AccScience Publishing / AN / Volume 1 / Issue 1 / DOI: 10.36922/an.v1i1.2
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SPECIAL FEATURE ARTICLE

Insights on amyloid-related imaging abnormalities from the “Pre-Alzheimer’s disease Alliance of China”

Tao-Ran Li1 Ying Han1,2,3,4* on behalf of the Pre-AD Alliance of China5
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1 Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, 100053, China
2 School of Biomedical Engineering, Hainan University, Haikou, 570228, China
3 Center of Alzheimer’s Disease, Beijing Institute for Brain Disorders, Beijing, 100053, China
4 National Clinical Research Center for Geriatric Diseases, Beijing, 100053, China
5 Pre-AD Alliance of China, http://www.alzheimer.org.cn/
Advanced Neurology 2022, 1(1), 2 https://doi.org/10.36922/an.v1i1.2
Submitted: 29 November 2021 | Accepted: 25 February 2022 | Published: 18 March 2022
© 2022 by the Authors. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
Abstract

Alzheimer’s disease (AD) is the most common cause of dementia and accounts for 60 – 80% of all such cases. For approximately 20 years, the research and development of new drugs for AD all ended in failure; however, aducanumab was recently granted accelerated approval by the US Food and Drug Administration. Aducanumab is a representative passive anti-β-amyloid (Aβ) immunotherapy and is the only approved drug that directly targets the pathological changes of AD; it can significantly reduce brain Aβ deposition, which is a hallmark of AD. During the clinical trials of amyloid-targeting monoclonal antibodies, represented by aducanumab, amyloid-related imaging abnormalities (ARIA) were the most common and important adverse reactions. Therefore, before the large-scale clinical application of amyloid-targeting monoclonal antibodies, clinicians and radiologists need to fully understand ARIA so that they can make more informed decisions. Considering the very uneven distribution of medical resources in China, we — on behalf of the “Pre-AD Alliance of China” — believe that it is necessary to write a consensus to elaborate on the mechanisms, risk factors, identification methods, and administration processes of ARIA.

Keywords
Alzheimer’s disease
Amyloid-related imaging abnormalities
Edema
Sulcal effusion
Microhemorrhage
Superficial siderosis
Funding
National Natural Science Foundation of China
References
[1]

Gauthier S, Rosa-Neto P, Morais JA, et al., 2021, World Alzheimer Report 2021: Journey Through the Diagnosis of Dementia. Alzheimer’s Disease International, England.

[2]

Collaborators GD, 2019, Global, regional, and national burden of Alzheimer’s disease and other dementias, 1990- 2016: A systematic analysis for the global burden of disease study 2016. Lancet Neurol, 18(1): 88–106.

[3]

Drew L, 2018, An age-old story of dementia. Nature, 559(7715): S2–S3.

[4]

Wu YT, Beiser AS, Breteler MM, et al., 2017, The changing prevalence and incidence of dementia over time-current evidence. Nat Rev Neurol, 13(6): 327–339.

[5]

Jia L, Du Y, Chu L, et al., 2020, Prevalence, risk factors, and management of dementia and mild cognitive impairment in adults aged 60 years or older in China: A cross-sectional study. Lancet Public Health, 5(12): e661–e671.

[6]

Jia J, Wei C, Chen S, et al., 2018, The cost of Alzheimer’s disease in China and re-estimation of costs worldwide. Alzheimers Dement, 14(4): 483–491.

[7]

Jia L, Quan M, Fu Y, et al., 2020, Dementia in China: Epidemiology, clinical management, and research advances. Lancet Neurol, 19(1): 81–92. http://doi.org/10.1016/S1474-4422(19)30290-X

[8]

Scheltens P, De Strooper B, Kivipelto M, et al., 2021, Alzheimer’s disease. Lancet, 397(10284): 1577–1590. http://doi.org/10.1016/S0140-6736(20)32205-4

[9]

Long JM, Holtzman DM, 2019, Alzheimer disease: An update on pathobiology and treatment strategies. Cell, 179(2): 312–339. http://doi.org/10.1016/j.cell.2019.09.001

