2025 年 42 巻 3 号 p. 414-417
Amyloid–related imaging abnormalities (ARIA) are complications of anti–amyloid beta (Aβ) monoclonal antibody therapy for Alzheimer disease (AD). They are classified into ARIA–E (edema/effusion), which is characterized by vasogenic edema of the cerebral parenchyma and exudation of plasma components into the cerebral sulci, and ARIA–H (microhemorrhage/hemosiderosis), which is characterized by microbleeds and cortical superficial siderosis. The following pathogenesis of ARIA has been postulated. When anti–Aβ antibodies are administered to AD, 1) Aβ plaques in the brain parenchyma are dissolved and expelled through the intramural peri–arterial drainage, exacerbating cerebral amyloid angiopathy (CAA) ; 2) blood vessels are damaged as antibodies remove Aβ deposited in the vessels ; 3) blood vessels are damaged by an excessive inflammatory response such as the activation of microglia and complement cascade. These pathological conditions cause the blood–brain barrier (BBB) breakdown and increased vascular permeability, leading to leakage of plasma and blood components, causing ARIA.
CAA–related inflammation (CAA–ri) is characterized by acute or subacute decreased level of consciousness, seizures, headache, focal neurologic symptoms/signs, and is characterized by vasogenic edema in the cerebral white matter and lobar microbleeds on brain MRI. Pathologically, CAA–positive cortical and/or leptomeningeal vessel with associated perivascular or transmural inflammation. Increased vascular permeability and immune response to vascular Aβ with inflammation may be the common pathogenesis of ARIA and CAA–ri, and one might say that “ARIA is iatrogenic CAA-ri.”
Other differentiating conditions of ARIA include reversible vasogenic edema in CAA and posterior reversible encephalopathy syndrome (PRES). In CAA, autoregulation of cerebral circulation is lost, and vascular Aβ deposition can damage the BBB causing vascular leakage and resulting in reversible vasogenic edema. PRES is thought to be caused by hypertension, cerebral hyperperfusion, and endothelial dysfunction, which leads to BBB breakdown and increased vascular permeability, resulting in vasogenic edema and bleeding. It has been suggested that ARIA and PRES may be partially overlapping conditions.
