Cerebrospinal Fluid Biomarkers and Amyloid- Elimination from the Brain in Cerebral Amyloid Angiopathy-Related Inflammation

Background: Cerebrospinal fluid (CSF) biomarkers in patients with cerebral amyloid angiopathy-related inflammation (CAA-ri) have demonstrated inconsistent results. Objective: We investigated the relationship between CSF amyloid-beta protein (A beta) and vascular pathological findings to elucidate the mechanisms of A beta elimination from the brain in CAA-ri. Methods: We examined A beta(40) and A beta(42) levels in CSF samples in 15 patients with CAA-ri and 15 patients with Alzheimer's disease and cerebral amyloid angiopathy (AD-CAA) using ELISA as a cross-sectional study. Furthermore, we pathologically examined A beta(40) and A beta(42) depositions on the leptomeningeal blood vessels (arteries, arterioles, and veins) using brain biopsy samples from six patients with acute CAA-ri and brain tissues of two autopsied patients with CAA-ri. Results: The median A beta(40) and A beta(42) levels in the CSF showed no significant difference between pre-treatment CAA-ri (A beta(40), 6837 pg/ml; A beta(42), 324 pg/ml) and AD-CAA (A beta(40), 7669 pg/ml, p = 0.345; A beta(42), 355 pg/ml, p = 0.760). A beta(40) and A beta(42) levels in patients with post-treatment CAA-ri (A beta(40), 1770 pg/ml, p = 0.056; A beta(42), 167 pg/ml, p = 0.006) were lower than those in patients with pre-treatment CAA-ri. Regarding A beta(40) and A beta(42) positive arteries, acute CAA-ri cases showed a higher frequency of partially A beta-deposited blood vessels than postmortem CAA-ri cases (A beta(40), 20.8% versus 3.9%, p = 0.0714; A beta(42), 27.4% versus 2.0%, p = 0.0714, respectively). Conclusion: Lower levels of CSF A beta(40) and A beta(42) could be biomarkers for the cessation of inflammation in CAA-ri reflecting the recovery of the intramural periarterial drainage pathway and vascular function.