Abstract
Neurology. 2025 Nov 25;105(10):e214336. doi: 10.1212/WNL.0000000000214336. Epub 2025 Nov 5.
ABSTRACT
BACKGROUND AND OBJECTIVES: Blood-brain barrier (BBB) leakage may be an early step in the pathophysiology of cerebral amyloid angiopathy (CAA), possibly preceding hemorrhages. This exploratory study measured BBB leakage in vivo at the level of the leptomeningeal and small parenchymal vessels in patients with probable CAA. We hypothesized that BBB leakage from leptomeningeal and cortical small vessels would be higher in patients with CAA compared with controls and that leakage would be associated with hemorrhagic manifestations of CAA, that is, cortical superficial siderosis (cSS) and lobar cerebral microbleeds (CMBs).
METHODS: Patients with probable CAA without previous intracerebral hemorrhage and non-CAA patients with mild cognitive impairment from the memory clinic were recruited in this prospective observational exploratory study. Participants underwent 3T brain MRI with injection of a gadolinium-based contrast agent (Dotarem). Leakage from leptomeningeal vessels was assessed on postcontrast vs precontrast T2-fluid-attenuated inversion recovery as either focal or sulcal CSF enhancements. Dynamic contrast-enhanced scans were analyzed to quantify permeability-surface area product (PS): a measure of leakage from parenchymal small vessels.
RESULTS: Fourteen patients with CAA (mean age 67.7 ± 9.0 years; 57% female) and 7 non-CAA patients with mild cognitive impairment (mean age 70.1 ± 6.5 years; 29% female) were recruited. Focal CSF enhancements were observed similarly often in patients with CAA (7 [50%]) and non-CAA controls (4 [57%], p = 0.98), whereas sulcal CSF enhancements were only seen in patients with CAA (5 [36%] vs 0 [0%]). In patients with CAA, focal and sulcal CSF enhancement counts were associated with higher cSS volume (B = 2.61, p = 0.003; B = 1.02, p = 0.02), but not with CMBs. PS was numerically higher in the cortex in patients with CAA (5.08 ± 4.02 × 10-4 min-1) than in non-CAA controls (1.29 ± 4.08 × 10-4 min-1, p = 0.07), but it was not associated with CMB count or cSS volume (p > 0.67).
DISCUSSION: Leakage of gadolinium-based contrast agent through the BBB can be measured in vivo in CAA from the leptomeningeal vessels, and findings point to likely leakage from cortical small vessels as well. Leakage from leptomeningeal vessels was associated with cSS. Studies with follow-up data need to determine whether these measures could serve as a predictive biomarker in CAA.
PMID:41191838 | DOI:10.1212/WNL.0000000000214336