Reduction of amyloid beta by Aβ3-10-KLH vaccine also decreases tau pathology in 3×Tg-AD mice

Hui-Yi Zhang; Kun Zhu; Yuan Meng; Li Ding; Jin-Chun Wang; Wen-Chao Yin; Yi Yan; Yun-Peng Cao

doi:10.1016/j.brainresbull.2018.07.019

Reduction of amyloid beta by Aβ3-10-KLH vaccine also decreases tau pathology in 3×Tg-AD mice

Brain Res Bull. 2018 Sep:142:233-240. doi: 10.1016/j.brainresbull.2018.07.019. Epub 2018 Aug 2.

Authors

Hui-Yi Zhang¹, Kun Zhu¹, Yuan Meng², Li Ding³, Jin-Chun Wang⁴, Wen-Chao Yin⁵, Yi Yan⁶, Yun-Peng Cao⁷

Affiliations

¹ Department of Neurology, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China.
² Department of Geriatrics, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China.
³ Department of Neurology, The Second Affiliated Hospital of Dalian Medical University, Dalian 116000, Liaoning Province, China.
⁴ Department of Neurology, Shenyang Fifth People Hospital, Shenyang 110001, Liaoning Province, China.
⁵ Department of Neurology, Dalian Municipal Central Hospital Affiliated of Dalian Medical University, Dalian 116000, Liaoning Province, China.
⁶ Department of Neurology, Central Hospital Affiliated to ShenYang Medical College, Shenyang 110001, Liaoning Province, China.
⁷ Department of Neurology, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China. Electronic address: ypengcao@yahoo.com.

PMID: 30077729
DOI: 10.1016/j.brainresbull.2018.07.019

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive amyloid-β (Aβ) accumulation, neurofibrillary tangles (NFTs) formation and synaptic alterations. Active immunotherapy is regarded as one of the most promising strategies for AD prevention and treatment. In this research, we used APPswe/PS1M146 V/TauP301 L triple transgenic (3×Tg-AD) mice, in which the pathological changes are the most similar to those in AD patients. The Aβ 3-10 -keyhole limpet haemocyanin (KLH) vaccine was administered to mice at 1 month, and no AD-associated changes were detected at that time. The vaccine effectively mitigated AD-like pathology and cognitive dysfunction in the 3×Tg-AD mice. Both soluble and insoluble Aβ and tau protein in the brain tissues of the 3×Tg-AD mice were significantly decreased after the administration of Aβ 3-10 -KLH. In addition, the level of phosphorylated tau also decreased following removal of the Aβ pathological changes.

Keywords: Alzheimer’s disease; Aβ; Aβ3-10-KLH vaccine; Tau phosphorylation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alzheimer Disease / metabolism*
Alzheimer Disease / pathology
Alzheimer Disease / therapy*
Alzheimer Vaccines / therapeutic use*
Amyloid beta-Peptides / genetics
Amyloid beta-Peptides / metabolism
Animals
Brain / metabolism
Brain / pathology
Cognitive Dysfunction / metabolism
Cognitive Dysfunction / pathology
Cognitive Dysfunction / therapy
Female
Humans
Immunization*
Male
Mice, Inbred C57BL
Mice, Transgenic
Random Allocation
Vaccines / therapeutic use*
tau Proteins / genetics
tau Proteins / metabolism

Substances

Abeta3-10-KLH vaccine
Alzheimer Vaccines
Amyloid beta-Peptides
MAPT protein, human
Mapt protein, mouse
Vaccines
tau Proteins