Transgenic potato expressing Aβ reduce Aβ burden in Alzheimer's disease mouse model

Beta amyloid (Aβ) is believed one of the major pathogens of Alzheimer's disease (AD), and the reduction of Aβ is considered a primary therapeutic target. Immunization with Aβ can reduce Aβ burden and pathological features in transgenic AD model mice. Transgenic potato plants were made using genes encoding 5 tandem repeats of Aβ1–42 peptides with an ER retention signal. Amyloid precursor protein transgenic mice (Tg2576) fed with transgenic potato tubers with adjuvant showed a primary immune response and a partial reduction of Aβ burden in the brain. Thus, Aβ tandem repeats can be expressed in transgenic potato plants to form immunologically functional Aβ, and these potatoes has a potential to be used for the prevention and treatment of AD.

[1]  J. Clements,et al.  Edible vaccine protects mice against Escherichia coli heat-labile enterotoxin (LT): potatoes expressing a synthetic LT-B gene. , 1998, Vaccine.

[2]  R. Motter,et al.  Immunization with amyloid-β attenuates Alzheimer-disease-like pathology in the PDAPP mouse , 1999, Nature.

[3]  H. Mason,et al.  Oral immunization with a recombinant bacterial antigen produced in transgenic plants , 1995, Science.

[4]  I. Mook‐Jung,et al.  Neuroprotective effects of estrogen against beta-amyloid toxicity are mediated by estrogen receptors in cultured neuronal cells , 2001, Neuroscience Letters.

[5]  Seung-Bum Lee,et al.  Expression of the native cholera toxin B subunit gene and assembly as functional oligomers in transgenic tobacco chloroplasts , 2001, Journal of Molecular Biology.

[6]  R. Bhatnagar,et al.  Expression of protective antigen in transgenic plants: a step towards edible vaccine against anthrax. , 2002, Biochemical and biophysical research communications.

[7]  J. R. Liu,et al.  Cadmium resistance in transgenic tobacco plants expressing the Nicotiana glutinosa L. metallothionein-like gene. , 1998, Molecules and cells.

[8]  Wei He,et al.  A novel recombinant adeno-associated virus vaccine reduces behavioral impairment and β-amyloid plaques in a mouse model of Alzheimer's disease , 2003, Neurobiology of Disease.

[9]  M. Citron,et al.  Strategies for disease modification in Alzheimer's disease , 2004, Nature Reviews Neuroscience.

[10]  J. Hardy,et al.  Aβ peptide vaccination prevents memory loss in an animal model of Alzheimer's disease , 2000, Nature.

[11]  R. Rose,et al.  Oral Immunogenicity of Human Papillomavirus-Like Particles Expressed in Potato , 2003, Journal of Virology.

[12]  B. Dubois,et al.  Subacute meningoencephalitis in a subset of patients with AD after Aβ42 immunization , 2003, Neurology.

[13]  H. S. Kim,et al.  Expression of the hepatitis B surface S and preS2 antigens in tubers of Solanum tuberosum , 2004, Plant Cell Reports.

[14]  D. Butterfield.  Amyloid beta-peptide (1-42)-induced oxidative stress and neurotoxicity: implications for neurodegeneration in Alzheimer's disease brain. A review. , 2002, Free radical research.

[15]  Ralph A. Nixon,et al.  Aβ peptide immunization reduces behavioural impairment and plaques in a model of Alzheimer's disease , 2000, Nature.

[16]  H. Weiner,et al.  Oral tolerance: mechanisms and therapeutic applications. , 1999, Advances in immunology.

[17]  R. Doody.  Therapeutic standards in Alzheimer disease. , 1999, Alzheimer disease and associated disorders.

[18]  J. Hardy,et al.  The Amyloid Hypothesis of Alzheimer ’ s Disease : Progress and Problems on the Road to Therapeutics , 2009 .

[19]  B Frangione,et al.  Immunization with a nontoxic/nonfibrillar amyloid-beta homologous peptide reduces Alzheimer's disease-associated pathology in transgenic mice. , 2001, The American journal of pathology.

