Effects of collagen-induced rheumatoid arthritis on amyloidosis and microvascular pathology in APP/PS1 mice.
BACKGROUND
Evidence suggests 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 amyloid plaque formation, microglial activation, and microvascular 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 2 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.


RESULTS
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-positive microglia, and CD45-positive microglia/macrophages. In contrast, CIA reduced vessel density and length with features of microvascular pathology, including vascular segments, thinner vessels, and atrophic string vessels.


CONCLUSIONS
The present findings suggest that RA may exert beneficial effects against Aβ burden and harmful effects on microvascular pathology in AD.
Department of Pharmacology, Ajou University School of Medicine, Suwon, South Korea.
Sun Mi
SM
Park
Jin Hee
JH
Shin
Gyeong Joon
GJ
Moon
Sung Ig
SI
Cho
Yong Beom
YB
Lee
Byoung Joo
BJ
Gwag
D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000686:Amyloidosis / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D000818:Animals; D001169:Arthritis, Experimental / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D024043:Collagen Type II / Q000633:toxicity; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D008833:Microcirculation / Q000235:genetics; D053764:Presenilin-1 / Q000235:genetics*
D016564:Amyloid beta-Protein Precursor; D024043:Collagen Type II; C508853:PSEN1 protein, human; D053764:Presenilin-1