A novel recombinant adeno-associated virus vaccine reduces behavioral impairment and b-amyloid plaques in a mouse model of Alzheimer's disease

• Published in: Neurobiology of disease 2003-12, Vol.14 (3), p.365-379
• Main Authors: Zhang, Jianmin, Wu, Xiaobing, Qin, Chuan, Qi, Jin, Ma, Shibin, Zhang, Huiyuan, Kong, Qingli, Chen, Dongqing, Ba, Denian, He, Wei
• Format: Article
• Language: English
• Subjects: Adeno-associated virus
• ISSN: 0969-9961
• DOI: 10.1016/j.nbd.2003.07.005

Memory impairment progressing to dementia is the main clinical symptom of Alzheimer's disease (AD). Deposition of the amyloid-b peptide (Ab) in brain, particularly its 42-amino acid isoform (Ab42), 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-Ab42 (cholera toxin B subunit and Ab42 fusion protein) in vivo. A single administration of the AAV-CB-Ab42 vaccine induced a prolonged, strong production of Ab-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 Ab 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-Ab42 vector immunization may provide the basis of a novel and promising Alzheimer's disease vaccination program.