Filamentous phage as vector-mediated antibody delivery to the brain.
Early diagnosis of Alzheimer's disease is prevented by lack of means to visualize and target beta amyloid plaques in the brains of affected people. There are many methods of detecting amyloid plaques by staining postmortem brain tissue, but none are available for monitoring in living patients. We propose anti-beta amyloid antibodies as a highly specific probe to monitor amyloid plaque formation in living patients. Intranasal administration of filamentous phage as delivery vector of anti-beta amyloid antibody fragment into Alzheimer's APP transgenic mice enables in vivo targeting of beta amyloid plaques. The plaques were co-visualized both by thioflavin-S and fluorescent-labeled anti-phage antibodies in the olfactory bulb and the hippocampus region. The genetically engineered filamentous bacteriophage proved to be an efficient and nontoxic viral delivery vector to the brain, offering an obvious advantage over other mammalian vectors. The ability to image A beta deposits in vivo would arguably provide the most useful diagnostic and monitoring test for early diagnosis of Alzheimer's disease.
Frenkel
Dan
D
Department of Molecular Microbiology and Biotechnology, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Ramat Aviv, Tel Aviv 69978, Israel.
Solomon
Beka
B
D000544:Alzheimer Disease / Q000175:diagnosis* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000276:immunology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D005822:Genetic Vectors; D007128:Immunoglobulin Fragments / Q000378:metabolism; D017912:Inovirus / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D009154:Mutation
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D007128:Immunoglobulin Fragments