Systematic Literature Review Of Amyloid-related Imaging Abnormality-Edema (ARIA-E) Events In Patients With Alzheimer's Disease Receiving Anti-amyloid Therapy
Keywords:
Alzheimer's Disease, Anti-Amyloid Monoclonal Antibodies, Amyloid Related Imaging Abnormality-EdemaAbstract
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by the accumulation of β-amyloid plaques in the brain. Anti-amyloid monoclonal antibodies (AA-mAbs) have been developed as disease-modifying therapies to reduce β-amyloid deposition; however, their use may lead to amyloid-related imaging abnormalities (ARIA), particularly ARIA-edema (ARIA-E). This study aimed to describe the frequency and characteristics of ARIA-E in patients with AD receiving AA-mAb therapy, including patient and treatment characteristics. A systematic literature review (SLR) was conducted on studies that met predefined inclusion and exclusion criteria. Data extracted included the frequency of ARIA-E, AA-mAb type, dose and treatment regimen, treatment duration, apolipoprotein E ε4 (APOE ε4) carrier status, radiologic severity, and the frequency of symptomatic ARIA-E. The review showed that the reported frequency of ARIA-E ranged from 2% to 36% across the included studies. ARIA-E was more frequently reported among APO ε4 carriers than non-carriers. The frequency of ARIA-E varied across AA-mAb types, doses, and treatment regimens, with a tendency toward higher occurrence with greater therapeutic exposure, although this pattern was not consistent across all therapies. Most ARIA-E cases were classified as moderate through radiological scanning, and the majority were asymptomatic and only detected through routine magnetic resonance imaging (MRI) monitoring. These findings indicate that ARIA-E remains an important safety consideration in AA-mAb therapy, particularly in patients with APO ε4 carrier status and greater therapeutic exposure. Regular MRI monitoring is therefore important for early detection and appropriate management of ARIA-E during treatment.
References
A. Gustavsson et al., “Global estimates on the number of persons across the Alzheimer’s disease continuum,” Alzheimer’s Dement., vol. 19, no. 2, pp. 658–670, 2023, doi: 10.1002/alz.12694.
B. H. Kim, S. Kim, Y. Nam, Y. H. Park, S. M. Shin, and M. Moon, “Second-generation anti-amyloid monoclonal antibodies for Alzheimer’s disease: current landscape and future perspectives,” Transl. Neurodegener., vol. 14, no. 1, pp. 1–19, 2025, doi: 10.1186/s40035-025-00465-w.
K. I. Avgerinos, L. Ferrucci, and D. Kapogiannis, “Effects of monoclonal antibodies against amyloid-β on clinical and biomarker outcomes and adverse event risks: A systematic review and meta-analysis of phase III RCTs in Alzheimer’s disease,” Ageing Res. Rev., vol. 68, no. 5, p. 101339, Jul. 2021, doi: 10.1016/j.arr.2021.101339.
R. Vandenberghe et al., “Bapineuzumab for mild to moderate Alzheimer ’ s disease in two global , randomized , phase 3 trials,” Alzheimers. Res. Ther., pp. 1–13, 2016, doi: 10.1186/s13195-016-0189-7.
S. Salloway et al., “TRAILBLAZER-ALZ 4 : A phase 3 trial comparing donanemab with aducanumab on amyloid plaque clearance in early , symptomatic Alzheimer ’ s disease,” no. April, pp. 1–11, 2025, doi: 10.1002/alz.70293.
I. Gueorguieva et al., “Donanemab exposure-response in early symptomatic Alzheimer ’ s disease Kay Chow 1,” no. June, pp. 1–13, 2025, doi: 10.1002/alz.70491.
S. Ostrowitzki et al., “A phase III randomized trial of gantenerumab in prodromal Alzheimer ’ s disease,” pp. 1–15, 2017, doi: 10.1186/s13195-017-0318-y.
C. J. Swanson et al., “proof-of-concept clinical trial in early Alzheimer ’ s disease with lecanemab , an anti-A β protofibril antibody,” vol. 8, pp. 1–14, 2021.