[20]  D. Holtzman,et al.  Evidence for peripheral clearance of cerebral Aβ protein following chronic, active Aβ immunization in PSAPP mice , 2003, Neurobiology of Disease.

[21]  I. Mook‐Jung,et al.  Expression of human β-amyloid peptide in transgenic potato , 2003 .

[22]  Kate A. Stafford,et al.  Efficient reversal of Alzheimer's disease fibril formation and elimination of neurotoxicity by a small molecule. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[23]  W. Richards,et al.  Mice deficient in BACE1, the Alzheimer's β-secretase, have normal phenotype and abolished β-amyloid generation , 2001, Nature Neuroscience.

[24]  M. L. Alvarez,et al.  Expression of the B subunit of Escherichia coli heat-labile enterotoxin as a fusion protein in transgenic tomato , 2003, Plant Cell Reports.

[25]  David J. Cummins,et al.  Peripheral anti-Aβ antibody alters CNS and plasma Aβ clearance and decreases brain Aβ burden in a mouse model of Alzheimer's disease , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[26]  Jay S. Fine,et al.  Chronic Treatment with the γ-Secretase Inhibitor LY-411,575 Inhibits β-Amyloid Peptide Production and Alters Lymphopoiesis and Intestinal Cell Differentiation* , 2004, Journal of Biological Chemistry.

[27]  D. M. Lam,et al.  Expression of hepatitis B surface antigen in transgenic plants. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[28]  M. Estes,et al.  Expression of Norwalk virus capsid protein in transgenic tobacco and potato and its oral immunogenicity in mice. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[29]  D. Price,et al.  Mutant genes in familial Alzheimer's disease and transgenic models. , 1998, Annual review of neuroscience.

[30]  J. Hardy,et al.  Aβ42 Is Essential for Parenchymal and Vascular Amyloid Deposition in Mice , 2005, Neuron.

[31]  Gregory A. Hickey,et al.  Amyloid-β Antibody Treatment Leads to Rapid Normalization of Plaque-Induced Neuritic Alterations , 2003, The Journal of Neuroscience.

[32]  D. Selkoe,et al.  Immune hyporesponsiveness to amyloid β-peptide in amyloid precursor protein transgenic mice: Implications for the pathogenesis and treatment of Alzheimer's disease , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[33]  K. Fischbeck,et al.  Toxic Proteins in Neurodegenerative Disease , 2002, Science.

[34]  W. Langridge,et al.  Expression of cholera toxin B subunit oligomers in transgenic potato plants , 1997, Transgenic Research.

[35]  D. Westaway,et al.  Therapeutically effective antibodies against amyloid-β peptide target amyloid-β residues 4–10 and inhibit cytotoxicity and fibrillogenesis , 2002, Nature Medicine.

[36]  R. Motter,et al.  Epitope and isotype specificities of antibodies to β-amyloid peptide for protection against Alzheimer's disease-like neuropathology , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[37]  M. Levine,et al.  Immunogenicity in humans of a recombinant bacterial antigen delivered in a transgenic potato , 1998, Nature Medicine.

[38]  M. Hagan,et al.  Methanesulfonyl fluoride (MSF): a double-blind, placebo-controlled study of safety and efficacy in the treatment of senile dementia of the Alzheimer type. , 1999, Alzheimer disease and associated disorders.

[39]  D. Wilcock,et al.  Microglial activation facilitates Aβ plaque removal following intracranial anti-Aβ antibody administration , 2004, Neurobiology of Disease.

[40]  J. Carrington,et al.  Nuclear transport of plant potyviral proteins. , 1990, The Plant cell.

[41]  M. Citron,et al.  Anti-Inflammatory Drug Therapy Alters β-Amyloid Processing and Deposition in an Animal Model of Alzheimer's Disease , 2003, The Journal of Neuroscience.

[42]  C. Arntzen,et al.  Production of hepatitis B surface antigen in transgenic plants for oral immunization , 2000, Nature Biotechnology.

[43]  C. Arntzen,et al.  Oral immunization with hepatitis B surface antigen expressed in transgenic plants , 2001, Proceedings of the National Academy of Sciences of the United States of America.