Cerebrospinal Fluid Beta‐Amyloid Concentration and Clinical and Radiographic Manifestations of Cerebral Amyloid Angiopathy

Abstract

Background Cerebral amyloid angiopathy (CAA) is driven by vascular Aβ (amyloid‐beta) deposition, which can be detected as reduced Aβ species in cerebrospinal fluid (CSF). We sought to identify relationships between CSF Aβ and tau concentrations and various manifestations of CAA. Methods This is a retrospective cross‐sectional single‐center study of patients diagnosed with CAA per Boston Criteria version 2.0, had magnetic resonance imaging brain scans, and underwent CSF testing for Aβ and tau concentrations between 2008 and 2022. Associations between clinical/magnetic resonance imaging features and CSF biomarker concentrations were investigated with univariate and multivariate models. Results We identified 31 patients aged 69.6±8.4 years, of whom 20 presented with cognitive complaints, 9 with CAA‐related macrohemorrhage (lobar intraparenchymal or convexity subarachnoid hemorrhage), and 2 with transient focal neurological episodes. Presence of macrohemorrhage (301.8±112 pg/mL versus 400.9±123 pg/mL, P=0.029), cortical superficial siderosis (309.6±131 mg/dL versus 412.3±100 pg/mL, P=0.021), and severe enlarged perivascular spaces in centrum semiovale (285.8±91 pg/mL versus 428.3±117 pg/mL, P<0.001) were associated with lower Aβ42 concentrations. Aβ42 concentrations inversely correlated with the number of these manifestations, being lowest in patients having all three. Patients with cognitive complaints had higher t‐tau (total tau; 551±320 pg/mL versus 317.2±141 pg/mL, P=0.03) and trended toward having higher p‐tau (phosphorylated tau at threonine 181) concentrations (75.69±39 pg/mL versus 49.24±22 pg/mL, P=0.05). Conclusions Lower CSF Aβ42, suggesting higher amyloid burden, is associated with CAA‐related macrohemorrhages and severe enlarged perivascular spaces in centrum semiovale, suggesting potential mechanistic links and CSF Aβ42 as a potential biomarker for progression of CAA. CSF tau concentrations are linked to cognitive complaints, likely representing comorbid Alzheimer disease pathology.

Keywords

• amyloid
• cerebral amyloid angiopathy
• cerebrospinal fluid biomarkers
• cortical superficial siderosis
• perivascular spaces in centrum semiovale
• intracerebral hemorrhage