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Modulation of Alzheimer’s Disease Pathology by Collagen-Induced Rheumatoid Arthritis in APP/PS1 Mice

Other Title
콜라겐 유도에 의한 관절염이 치매동물의 병리기전에 미치는 영향에 관한 연구
Authors
박, 선미
Degree
Doctor (2012)
Abstract
Several evidences suggest that rheumatoid arthritis (RA) may enhance or reduce the progression of Alzheimer’s disease (AD). The present study was performed to directly explore the effects of collagen-induced rheumatoid arthritis (CIA) on cognitive function, amyloid plaque formation, microglial activation, and cerebrovascular pathology in the cortex and hippocampus of the double transgenic APP/PS1 mouse model for AD. Wild-type or APP/PS1 mice that received type II collagen (CII) in complete Freund’s adjuvant (CFA) at presymptomatic stage (2 months) or postsymptomatic stage (8.5 months) of age revealed characteristics of RA, such as joint swelling, synovitis, and cartilage and bone degradation 4 months later. Joint pathology was accompanied by sustained induction of IL-1β and TNF-α in plasma over 4 weeks after administration of CII in CFA.

In the presymptomatic stage, prior to the onset of plaque formation, CIA reduced levels of soluble and insoluble amyloid beta (Aβ peptides) and amyloid plaque formation in the cortex and hippocampus of APP/PS1 mice, which correlated with increased blood brain barrier disruption, Iba-1 or Mac-1 positive microglia, and CD45-positive microglia/macrophages. In contrast, CIA reduced survival and vessel density and length with features of cerebrovascular pathology including vascular segments, thinner vessels, and atrophic string vessels.

In the postsymptomatic stage, after the onset of amyloid plaque formation, CIA mice improved cognitive function behavior based on the performance in the MWM and the Y-Maze and reduced amyloid plaque pathology. Additionally CIA mice increased cerebrovascular pathology and mortality.

The present findings suggest that RA may exert beneficial effects against Aβ burden and harmful effects on cerebrovascular pathology and mortality in AD. However, the chronic systemic inflammation causes cerebrovascular pathology, which likely aggravates pathology and neurological deficit in APP/PS1 and possibly AD patients.
Keywords
Alzheimer’s disease (AD)Rheumatoid arthritis (RA)InflammationBlood-brain barrier (BBB)Amyloid beta (Aβ)
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Theses > School of Medicine / Graduate School of Medicine > Doctor
AJOU Authors
박, 선미
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