Cerebrospinal Fluid Biomarkers in Cerebral Amyloid Angiopathy With and Without Spontaneous Lobar Hemorrhage

Cerebral amyloid angiopathy (CAA) typically presents as spontaneous lobar intracerebral hemorrhage (ICH) or cognitive impairment. While the Boston criteria 2.0 aid CAA diagnosis in ICH, detecting nonhemorrhagic cases remains challenging. Cerebrospinal fluid (CSF) biomarkers may offer valuable diagnostic support. This study aimed to evaluate CSF Aβ40, Aβ42, total-τ, phosphorylated-τ, Aβ42/Aβ40, and phosphorylated-τ/Aβ42 in patients with CAA with and without symptomatic ICH. This prospective observational study recruited patients with CAA from the cerebrovascular clinic of Fondazione IRCCS Istituto Neurologico Carlo Besta (Milan, Italy) from January 2021 to June 2024. Patients underwent T2*-weighted magnetic resonance imaging and lumbar puncture, with CSF biomarkers measured via Lumipulse. Participants were grouped into CAA-ICH+ (prior symptomatic lobar ICH) and CAA-ICH-. Fifty-four patients were included: 35 CAA-ICH+ (37.1% women) and 19 CAA-ICH- (52.4% men). Groups were similar in mean age at lumbar puncture (63.8 versus 67.9 years) and cognitive impairment prevalence (57.1% versus 47.4%). Median CSF Aβ40 level was significantly lower in CAA-ICH+ than in CAA-ICH- (4355 versus 6507 pg/mL, P<0.001). Median CSF Aβ42 level, although reduced in the entire CAA population analyzed, did not differ significantly between the 2 groups (245 versus 303 pg/mL, P=0.09). Other CSF biomarkers levels were comparable between CAA-ICH+ and CAA-ICH-: total-τ (P=0.28), phosphorylated-τ (P=0.16), Aβ42/Aβ40 (P=0.14), and phosphorylated-τ/Aβ42 (P=0.93). CSF Aβ40 is significantly lower in patients with CAA with prior ICH. Amyloid dysregulation in CAA may follow distinct pathological trajectories depending on previous ICH. CSF Aβ40 shows promise as a biomarker for CAA and merits further studies to explore its prognostic value in disease progression. URL: https://www.clinicaltrials.gov; Unique identifier: NCT04204642.