Amyloid PET Burden, CSF Biomarkers, and APOE Genotype in People With Iatrogenic and Sporadic Cerebral Amyloid Angiopathy.

BACKGROUND AND

OBJECTIVES

Iatrogenic cerebral amyloid angiopathy (iCAA) is a rare form of CAA believed to result from β-amyloid (Aβ) transmission during neurosurgical procedures. We aimed to compare amyloid PET burden, CSF biomarkers, and APOE genotype between iCAA and sporadic CAA (sCAA).

METHODS

In this single-center, cross-sectional study, adults fulfilling diagnostic criteria for probable sCAA or iCAA who underwent amyloid PET and CSF assessment between 2021 and 2024 were included. Amyloid burden was quantified using Centiloid scaling of 18Fflutemetamol or 18Fflorbetaben PET scans. CSF Aβ42, Aβ40, Aβ42/Aβ40 ratio, p-tau181, and total tau (t-tau) were measured with Lumipulse assays. Multivariable regression adjusted for age and sex examined associations with Centiloid values.

RESULTS

Ninety-five patients were included (24 with iCAA, 71 with sCAA; median age 56.5 vs 70 years). Patients with iCAA showed significantly higher amyloid deposition (median Centiloid 57.3 vs 30.5; p = 0.0026). iCAA diagnosis was independently associated with +34.99 Centiloid units (95% CI 15.25-54.74; p = 0.001) after adjusting for age and sex. In patients with sCAA, Centiloid values correlated inversely with CSF Aβ42 and Aβ42/Aβ40 ratio, whereas no significant correlations were observed in patients with iCAA. APOE ε4 was markedly less frequent in iCAA (4.5% vs 34.2%).

DISCUSSION: Patients with iCAA exhibit higher amyloid burden and a distinct biomarker profile compared with those with sCAA, supporting a divergent-possibly exogenous-mechanism of amyloid propagation.

TRIAL REGISTRATION INFORMATION: SENECA, ClinicalTrials.gov Identifier: NCT04204642 (submitted on December 19, 2019).