title: Prophylactic active immunization with a novel epitope vaccine improves cognitive ability by decreasing amyloid plaques and neuroinflammation in APP/PS1 transgenic mice.
abstract: Both amyloid-β peptide (Aβ) deposition and neuroinflammation are considered to be early events that play pivotal roles in Alzheimer's disease (AD) pathogenesis and its associated cognitive impairment. Prophylactic anti-Aβ active immunotherapy is a promising therapeutic strategy for AD, if the Aβ-specific autoimmune responses to self T cell epitopes of Aβ can be avoided. This can be achieved by the use of antigen, which contains the B cell epitope of Aβ and excludes the Aβ-specific T cell epitope. In this study, we developed a novel peptide epitope vaccine, Aβ3-10-KLH, by coupling the B cell epitope Aβ3-10 to keyhole limpet hemocyanin (KLH) as the carrier protein, and subcutaneously injected it into 2.5-month-old APP/PS1 transgenic mice. Aβ3-10-KLH immunization induced high levels of anti-Aβ antibodies and significantly improved cognitive ability in APP/PS1 transgenic mice. Immunohistochemistry and immunofluorescence revealed that Aβ3-10-KLH immunization significantly reduced cerebral amyloid plaque formation and alleviated gliosis. The results indicate that Aβ3-10-KLH immunization successfully rescued cognitive impairment in APP/PS1 transgenic mice via decreasing cerebral Aβ deposition and neuroinflammation. Aβ3-10-KLH may potentially be safe and effective for prevention and treatment of AD.
authors.affiliation: Department of Neurology, The First Affiliated Hospital of China Medical University, Shenyang City, Liaoning Province, China; Department of Neurology, The Second Affiliated Hospital of Dalian Medical University, Dalian City, Liaoning Province, China.
authors.forename: Li
authors.initials: L
authors.lastname: Ding
authors.affiliation: Department of Neurology, The First Affiliated Hospital of China Medical University, Shenyang City, Liaoning Province, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Meng
authors.affiliation: Department of Neurology, The First Affiliated Hospital of China Medical University, Shenyang City, Liaoning Province, China.
authors.forename: Hui-Yi
authors.initials: HY
authors.lastname: Zhang
authors.affiliation: Department of Neurology, The First Affiliated Hospital of China Medical University, Shenyang City, Liaoning Province, China.
authors.forename: Wen-Chao
authors.initials: WC
authors.lastname: Yin
authors.affiliation: Department of Neurology, The First Affiliated Hospital of China Medical University, Shenyang City, Liaoning Province, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yan
authors.affiliation: Department of Neurology, The First Affiliated Hospital of China Medical University, Shenyang City, Liaoning Province, China. Electronic address: dingding8766@163.com.
authors.forename: Yun-Peng
authors.initials: YP
authors.lastname: Cao
mesh_terms: D016229:Amyloid beta-Peptides / Q000276:immunology*; D000818:Animals; D001921:Brain / Q000276:immunology / Q000473:pathology*; D003071:Cognition / Q000502:physiology*; D000939:Epitopes / Q000276:immunology*; D005911:Gliosis / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D006433:Hemocyanins / Q000276:immunology; D007249:Inflammation / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000276:immunology*; D058225:Plaque, Amyloid / Q000276:immunology*; D053764:Presenilin-1; D014611:Vaccination / Q000379:methods*; D014612:Vaccines / Q000276:immunology*
chemical_list: D016229:Amyloid beta-Peptides; D000939:Epitopes; D010446:Peptide Fragments; D053764:Presenilin-1; D014612:Vaccines; C000625577:amyloid beta-protein (3-10); D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin
keywords: Alzheimer’s disease; Amyloid-β peptide; Epitope vaccine; Gliosis; Neuroinflammation