Amyloid-Related Imaging Abnormalities and β-Amyloid-Targeting Antibodies: A Systematic Review.
Abstract
Importance After more than a decade of research and development of clinical trials testing anti-β-amyloid monoclonal antibodies (mAbs), extensive experience has been gained regarding the effects of these treatments in patients with Alzheimer disease (AD). On the verge of an expected large-scale introduction in the clinical setting after the recent US Food and Drug Administration approval of aducanumab, shared knowledge regarding amyloid-related imaging abnormalities (ARIAs) is of paramount importance. Objective To summarize available evidence on ARIAs from randomized clinical trials (RCTs) testing anti-β-amyloid mAbs in patients with AD and to provide a comprehensive update about risk factors, clinical correlates, and implications for withholding and reinitiating treatment. Evidence review In this systematic review, a literature search of MEDLINE/PubMed, Embase, and Cochrane Library and a search of ClinicalTrials.gov were conducted through September 15, 2021. Publications describing RCTs, secondary analyses of RCT data, and case reports of ARIAs were included. Strengths of clinical data were graded according to the Oxford Centre for Evidence-Based Medicine. Findings Twenty-two RCTs, 11 secondary analyses of RCTs, and 1 case report, including in total 15 508 adult patients (8483 women [54.7%]; mean [SD] age, 69.6 [8.3] years) were selected for inclusion. Signal alterations that included parenchymal edema and sulcal effusion leading to transient hyperintensities on fluid-attenu…
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ApoE ε4 status has gained direct clinical relevance in the anti-amyloid era.
“Importantly, ApoE ε4 status has gained direct clinical relevance in the anti-amyloid era”
From Plasma ApoE proteotyping for ApoE ε4 stratification in the anti-amyloid therapies era (2026) · cites this paper as [2]
ε4 carriers, particularly ε4 homozygotes, exhibit a substantially increased risk of amyloid-related imaging abnormalities (ARIA) during treatment with anti-amyloid monoclonal antibodies.
“ε4 carriers, particularly ε4 homozygotes, exhibit a substantially increased risk of amyloid-related imaging abnormalities (ARIA) during treatment with anti-amyloid monoclonal antibodies [2, 5, 8].”
From Plasma ApoE proteotyping for ApoE ε4 stratification in the anti-amyloid therapies era (2026) · cites this paper as [2]
In the era of disease-modifying anti-amyloid therapies, ApoE ε4 carriers, particularly ε4 homozygotes, exhibit a substantially increased risk of ARIAs.
“In the era of disease-modifying anti-amyloid therapies, ApoE ε4 status has become directly actionable, as ε4 carriers, particularly ε4 homozygotes, exhibit a substantially increased risk of ARIAs [2, 33].”
From Plasma ApoE proteotyping for ApoE ε4 stratification in the anti-amyloid therapies era (2026) · cites this paper as [2]
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Emerging diagnostics and therapeutics for Alzheimer disease
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Amyloid-Related Imaging Abnormalities: An Update
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“The ARIA-E and ARIA-H are thought to be expressions of an increased vascular fragility and leakage of proteinaceous fluid and erythrocytes caused by the therapeutic effect of monoclonal antibodies [12].”
Plasma ApoE proteotyping for ApoE ε4 stratification in the anti-amyloid therapies era
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Self-citation
- Authors
- Filippi, M., Cecchetti, G., Spinelli, E. G., Vezzulli, P., Falini, A., & Agosta, F.
- Affiliations
- Vita-Salute San Raffaele University (IT)
- IRCCS Ospedale San Raffaele (IT)
- ORCID
- Venue
- JAMA Neurology
- Publisher
- American Medical Association (AMA)
- Published
- 2022-03-01
- Volume
- 79
- Issue
- 3
- Pages
- 291
- ISSN
- 2168-6149 (ISSN-L)
- OpenAlex
- W4210419282
- Cited by
- 189
- References
- 9
- Citations by year
- 2026: 45 · 2025: 63 · 2024: 43 · 2023: 30 · 2022: 8
- FWCI
- 21.73
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- JAMA Neurology (publishedVersion)
- PubMed (publishedVersion)
- Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Neurology › Intracerebral and Subarachnoid Hemorrhage Research
- Keywords
- amyloid-related imaging abnormalities, anti-amyloid monoclonal antibodies, Alzheimer's disease, aducanumab, ARIA-E, ARIA-H, hemosiderin deposits, microhemorrhages, superficial siderosis, APOE ε4, treatment dose, withholding treatment, corticosteroids
- MeSH terms
- Aged, Alzheimer Disease, Amyloid, Amyloidosis, Female, Humans, Male, Amyloid beta-Peptides, Apolipoprotein E4, Amyloidogenic Proteins
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