Lentiviral Vector-Based Models of Amyloid Pathology: From Cells to Animals

Authors: Shaughnessy, Laura; Thomas, Mary B.; Wakefield, John; Chamblin, Beth; Nair, Ayyappan; Koentgen, Frank; Ramabhadran, Ram

Source: Current Alzheimer Research, Volume 2, Number 2, April 2005 , pp. 239-247(9)

Publisher: Bentham Science Publishers

Buy & download fulltext article:

Price: $63.10 plus tax (Refund Policy)

Abstract:

Lentiviral vectors are efficient tools for the introduction of genes into a wide range of established and primary cells in vitro, ex vivo, and in vivo, and also permit efficient transgenesis in a wide range of mammalian species. Our goals have been to apply the broad capabilities of the lentiviral vector system to AD research. Using a set of vectors expressing APP and PS1 genes, we demonstrated the efficiency and fidelity of the system for in vitro biochemical analyses of genes and pathways involved in plaque deposition. These analyses were performed in cell lines and in primary neuronal cultures, which have previously been difficult to use. The methods and tools described here are applicable to the study of effects of other genes and gene combinations on APP processing, including suppression of gene activity by delivering shRNAs. We have attempted to create local plaque pathology by stereotactic injection of APP and PS1 expressing vectors into mouse brains for use as a rapid model for plaque pathology that can be used in a broad range of mammals. No amyloid or preamyloid pathology has been detected over a six-month period; the possible reasons are discussed. Lastly, we have used the vectors to create transgenic rats expressing mutant APP and mutant PS1 and have obtained the first set of positive pups with more expected. The results presented here demonstrate the utility of Lentiviral vector-based approaches to the study of AD and other neurodegenerative diseases.

Keywords: app; presenilin; transgenic rat; primary neuronal cultures

Document Type: Review article

DOI: http://dx.doi.org/10.2174/1567205053585963

Affiliations: 1: Tranzyme Pharma Inc., 21 Davis Drive, Research Triangle Park, NC 27709, USA.

Publication date: 2005-04-01

More about this publication?

Current Alzheimer Research publishes peer-reviewed frontier review and research articles on all areas of Alzheimer's disease. This multidisciplinary journal will help in understanding the neurobiology, genetics, pathogenesis, and treatment strategies of Alzheimer's disease. The journal publishes objective reviews written by experts and leaders actively engaged in research using cellular, molecular, and animal models. The journal also covers original articles on recent research in fast emerging areas of molecular diagnostics, brain imaging, drug development and discovery, and clinical aspects of Alzheimer's disease. Manuscripts are encouraged that relate to the synergistic mechanism of Alzheimer's disease with other dementia and neurodegenerative disorders. Book reviews, meeting reports and letters-to-the-editor are also published. The journal is essential reading for researchers, educators and physicians with interest in age-related dementia and Alzheimer's disease. Current Alzheimer Research provides a comprehensive 'bird's-eye view' of the current state of Alzheimer's research for neuroscientists, clinicians, health science planners, granting, caregivers and families of this devastating disease.

Lentiviral Vector-Based Models of Amyloid Pathology: From Cells to Animals

Buy & download fulltext article:

Tools

Key

Text size:

Useful pages