[10]

Jan AT, Azam M, Rahman S, et al., 2017, Perspective insights into disease progression, diagnostics, and therapeutic approaches in Alzheimer’s disease: A judicious update. Front Aging Neurosci, 9: 356. http://doi.org/10.3389/fnagi.2017.00356

[11]

Luo J, Agboola F, Grant E, et al., 2020, Sequence of Alzheimer disease biomarker changes in cognitively normal adults: A cross-sectional study. Neurology, 95(23): e3104-e3116. http://doi.org/10.1212/WNL.0000000000010747

[12]

Palmqvist S, Insel PS, Stomrud E, et al., 2019, Cerebrospinal fluid and plasma biomarker trajectories with increasing amyloid deposition in Alzheimer’s disease. EMBO Mol Med, 11(12): e11170.

[13]

Guo T, Korman D, Baker SL, et al., 2021, Longitudinal cognitive and biomarker measurements support a unidirectional pathway in Alzheimer’s disease pathophysiology. Biol Psychiatry, 89(8): 786–794. http://doi.org/10.1016/j.biopsych.2020.06.029

[14]

Jack CJ Jr., Wiste HJ, Therneau TM, et al., 2019, Associations of amyloid, tau, and neurodegeneration biomarker profiles with rates of memory decline among individuals without dementia. JAMA, 321(23): 2316–2325.

[15]

Jack CR Jr., Bennett DA, Blennow K, et al., 2018, NIA-AA research framework: Toward a biological definition of Alzheimer’s disease. Alzheimers Dement, 14(4): 535–562. http://doi.org/10.1016/j.jalz.2018.02.018

[16]

Donohue MC, Sperling RA, Petersen R, et al., 2017, Association between elevated brain amyloid and subsequent cognitive decline among cognitively normal persons. JAMA, 317(22): 2305–2316. http://doi.org/10.1001/jama.2017.6669

[17]

Cummings J, Lee G, Zhong K, et al., 2021, Alzheimer’s disease drug development pipeline: 2021. Alzheimers Dement (NY), 7(1): e12179. http://doi.org/10.1002/trc2.12179

[18]

Cummings J, Aisen P, Lemere C, et al., 2021, Aducanumab produced a clinically meaningful benefit in association with amyloid lowering. Alzheimers Res Ther, 13(1): 98. http://doi.org/10.1186/s13195-021-00838-z

[19]

Salloway S, Sperling R, Gilman S, et al., 2009, A phase 2 multiple ascending dose trial of bapineuzumab in mild to moderate Alzheimer disease. Neurology, 73(24): 2061– 2070.

[20]

Jeremic D, Jiménez-Díaz L, Navarro-López JD, 2021, Past, present and future of therapeutic strategies against amyloid- beta peptides in Alzheimer’s disease: A systematic review. Ageing Res Rev, 72: 101496. http://doi.org/10.1016/j.arr.2021.101496

[21]

DiFrancesco JC, Longoni M, Piazza F, 2015, Anti-abeta autoantibodies in amyloid related imaging abnormalities (ARIA): Candidate biomarker for immunotherapy in Alzheimer’s disease and cerebral amyloid angiopathy. Front Neurol, 6: 207. http://doi.org/10.3389/fneur.2015.00207

[22]

Sperling RA, Jack CR Jr., Black SE, et al., 2011, Amyloid- related imaging abnormalities in amyloid-modifying therapeutic trials: Recommendations from the Alzheimer’s association research roundtable workgroup. Alzheimers Dement, 7(4): 367–385. http://doi.org/10.1016/j.jalz.2011.05.2351

[23]

Barakos J, Sperling R, Salloway S, et al., 2013, MR imaging features of amyloid-related imaging abnormalities. AJNR Am J Neuroradiol, 34(10): 1958–1965.

[24]

Cummings J, Aisen P, Apostolova LG, et al., 2021, Aducanumab: Appropriate use recommendations. J Prev Alzheimers Dis, 8(4): 398–410.

