Cerebrospinal fluid biomarkers for cerebral amyloid angiopathy with non-hemorrhagic imaging marker

Reduced cerebrospinal fluid (CSF) amyloid beta (Aβ) 40 has been reported in cerebral amyloid angiopathy (CAA) diagnosed by hemorrhagic magnetic resonance imaging (MRI) markers. Whether similar alterations occur when fulfilling Boston Criteria 2.0 solely through non-hemorrhagic markers remains unclear.

We analyzed 358 memory clinic patients undergoing MRI and CSF assessment. CAA was categorized by hemorrhagic markers (CAA 1.5 H) or exclusively non-hemorrhagic markers (CAA 2.0 NH) per Boston Criteria 1.5 and 2.0, respectively. Primary comparison of CSF-Aβ40 between CAA groups was complemented by secondary (Aβ42, phosphorylated tau [p-tau181], total tau [t-tau]) and exploratory analyses including Alzheimer's disease (AD), mild cognitive impairment (MCI), and healthy controls, adjusted for age, sex, MRI characteristics, and assay type.

Sixty-five patients were reclassified as CAA 2.0 NH. Aβ40 was higher in CAA 2.0 NH than CAA 1.5 H (15,808 vs. 13,792 pg/ml, p = 0.033) and did not differ from AD, MCI, or controls. p-tau181 reached significance after adjustment (p = 0.010), likely reflecting AD co-pathology. However, within CAA-2.0-NH, patients with AD CSF profile showed Aβ40 comparable to hemorrhagic CAA.

Non-hemorrhagic imaging markers alone were not associated with characteristic CAA-related CSF alterations, suggesting biological heterogeneity, limited specificity, or lesion type-dependent variability.