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Suppression of AIMP1 protects cognition in Alzheimer's disease model mice 3xTg-AD

 Sooah Jang  ;  Jung Ho Lee  ;  Bo Kyung Sohn  ;  Eosu Kim  ;  Sang Gyu Park  ;  Kang Jun Yoon  ;  Minsun Park  ;  Eun Woo Kim  ;  Jihyeon Jeong  ;  Jun-Young Lee  ;  Chul Hoon Kim  ;  Kee Namkoong 
 Neuroreport, Vol.28(2) : 82-86, 2017 
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Issue Date
Aged ; Aged, 80 and over ; Alzheimer Disease/blood ; Alzheimer Disease/complications* ; Alzheimer Disease/genetics ; Alzheimer Disease/pathology ; Amyloid beta-Protein Precursor/genetics ; Animals Antibodies/therapeutic use ; Avoidance Learning/drug effects ; Brain/diagnostic imaging ; Cognition Disorders/metabolism* ; Cognition Disorders/prevention & control* ; Cytokines/immunology ; Cytokines/metabolism* ; Disease Models, Animal ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Memory Disorders/etiology ; Mental Status Schedule ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Middle Aged ; Mutation/genetics ; Presenilin-1/genetics ; Rotarod Performance Test ; tau Proteins/genetics
Alzheimer’s disease ; aminoacyl-tRNA synthetase complex interacting multifunctional protein 1 ; antiaminoacyl-tRNA synthetase complex interacting multifunctional protein 1 antibody ; neuroinflammation
Neuroinflammation has been raised as a candidate of unifying pathogenesis and a target of a disease-modifying strategy for Alzheimer's disease (AD). Aminoacyl-tRNA synthetase complex (ARS)-interacting multifunctional protein 1 (AIMP1) is a cytokine that is known to amplify the actions of tumor necrosis factor-α and to be involved in microglial activation and neuronal death. In this respect, AIMP1 could be a plausible target for the treatment of AD. Therefore, we aimed to examine whether anti-AIMP1 antibody could exert therapeutic effects against cognitive impairment using 3xTg-AD mice. Through the passive avoidance test, we found that an intraperitoneal injection of anti-AIMP1 antibody over 4 weeks was effective in protecting memory function in 3xTg-AD mice (16 weeks old). In addition, to address the translational implications of AIMP1, we measured blood AIMP1 levels in patients with AD (n=22), mild cognitive impairment (n=25), and normal cognition (n=23). Blood AIMP1 levels were associated negatively with global cognitive function and were significantly higher in individuals with a higher degree of medial temporal lobe atrophy, which is one of the representative clinical markers of AD. Our results suggested a possible association of AIMP1 with AD pathogenesis, as well as the potential of the anti-AIMP1 antibody as a novel therapeutic option for AD.
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1. College of Medicine (의과대학) > Dept. of Psychiatry (정신과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
Yonsei Authors
김어수(Kim, Eosu) ORCID logo https://orcid.org/0000-0001-9472-9465
김철훈(Kim, Chul Hoon) ORCID logo https://orcid.org/0000-0002-7360-429X
남궁기(Namkoong, Kee) ORCID logo https://orcid.org/0000-0003-1400-8057
이정호(Lee, Jeong Ho)
장수아(Jang, Soo Ah)
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