NDLI: Muscle-Directed Anti-Aβ Single-Chain Antibody Delivery via AAV1 Reduces Cerebral Aβ Load in an Alzheimer’s Disease Mouse Model

Content Provider	Springer Nature Link
Author	Yang, Junling Pattanayak, Abhinandan Song, Min Kou, Jinghong Taguchi, Hiroaki Paul, Sudhir Ponnazhagan, Selvarangan Lalonde, Robert Fukuchi, Ken ichiro
Copyright Year	2012
Abstract	We previously reported that anti-amyloid-beta (Aβ) single-chain antibody (scFv59) brain delivery via recombinant adeno-associated virus (rAAV) was effective in reducing cerebral Aβ load in an Alzheimer’s disease (AD) mouse model without inducing inflammation. Here, we investigated the prophylactic effects and mechanism of a muscle-directed gene therapy modality in an AD mouse model. We injected rAAV serotype 1 encoding scFv59 into the right thigh muscles of 3-month-old mice. Nine months later, high levels of scFv59 expression were confirmed in the thigh muscles by both immunoblotting and immunohistochemistry. As controls, model mice were similarly injected with rAAV1 encoding antihuman immunodeficiency virus Gag antibody (scFvGag). AAV1-mediated scFv59 gene delivery was effective in decreasing Aβ deposits in the brain. Compared with the scFvGag group, levels of Aβ in cerebrospinal fluid (CSF) decreased significantly while Aβ in serum tended to increase in the scFv59 group. AAV1-mediated scFv59 gene delivery may alter the equilibrium of Aβ between the blood and brain, resulting in an increased efflux of Aβ from the brain owing to antibody-mediated sequestration/clearance of peripheral Aβ. Our results suggest that muscle-directed scFv59 delivery via rAAV1 may be a prophylactic option for AD and that levels of CSF Aβ may be used to evaluate the efficacy of anti-Aβ immunotherapy.
Starting Page	277
Ending Page	288
Page Count	12
File Format	PDF
ISSN	08958696
Journal	Journal of Molecular Neuroscience
Volume Number	49
Issue Number	2
e-ISSN	15591166
Language	English
Publisher	Humana Press Inc
Publisher Date	2012-09-04
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Single-chain antibody Adeno-associated virus Amyloid Alzheimer’s disease Cerebrospinal fluid Neurosciences Neurochemistry Cell Biology Proteomics Neurology
Content Type	Text
Resource Type	Article
Subject	Medicine Cellular and Molecular Neuroscience

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