Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease (Aug 2025)
Cerebrospinal Fluid β‐Amyloid and τ Levels in Patients With Iatrogenic Cerebral Amyloid Angiopathy, Sporadic Cerebral Amyloid Angiopathy, Alzheimer Disease, and Controls
Abstract
Background Iatrogenic cerebral amyloid angiopathy (iCAA) is a subform of cerebral amyloid angiopathy caused by exposure to amyloid β. The aim of this study was to assess cerebrospinal fluid amyloid and τ concentrations in iCAA in comparison with sporadic cerebral amyloid angiopathy (sCAA), Alzheimer disease (AD), and controls. Methods We conducted a systematic literature review to identify patients with iCAA with published cerebrospinal fluid marker concentrations. We then analyzed the cerebrospinal fluid concentrations of amyloid β40, amyloid β42, total τ, and phosphorylated τ 181, comparing them with the corresponding data of patients with sCAA, AD, and controls from our previous work. Results The study included 25 patients with iCAA (age, 44±11 years), 31 patients with sCAA (age, 75±5 years), 28 patients with AD (age, 71±8 years) and 30 controls (age, 72±8 years) from 9 case descriptions and 1 cohort study. Amyloid β40 concentrations did not differ significantly between iCAA and the other groups. Amyloid β42 concentration was significantly higher in controls than iCAA and the other groups. The amyloid β42/40 ratio was higher in iCAA than in AD and higher in controls than sCAA and AD. Total τ concentrations were lower in controls than iCAA but did not differ significantly between iCAA, sCAA, and AD. Phosphorylated τ concentrations were not significantly different in iCAA compared with controls, significantly higher in sCAA, and highest in AD. Conclusions The observation that phosphorylated τ concentrations in iCAA are not different from controls led us to the hypothesis that iCAA is characterized by amyloid plaque formation largely without concomitant phosphorylated τ aggregation, which is well compatible with most published pathologic studies.
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