[25]

Haeberlein SB, von Hehn C, Tian Y, et al., 2019, EMERGE and ENGAGE Topline Results: Two Phase 3 Studies to Evaluate Aducanumab in Patients With Early Alzheimer’s Disease. Available from: https://investors.biogen.com/ static-files/f91e95d9-2fce-46ce-9115-0628cfe96e83 [Last accessed on 2022 Mar 16].

[26]

Sperling R, Salloway S, Brooks DJ, et al., 2012, Amyloid-related imaging abnormalities in patients with Alzheimer’s disease treated with bapineuzumab: A retrospective analysis. Lancet Neurol, 11(3): 241–249. http://doi.org/10.1016/S1474-4422(12)70015-7

[27]

Carlson C, Estergard W, Oh J, et al., 2011, Prevalence of asymptomatic vasogenic edema in pretreatment Alzheimer’s disease study cohorts from phase 3 trials of semagacestat and solanezumab. Alzheimers Dement, 7(4): 396–401. http://doi.org/10.1016/j.jalz.2011.05.2353

[28]

Pichler M, Vemuri P, Rabinstein AA, et al., 2017, Prevalence and natural history of superficial siderosis: A population based study. Stroke, 48(12): 3210–3214. http://doi.org/10.1161/STROKEAHA.117.018974

[29]

Vernooij MW, van der Lugt A, Ikram MA, et al., 2008, Prevalence and risk factors of cerebral microbleeds: The Rotterdam scan study. Neurology, 70(14): 1208–1214. http://doi.org/10.1212/01.wnl.0000307750.41970.d9

[30]

Gutt S, Brocco A, Sharma S, 2019, Variability of Aria Detection in Patients Receiving Monoclonal Antibodies Against Amyloid-β PLAQUES, Poster Presented at AAIC 2019 (P1-045).

[31]

Avgerinos KI, Ferrucci L, Kapogiannis D, 2021, Effects of monoclonal antibodies against amyloid-beta 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, 68: 101339. http://doi.org/10.1016/j.arr.2021.101339

[32]

Ketter N, Brashear HR, Bogert J, et al., 2017, Central review of amyloid-related imaging abnormalities in two Phase III clinical trials of bapineuzumab in mild-to-moderate Alzheimer’s disease patients. J Alzheimers Dis, 57(2): 557–573. http://doi.org/10.3233/JAD-160216

[33]

Brashear HR, Ketter N, Bogert J, et al., 2018, Clinical evaluation of amyloid-related imaging abnormalities in bapineuzumab phase III studies. J Alzheimers Dis, 66(4): 1409–1424. http://doi.org/10.3233/JAD-180675

[34]

Ostrowitzki S, Lasser RA, Dorflinger E, et al., 2017, A phase III randomized trial of gantenerumab in prodromal Alzheimer’s disease. Alzheimers Res Ther, 9(1): 95. http://doi.org/10.1186/s13195-017-0318-y

[35]

Swanson CJ, Zhang Y, Dhadda S, et al., 2021, A randomized, double-blind, phase 2b proof-of-concept clinical trial in early Alzheimer’s disease with lecanemab, an anti-Abeta protofibril antibody. Alzheimers Res Ther, 13(1): 80. http://doi.org/10.1186/s13195-021-00813-8

[36]

Arrighi HM, Barakos J, Barkhof F, et al., 2016, Amyloid- related imaging abnormalities-haemosiderin (ARIA-H) in patients with Alzheimer’s disease treated with bapineuzumab: A historical, prospective secondary analysis. J Neurol Neurosurg Psychiatry, 87(1): 106–112. http://doi.org/10.1136/jnnp-2014-309493

[37]

Chalkias S, Umans K, Castrillo-Viguera C, et al., 2021, Considerations for the Real-World Management of ARIA From the Aducanumab Phase 3 Studies EMERGE and ENGAGE. AAIC 2021 Poster 57498.

[38]

Liu E, Wang D, Sperling R, et al., 2018, Biomarker Pattern of ARIA-E Participants in Phase 3 Randomized Clinical Trials with Bapineuzumab. Neurology, 90(10): e877–e886.