A. Neve, B. Das, J. Wojtowicz, Z. Huang, S. Bullain, and M. Watkin, “Long-Term Safety of Gantenerumab in Participants with Alzheimer ’ s Disease : A Phase III , Double-Blind , and Open-Label Extension Study ( Marguerite RoAD ),” vol. 101, pp. 353–367, 2024, doi: 10.3233/JAD-240221.
H. Arai, H. Yamamoto, Y. Akiba, S. Aiba, and R. Arai, “Amyloid Positron Emission Tomography Imaging at the Onset of Amyloid-Related Abnormalities With Edema in an Alzheimer ’ s Disease Patient Case Presentation,” vol. 17, no. 12, 2025, doi: 10.7759/cureus.100276.
H. Hampel, A. Elhage, M. Cho, L. G. Apostolova, J. A. R. Nicoll, and A. Atri, “Amyloid-related imaging abnormalities ( ARIA ): radiological , biological and clinical characteristics,” Brain, vol. 146, no. 11, pp. 4414–4424, 2023, doi: 10.1093/brain/awad188.
D. Jadhav, N. Saraswat, N. Vyawahare, and D. Shirode, “Targeting the molecular web of Alzheimer’s disease: unveiling pathways for effective pharmacotherapy,” Egypt. J. Neurol. Psychiatry Neurosurg., vol. 60, no. 1, 2024, doi: 10.1186/s41983-023-00775-8.
K. L. Nystuen, S. M. McNamee, M. Akula, K. M. Holton, M. M. DeAngelis, and N. B. Haider, “Alzheimer’s Disease: Models and Molecular Mechanisms Informing Disease and Treatments,” Bioengineering, vol. 11, no. 1, 2024, doi: 10.3390/bioengineering11010045.
H. Wang et al., “Modified titration of donanemab reduces ARIA risk and maintains amyloid reduction,” no. January, pp. 1–11, 2025, doi: 10.1002/alz.70062.
S. Huang, Y. J. Wang, and J. Guo, “Biofluid Biomarkers of Alzheimer’s Disease: Progress, Problems, and Perspectives,” Neurosci. Bull., vol. 38, no. 6, pp. 677–691, 2022, doi: 10.1007/s12264-022-00836-7.
W. Zheng, Y. Zhou, Y. Xia, and Y. Wang, “Association between obstructive sleep apnea severity and glymphatic-related DTI-ALPS alterations in newly diagnosed, Drug-Naïve Alzheimer’s disease,” J. Prev. Alzheimer’s Dis., vol. 13, no. 7, p. 100597, 2026, doi: https://doi.org/10.1016/j.tjpad.2026.100597.
A. Yamazaki et al., “CASE REPORT A case of severe ARIA with multiple infarctions and extensive microbleeds following lecanemab administration,” pp. 1–5, 2025, doi: 10.1111/psyg.13231.
J. N. Hall, “Six Recurrent Amyloid-Related Imaging Abnormality Episodes in aPatient Treated With Aducanumab,” vol. 79, no. 1, pp. 87–89, 2023, doi: 10.1001/jamaneurol.2021.3933.Six.
A. W. Gibson et al., “Ischemic stroke associated with amyloid-related imaging abnormalities in a patient treated with lecanemab,” no. July, pp. 8192–8197, 2024, doi: 10.1002/alz.14223.
Y. Wang et al., “Two cases of Amyloid-Related Imaging Abnormalities ( ARIA ) following lecanemab treatment for alzheimer ’ s disease and a literature review,” 2025., doi: 10.1186/s12883-025-04302-5
Y. Naeshiro, F. Kitani-morii, T. Kasai, and E. Tanaka, “Amyloid Clearance and Transient CSF A β 40 Reduction in a Case of ARIA-E / H Following Lecanemab Treatment,” vol. 40, pp. 1–5, 2025, doi: 10.2169/internalmedicine.6070-25.
