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Sci Rep. 2018 Nov 26;8(1):17369. doi: 10.1038/s41598-018-35030-1.

Bee venom phospholipase A2 ameliorates Alzheimer's disease pathology in Aβ vaccination treatment without inducing neuro-inflammation in a 3xTg-AD mouse model.

Author information

1
Department of Physiology, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.
2
Department of Acupuncutre & Moxibustion Medicine, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.
3
Department of Anatomy-Pointology, College of Korean Medicine, Gachon University, Seongnam, 13120, Republic of Korea.
4
Division of RI-Convergence Research, Korea Institute Radiological and Medical Sciences, 75 Nowon-Gil, Gongneung-Dong, Nowon-Gu, Seoul, 01812, Republic of Korea.
5
Acupuncture and Meridian Science Research Center, College of Korean Medical Science Graduate School, Kyung Hee University, Seoul, Republic of Korea.
6
Department of Physiology, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea. hbae@khu.ac.kr.

Abstract

Alzheimer's disease (AD) is the most common form of dementia and is characterized by an imbalance between the production and clearance of amyloid-beta (Aβ) and tau proteins. Although vaccination against Aβ peptide results in a dramatic reduction in Aβ pathology in experimental mouse models, the initial clinical trial for an active Aβ vaccine was halted early due to the development of acute meningoencephalitis in 6% of the immunized patients, which likely involved a T-cell mediated pro-inflammatory response. In this study, we aimed to determine whether bee venom phospholipase A2 (bvPLA2) treatment would induce Tregs and ameliorate AD pathology without unwanted T cell-mediated inflammation. First, we investigated the effects of bvPLA2 on the inflammatory infiltration caused by Aβ vaccination. Inflammatory aggregates of CD3+ T lymphocytes and macrophages were found in the brains and spinal cords of mice treated with Aβ. However, administration of bvPLA2 dramatically eliminated central nervous system inflammation following Aβ immunization. In AD model mice (3xTg-AD mice), bvPLA2 administration significantly ameliorated cognitive deficits and reduced Aβ burdens in the brains of Aβ-vaccinated 3xTg-AD mice. Additionally, we examined brain glucose metabolism using positron emission tomography with 18F-2 fluoro-2-deoxy-D-glucose. Cerebral glucose uptake was considerably higher in the brains of Aβ-vaccinated 3xTg-AD mice that received bvPLA2 than those that did not. The present study suggests that the modulation of Treg populations via bvPLA2 treatment may be a new therapeutic approach to attenuate the progression of AD in conjunction with Aβ vaccination therapy without an adverse inflammatory response.

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