[39]

Budd HS, O’Gorman J, Chiao P, et al., 2017, Clinical development of aducanumab, an anti-abeta human monoclonal antibody being investigated for the treatment of early Alzheimer’s disease. J Prev Alzheimers Dis, 4(4): 255–263. http://doi.org/10.14283/jpad.2017.39

[40]

Salloway S, Sperling R, Fox NC, et al., 2014, Two phase 3 trials of bapineuzumab in mild-to-moderate Alzheimer’s disease. N Engl J Med, 370(4): 322–333. http://doi.org/10.1056/NEJMoa1304839

[41]

Zago W, Schroeter S, Guido T, et al., 2013, Vascular alterations in PDAPP mice after anti-Abeta immunotherapy: Implications for amyloid-related imaging abnormalities. Alzheimers Dement, 9 Suppl 5: S105–S115. http://doi.org/10.1016/j.jalz.2012.11.010 

[42]

Greenberg SM, Bacskai BJ, Hernandez-Guillamon M, et al., 2020, Cerebral amyloid angiopathy and Alzheimer disease- one peptide, two pathways. Nat Rev Neurol, 16(1): 30–42. http://doi.org/10.1038/s41582-019-0281-2

[43]

Caselli RJ, Walker D, Sue L, et al., 2010, Amyloid load in nondemented brains correlates with APOE e4. Neurosci Lett., 473(3): 168–171. http://doi.org/10.1016/j.neulet.2010.02.016

[44]

Harrison CH, Sakai K, Johnston DA et al., 2019, The Role of Capillary Angiopathy and Aquaporin 4 in Aria Induced by Aβ Immunization, Oral Presentation at AAIC 2019 (O3- 10-03).

[45]

Blockx I, Einstein S, Guns PJ, et al., 2016, Monitoring blood-brain barrier integrity following amyloid-beta immunotherapy using gadolinium-enhanced MRI in a PDAPP mouse model. J Alzheimers Dis, 54(2): 723–735. http://doi.org/10.3233/JAD-160023 

[46]

Eng JA, Frosch MP, Choi K, et al., 2004, Clinical manifestations of cerebral amyloid angiopathy-related inflammation. Ann Neurol, 55(2): 250–256. http://doi.org/10.1002/ana.10810

[47]

Kinnecom C, Lev MH, Wendell L, et al., 2007, Course of cerebral amyloid angiopathy-related inflammation. Neurology, 68(17): 1411–1416. http://doi.org/10.1212/01.wnl.0000260066.98681.2e

[48]

Piazza F, Greenberg SM, Savoiardo M, et al., 2013, Anti- amyloid beta autoantibodies in cerebral amyloid angiopathy- related inflammation: Implications for amyloid-modifying therapies. Ann Neurol, 73(4): 449–458. http://doi.org/10.1002/ana.23857

[49]

Administration, US, FDA. Drugs@FDA: FDA Approved Drugs. Aducanumab; 2021. Available from: https://www. fda.gov/drugs/news-events-human-drugs/fdas-decision-approve-new-treatment-alzheimers-disease [Last accessed on 2022 Mar 16].

[50]

Mullard A, 2021, Landmark Alzheimer’s drug approval confounds research community. Nature, 594(7863): 309–310. http://doi.org/10.1038/d41586-021-01546-2 

[51]

Steinbrook R, 2021, The accelerated approval of aducanumab for treatment of patients with Alzheimer disease. JAMA Intern Med, 181(10): 1281. http://doi.org/10.1001/jamainternmed.2021.4622

[52]

Planche V, Villain N, 2021, US food and drug administration approval of aducanumab-is amyloid load a valid surrogate end point for Alzheimer disease clinical trials? JAMA Neurol, 78(11): 1307–1308. http://doi.org/10.1001/jamaneurol.2021.3126

Conflict of interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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Advanced Neurology, Electronic ISSN: 2810-9619 Published by AccScience Publishing