TY - JOUR
T1 - DNA immunization with HBsAg-based particles expressing a B cell epitope of amyloid β-peptide attenuates disease progression and prolongs survival in a mouse model of Alzheimer's disease
AU - Olkhanud, Purevdorj B.
AU - Mughal, Mohammed
AU - Ayukawa, Koichi
AU - Malchinkhuu, Enkhzol
AU - Bodogai, Monica
AU - Feldman, Neil
AU - Rothman, Sarah
AU - Lee, Jong Hwan
AU - Chigurupati, Srinivasulu
AU - Okun, Eitan
AU - Nagashima, Kunio
AU - Mattson, Mark P.
AU - Biragyn, Arya
PY - 2012/2/21
Y1 - 2012/2/21
N2 - Alzheimer's disease (AD) is an incurable and progressive neurodegenerative senile disorder associated with the brain accumulation of Aβ plaques. Although vaccines that reduce Aβ plaques can control AD, the rationale for their use at the onset of the disease remains debatable. Old humans and mice usually respond poorly to vaccines due to presumably age-related immunological impairments. Here, we report that by modifying vaccines, the poor responsiveness of old mice can be reversed. Unlike the Aβ peptide vaccine, DNA immunizations with the amino-terminal Aβ(1-11) fragment exposed on the surface of HBsAg particles elicit high levels of anti-Aβ antibody both in young and old mice. Importantly, in AD model 3xTgAD mice, the vaccine reduced Aβ plaques, ameliorated cognitive impairments and, surprisingly, significantly increased life span. Hence, we propose that vaccines targeting Aβ(1-11) can efficiently combat AD-induced pathological alterations and provide survival benefit in patients with AD.
AB - Alzheimer's disease (AD) is an incurable and progressive neurodegenerative senile disorder associated with the brain accumulation of Aβ plaques. Although vaccines that reduce Aβ plaques can control AD, the rationale for their use at the onset of the disease remains debatable. Old humans and mice usually respond poorly to vaccines due to presumably age-related immunological impairments. Here, we report that by modifying vaccines, the poor responsiveness of old mice can be reversed. Unlike the Aβ peptide vaccine, DNA immunizations with the amino-terminal Aβ(1-11) fragment exposed on the surface of HBsAg particles elicit high levels of anti-Aβ antibody both in young and old mice. Importantly, in AD model 3xTgAD mice, the vaccine reduced Aβ plaques, ameliorated cognitive impairments and, surprisingly, significantly increased life span. Hence, we propose that vaccines targeting Aβ(1-11) can efficiently combat AD-induced pathological alterations and provide survival benefit in patients with AD.
KW - Aβ
KW - Alzheimer's disease vaccine
KW - Life span
KW - Old age
UR - http://www.scopus.com/inward/record.url?scp=84862777017&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84862777017&partnerID=8YFLogxK
U2 - 10.1016/j.vaccine.2011.12.136
DO - 10.1016/j.vaccine.2011.12.136
M3 - Article
C2 - 22248819
AN - SCOPUS:84862777017
SN - 0264-410X
VL - 30
SP - 1650
EP - 1658
JO - Vaccine
JF - Vaccine
IS - 9
ER -