TY - JOUR
T1 - Filamentous phage as vector-mediated antibody delivery to the brain
AU - Frenkel, Dan
AU - Solomon, Beka
PY - 2002/4/16
Y1 - 2002/4/16
N2 - Early diagnosis of Alzheimer's disease is prevented by lack of means to visualize and target β 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-β 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-β amyloid antibody fragment into Alzheimer's APP transgenic mice enables in vivo targeting of β amyloid plaques. The plaques were covisualized both by thioflavin-S and fluorescent-labeled antiphage 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 Aβ deposits in vivo would arguably provide the most useful diagnostic and monitoring test for early diagnosis of Alzheimer's disease.
AB - Early diagnosis of Alzheimer's disease is prevented by lack of means to visualize and target β 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-β 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-β amyloid antibody fragment into Alzheimer's APP transgenic mice enables in vivo targeting of β amyloid plaques. The plaques were covisualized both by thioflavin-S and fluorescent-labeled antiphage 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 Aβ deposits in vivo would arguably provide the most useful diagnostic and monitoring test for early diagnosis of Alzheimer's disease.
UR - http://www.scopus.com/inward/record.url?scp=0037117459&partnerID=8YFLogxK
U2 - 10.1073/pnas.072027199
DO - 10.1073/pnas.072027199
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AN - SCOPUS:0037117459
SN - 0027-8424
VL - 99
SP - 5675
EP - 5679
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 8
ER -