TY - JOUR
T1 - A novel recombinant adeno-associated virus vaccine reduces behavioral impairment and β-amyloid plaques in a mouse model of Alzheimer's disease
AU - Zhang, Jianmin
AU - Wu, Xiaobing
AU - Qin, Chuan
AU - Qi, Jin
AU - Ma, Shibin
AU - Zhang, Huiyuan
AU - Kong, Qingli
AU - Chen, Dongqing
AU - Ba, Denian
AU - He, Wei
PY - 2003/12
Y1 - 2003/12
N2 - Memory impairment progressing to dementia is the main clinical symptom of Alzheimer's disease (AD). Deposition of the amyloid-β peptide (Aβ) in brain, particularly its 42-amino acid isoform (Aβ42), has been shown to play a primary and crucial role in the pathogenesis of AD. In this study we have developed a recombinant adeno-associated virus (AAV) vaccine against AD. This vaccine could express CB-Aβ42 (cholera toxin B subunit and Aβ42 fusion protein) in vivo. A single administration of the AAV-CB-Aβ42 vaccine induced a prolonged, strong production of Aβ-specific serum IgG in transgenic mice that overexpressed the London mutant of amyloid precursor protein (APP/V717I), and resulted in improved ability of memory and cognition, decreased Aβ deposition in the brain, and a resultant decrease in plaque-associated astrocytosis. Our results extended the immunological approaches for the treatment and prevention of AD to an oral, intranasal, or intramuscular route that might be better tolerated in human patients than repetitive parental immunizations in the presence of adjuvant. AAV has attracted tremendous interest as a promising vector for gene delivery. Our results raised the possibility that AAV-CB-Aβ42 vector immunization may provide the basis of a novel and promising Alzheimer's disease vaccination program.
AB - Memory impairment progressing to dementia is the main clinical symptom of Alzheimer's disease (AD). Deposition of the amyloid-β peptide (Aβ) in brain, particularly its 42-amino acid isoform (Aβ42), has been shown to play a primary and crucial role in the pathogenesis of AD. In this study we have developed a recombinant adeno-associated virus (AAV) vaccine against AD. This vaccine could express CB-Aβ42 (cholera toxin B subunit and Aβ42 fusion protein) in vivo. A single administration of the AAV-CB-Aβ42 vaccine induced a prolonged, strong production of Aβ-specific serum IgG in transgenic mice that overexpressed the London mutant of amyloid precursor protein (APP/V717I), and resulted in improved ability of memory and cognition, decreased Aβ deposition in the brain, and a resultant decrease in plaque-associated astrocytosis. Our results extended the immunological approaches for the treatment and prevention of AD to an oral, intranasal, or intramuscular route that might be better tolerated in human patients than repetitive parental immunizations in the presence of adjuvant. AAV has attracted tremendous interest as a promising vector for gene delivery. Our results raised the possibility that AAV-CB-Aβ42 vector immunization may provide the basis of a novel and promising Alzheimer's disease vaccination program.
UR - http://www.scopus.com/inward/record.url?scp=10744225891&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=10744225891&partnerID=8YFLogxK
U2 - 10.1016/j.nbd.2003.07.005
DO - 10.1016/j.nbd.2003.07.005
M3 - Article
C2 - 14678754
AN - SCOPUS:10744225891
SN - 0969-9961
VL - 14
SP - 365
EP - 379
JO - Neurobiology of Disease
JF - Neurobiology of Disease
IS - 3
ER -