schenk, D., additional, and Masliah, E., additional

Published
2014
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32. Immunotherapy Reduces Vascular Amyloid- in PDAPP Mice

Author

Schroeter, S., primary, Khan, K., additional, Barbour, R., additional, Doan, M., additional, Chen, M., additional, Guido, T., additional, Gill, D., additional, Basi, G., additional, Schenk, D., additional, Seubert, P., additional, and Games, D., additional

Published
2008
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33. Antibodies to non-beta regions of the beta-amyloid precursor protein detect a subset of senile plaques

Author

Joachim, C., Games, D., Morris, J., Ward, P., Frenkel, D., and Selkoe, D.

Subjects
Neurons, Amyloid beta-Protein Precursor, Amyloid beta-Peptides, Staining and Labeling, Alzheimer Disease, mental disorders, Immunologic Techniques, Brain, Humans, Protein Precursors, Antibodies, Axons, Research Article
Abstract

A central unresolved issue in Alzheimer's disease is the origin of the extracellular amyloid beta protein (A beta P) found in senile plaques and its relationship to the dystrophic neurites that intimately surround it. Here the presence and distribution within senile plaques of various epitopes of the beta-amyloid precursor protein (APP) are compared with the distribution of A beta P itself and markers for plaque neurites. Several principal findings emerge: 1) antibodies to regions of APP outside of A beta P ('APP antibodies') recognize only a subgroup of senile plaques; 2) within these plaques, APP antibodies label discrete globular and granular structures morphologically resembling neurites; 3) virtually all of the plaques labeled by APP antibodies also contain neurites reactive with antibodies to tau; 4) double labeling with anti-tau and an APP antibody shows that the neuritelike profiles stained by the APP antibody are always closely associated with tau-positive neurites within the same plaque and that a minority of profiles appear to be labeled by both antibodies; and 5) antibodies to different regions throughout APP label the same profiles within plaques, suggesting the presence of the full-length precursor. The authors conclude that only a subgroup of senile plaques contain APP epitopes and that the immunostained structures are neurites. Because many A beta P-containing plaques in neocortex, cerebellum, and striatum were found to be devoid of any APP labeling, as were vascular A beta P deposits, it is unlikely that the extracellular A beta P is principally derived from the APP found within dystrophic neurites. The immunodetection of apparently full-length APP, an axonally transported protein, in selected plaque neurites provides yet another protein marker of neuritic dystrophy, possibly indicative of an aberrant regenerative response.

Published
1991

38. Urinary Modified Nucleosides as Tumor Markers

Author

Dudley, E., primary, Lemiere, F., additional, Van Dongen, W., additional, Esmans, E., additional, El‐Sharkawi, A. M. M., additional, Games, D. E., additional, Brenton, A. G., additional, and Newton, R. P., additional

Published
2004
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39. Urinary Modified Nucleosides as Tumor Markers

Author

Dudley, E., primary, Lemiere, F., additional, Van Dongen, W., additional, Esmans, E., additional, El-Sharkawi, A. M. M., additional, Games, D. E., additional, Newton, R. P., additional, and Brenton, A. G., additional

Published
2003
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40. INDUSTRIAL SCALE-UP OF COUNTERCURRENT CHROMATOGRAPHY

Author

Sutherland, I. A., primary, Booth, A. J., additional, Brown, L., additional, Kemp, B., additional, Kidwell, H., additional, Games, D., additional, Graham, A. S., additional, Guillon, G. G., additional, Hawes, D., additional, Hayes, M., additional, Janaway, L., additional, Lye, G. J., additional, Massey, P., additional, Preston, C., additional, Shering, P., additional, Shoulder, T., additional, Strawson, C., additional, and Wood, P., additional

Published
2001
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44. The mode of action of neuropeptides and its relevance for brain diseases

Author

Hökfelt, T., primary, Xu, Z.-Q., additional, Sergeyev, V., additional, Diez, M., additional, Broberger, C., additional, Holmberg, K., additional, Ubink, R., additional, Schött, P., additional, Ögren, S.-O., additional, Kahl, U., additional, Bartfai, T., additional, Lendahl, U., additional, Hurd, Y., additional, Petersson, S., additional, Lavebratt, K., additional, Johansen, J., additional, Schalling, M., additional, Koistinaho, J., additional, Kahn, K., additional, Games, D., additional, DeArmond, S.J., additional, and Prusiner, S., additional

Published
2000
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