Cerebrospinal fluid cytokines and metalloproteinases in cerebral amyloid angiopathy-related inflammation.

Objectives To clarify pathomechanisms of cerebral amyloid angiopathy-related inflammation/vasculitis (CAA-ri). Methods We collected cerebrospinal fluid (CSF) samples of nine patients with CAA-ri of before (acute CAA-ri group) and after treatment (post-treatment CAA-ri group) and nine patients with CAA (CAA without inflammation group). We examined anti-amyloid β protein (Aβ) antibody titer by ELISA, and measured 27 Cytokines, nine matrix metalloproteinases (MMPs), and four tissue inhibitors of MMPs (TIMPs) by multiplexed fluorescent bead-based immunoassay. Results We demonstrated TIMP-2 (median) in CSF of the acute CAA-ri group (30994.49 pg/ml, P = 0.007) and the post-treatment CAA-ri group (36430.97 pg/ml, P = 0.001) was significantly elevated compared to that of the CAA without inflammation group (22013.58 pg/ml). TIMP-1 was also higher in the post-treatment CAA-ri group than that in the CAA without inflammation group (58167.75 pg/ml vs. 45770.03 pg/ml, P = 0.005). There was a significant positive correlation between TIMP-1 and anti-Aβ antibodies in CAA-ri (rs = 0.900, P = 0.037). Median MMP-2 tended to be higher in the acute and post-treatment CAA-ri groups (10619.82 pg/ml and 8396.98 pg/ml, respectively) than in the CAA without inflammation group (4436.34 pg/ml). Platelet-derived growth factor (PDGF)-BB levels before treatment were higher than those after treatment (median, 12.66 pg/ml vs. 6.39 pg/ml; P = 0.011) and correlated with the titer of anti-Aβ antibodies (rs = 0.900, P = 0.037). Conclusions Elevated levels of MMP-2, TIMP-1, and TIMP-2 might be related to the development of CAA-ri. Elevation of PDGF-BB could be a useful marker for clinical diagnosis of CAA-ri.