Amyloid-Related Imaging Abnormalities (ARIA)

Introduction

Amyloid Related Imaging Abnormalities (Aria) is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

Overview

Introduction

Amyloid Related Imaging Abnormalities (Aria) is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

Overview

Amyloid-Related Imaging Abnormalities (ARIA) are MRI findings observed in patients receiving anti-amyloid immunotherapy for [Alzheimer's disease](/diseases/alzheimers-disease). ARIA encompasses two subtypes — ARIA-E (edema/effusion) and ARIA-H (hemorrhage/hemosiderosis) — and represents the most significant safety concern associated with monoclonal antibodies targeting [amyloid-beta](/proteins/amyloid-beta) (Abeta), including [lecanemab](/therapeutics/lecanemab) (Leqembi), [donanemab](/therapeutics/donanemab) ([Kisunla](/entities/donanemab)), and aducanumab (Aduhelm) ([Sperling et al., 2011](https://doi.org/10.1016/j.jalz.2011.05.2351); [Sperling et al., 2019](https://pubmed.ncbi.nlm.nih.gov/31219218/)). [@van2023] [@hampel2023]

Understanding ARIA is critical as [anti-amyloid therapeutics](/therapeutics/anti-amyloid-therapeutics) enter routine clinical practice. While most cases are asymptomatic and resolve with appropriate management, severe ARIA can cause serious neurological complications and, rarely, death. The emergence of ARIA as a clinical entity has reshaped how anti-amyloid therapies are administered and monitored. [@hampel2023] [@sims2023]

Types of ARIA

ARIA-E (Edema/Effusion)

ARIA-E refers to amyloid-related imaging abnormalities with edema or sulcal effusion, appearing as hyperintense signal on T2-weighted FLAIR MRI sequences ([Barakos et al., 2022](https://doi.org/10.3174/ajnr.A7586)): [@sims2023] [@cummings2023]

• Imaging appearance: Patchy or confluent hyperintensity in brain parenchyma (vasogenic edema) and/or sulcal effusion (fluid in the sulci and subarachnoid space)
• Most common locations: Posterior brain regions (occipital and parietal lobes), though any cortical region may be affected
• Temporal pattern: Usually occurs within the first 3-6 months of treatment, most commonly before the 5th infusion
• Resolution: Typically resolves within 3-4 months with treatment suspension; can recur upon re-initiation
• Incidence: 10-35% depending on drug, dose, and patient population [@cummings2023]

ARIA-H (Hemorrhage/Hemosiderosis)

ARIA-H encompasses hemorrhagic or hemosiderotic changes detected on susceptibility-weighted imaging (SWI) or T2*-weighted gradient echo MRI: [@wang2025]

• Cerebral microbleeds (CMBs): Small, round, hypointense lesions representing focal hemosiderin deposits
• Cortical superficial siderosis (cSS): Linear hypointensities along the cortical surface
• Larger intracerebral hemorrhages: Rare but can be severe or fatal
• Incidence: 5-31% in clinical trials; ARIA-H microbleeds are more common than cSS [@cogswell2022]

ARIA-E and ARIA-H Co-occurrence

The two subtypes frequently co-occur — approximately 40-50% of patients with ARIA-E also develop ARIA-H. ARIA-H may persist after ARIA-E resolves, as hemosiderin deposits are permanent. [@cogswell2025] [@cogswell2022]

Pathophysiology

Vascular Amyloid Clearance Mechanism

The leading hypothesis links ARIA to the interaction between anti-amyloid antibodies and [cerebral amyloid angiopathy](/diseases/cerebral-amyloid-angiopathy) (CAA) ([Greenberg et al., 2017](https://pubmed.ncbi.nlm.nih.gov/28669190/); [Barakos et al., 2022](https://doi.org/10.3174/ajnr.A7586)): [@zimmer2025] [@cogswell2025]

Immunological Mechanisms

Additional immunological processes contribute to ARIA: [@zimmer2025]

• Fc-mediated effector functions: Antibody Fc regions engage [Microglia:

• Baseline MRI before treatment initiation
• MRI before the 3rd, 5th, 7th, and 14th infusions (approximately weeks 4, 8, 12, and 26)
• Additional imaging if symptoms develop

• Baseline MRI
• MRI before the 3rd, 4th, and 5th infusions (approximately months 2, 3, and 4)
• Additional imaging as clinically indicated

Treatment Algorithm for ARIA

Asymptomatic ARIA-E: [@aria]

• Consider temporary treatment suspension
• Repeat MRI in 2-4 months
• Resume treatment once ARIA-E has radiographically resolved

• Suspend treatment
• Consider corticosteroids (high-dose methylprednisolone or oral prednisone) for significant edema
• Monitor with serial MRI every 4-8 weeks until resolution
• Resume treatment only after complete radiographic resolution and symptom resolution

• ≤4 new microbleeds: May continue with enhanced monitoring
• 5-9 new microbleeds: Consider suspension; reassess with follow-up imaging
• ≥10 new microbleeds or any macrohemorrhage: Permanently discontinue

• Recurrent symptomatic ARIA-E
• Severe ARIA-E not resolving within expected timeframe
• Macrohemorrhage >1 cm
• ≥10 new microbleeds

ARIA by Drug

Lecanemab (Leqembi)

[Lecanemab](/therapeutics/lecanemab) is a humanized monoclonal antibody targeting soluble [Aβ](/proteins/amyloid-beta) protofibrils, approved by the FDA in January 2023 (accelerated) and July 2023 (traditional approval), and by the EMA in late 2024:

• CLARITY-AD trial (n=1,795): ARIA-E incidence 12.6%, ARIA-H microbleeds 17.3%, cSS 14.0%
• Symptomatic ARIA-E: 2.8%; most cases resolved within 4 months
• Three deaths potentially related to ARIA (including in patients on anticoagulants)
• [APOE ε4](/proteins/apoe)

Brain Atlas Resources

• Allen Human Brain Atlas: [Amyloid-Related Imaging Abnormalities expression search](https://human.brain-map.org/microarray/search/show?search_term=Amyloid-Related+Imaging+Abnormalities)
• Allen Mouse Brain Atlas: [Amyloid-Related Imaging Abnormalities search](https://mouse.brain-map.org/search/index.html?query=Amyloid-Related+Imaging+Abnormalities)
• Allen Cell Type Atlas: [Transcriptomic cell type reference](https://portal.brain-map.org/atlases-and-data/rnaseq)
• BrainSpan Developmental Transcriptome: [Amyloid-Related Imaging Abnormalities developmental expression](https://www.brainspan.org/rnaseq/search/index.html?search_term=Amyloid-Related+Imaging+Abnormalities)

See Also

• [Neurodegenerative Diseases](/diseases)
• [Disease Mechanisms](/mechanisms)
• [All Pages](/all-pages)

External Links

• [PubMed](https://pubmed.ncbi.nlm.nih.gov/)

Background

The study of Amyloid Related Imaging Abnormalities (Aria) has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.

Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.

References

Pathway Diagram

The following diagram shows the key molecular relationships involving Amyloid-Related Imaging Abnormalities (ARIA) discovered through SciDEX knowledge graph analysis: