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

Jianmin Zhang, Xiaobing Wu, Chuan Qin, Jin Qi, Shibin Ma, Huiyuan Zhang, Qingli Kong, Dongqing Chen, Denian Ba, Wei He

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)365-379
Number of pages15
JournalNeurobiology of Disease
Volume14
Issue number3
DOIs
StatePublished - Dec 2003
Externally publishedYes

Fingerprint

Dependovirus
Amyloid Plaques
Alzheimer Disease
Vaccines
Immunization
Aptitude
Gliosis
Amyloid beta-Protein Precursor
Cholera Toxin
Brain
Amyloid
Cognition
Transgenic Mice
Dementia
Protein Isoforms
Vaccination
Immunoglobulin G
Amino Acids
Serum
Genes

ASJC Scopus subject areas

  • Neurology

Cite this

A novel recombinant adeno-associated virus vaccine reduces behavioral impairment and β-amyloid plaques in a mouse model of Alzheimer's disease. / Zhang, Jianmin; Wu, Xiaobing; Qin, Chuan; Qi, Jin; Ma, Shibin; Zhang, Huiyuan; Kong, Qingli; Chen, Dongqing; Ba, Denian; He, Wei.

In: Neurobiology of Disease, Vol. 14, No. 3, 12.2003, p. 365-379.

Research output: Contribution to journalArticle

Zhang, Jianmin ; Wu, Xiaobing ; Qin, Chuan ; Qi, Jin ; Ma, Shibin ; Zhang, Huiyuan ; Kong, Qingli ; Chen, Dongqing ; Ba, Denian ; He, Wei. / A novel recombinant adeno-associated virus vaccine reduces behavioral impairment and β-amyloid plaques in a mouse model of Alzheimer's disease. In: Neurobiology of Disease. 2003 ; Vol. 14, No. 3. pp. 365-379.
@article{ff8323ebda9f4c3894c28c01050cb5ac,
title = "A novel recombinant adeno-associated virus vaccine reduces behavioral impairment and β-amyloid plaques in a mouse model of Alzheimer's disease",
abstract = "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.",
author = "Jianmin Zhang and Xiaobing Wu and Chuan Qin and Jin Qi and Shibin Ma and Huiyuan Zhang and Qingli Kong and Dongqing Chen and Denian Ba and Wei He",
year = "2003",
month = "12",
doi = "10.1016/j.nbd.2003.07.005",
language = "English (US)",
volume = "14",
pages = "365--379",
journal = "Neurobiology of Disease",
issn = "0969-9961",
publisher = "Academic Press Inc.",
number = "3",

}

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

VL - 14

SP - 365

EP - 379

JO - Neurobiology of Disease

JF - Neurobiology of Disease

SN - 0969-9961

IS - 3

ER -