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-β protein (Aβ) and vascular pathological findings to elucidate the mechanisms of Aβ elimination from the brain in CAA-ri.

Methods:

We examined Aβ₄₀ and Aβ₄₂ 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 Aβ₄₀ and Aβ₄₂ 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 Aβ₄₀ and Aβ₄₂ levels in the CSF showed no significant difference between pre-treatment CAA-ri (Aβ40, 6837 pg/ml; Aβ₄₂, 324 pg/ml) and AD-CAA (Aβ₄₀, 7669 pg/ml, p = 0.345; Aβ₄₂, 355 pg/ml, p = 0.760). Aβ₄₀ and Aβ₄₂ levels in patients with post-treatment CAA-ri (Aβ40, 1770 pg/ml, p = 0.056; Aβ₄₂, 167 pg/ml, p = 0.006) were lower than those in patients with pre-treatment CAA-ri. Regarding Aβ₄₀ and Aβ₄₂ positive arteries, acute CAA-ri cases showed a higher frequency of partially Aβ-deposited blood vessels than postmortem CAA-ri cases (Aβ₄₀, 20.8% versus 3.9%, p = 0.0714; Aβ₄₂, 27.4% versus 2.0%, p = 0.0714, respectively).

Conclusion:

Lower levels of CSF Aβ₄₀ and Aβ₄₂ could be biomarkers for the cessation of inflammation in CAA-ri reflecting the recovery of the intramural periarterial drainage pathway and vascular function.

Search results

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