Multiple Ischemic Strokes in a Patient Treated with Lecanemab: A Case Report

Multiple Ischemic Strokes in a Patient Treated with Lecanemab: A Case Report | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Multiple Ischemic Strokes in a Patient Treated with Lecanemab: A Case Report Hajar Alammar, Daniel A Llano This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5845699/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Amyloid-lowering therapy has been previously associated with the formation of cerebral edema and/or microhemorrhage, often picked up on MRI and referred to as amyloid-related imaging abnormalities, or ARIA. Case presentation: We describe a case of a patient with Alzheimer’s Disease treated with the amyloid-lowering drug lecanemab who developed both ARIA-H and ARIA-E, and multiple ischemic infarctions. Conclusion This finding, in conjunction with previous reports of ischemic infarction in the setting of anti-amyloid therapy, suggests that amyloid-lowering therapy may predispose individuals to both hemorrhagic and ischemic infarction. This result is discussed in the context of microvascular pathology known to occur in the setting of Alzheimer’s Disease. Alzheimer’s Disease Lecanemab ischemic stroke Figures Figure 1 Figure 2 Background Anti-amyloid therapies, including lecanemab, are newly emergent treatments for Alzheimer's Disease (AD) that focus on the removal of amyloid β from the brain. AD has a complex pathophysiology characterized by synaptic dysregulation and the presence of amyloid β-containing plaques and tau-containing neurofibrillary tangles [1]. Amyloid Aβ peptide is formed by cleavage of amyloid precursor protein (APP), a transmembrane protein in neuronal synapses, by β secretase and γ secretase [1, 2]. It is then secreted as Aβ monomers into the extracellular space, which has a predilection for aggregation, forming soluble oligomers, fibrils, and then into plaques [1, 3]. Aβ clearance is modulated in part through apolipoprotein E (ApoE), which is encoded by the ApoE gene [4, 5]. ApoE has polymorphisms with three different alleles encoding three isoforms: E2, E3, and E4. The presence of the ApoE4 allele is associated with a gene dose-dependent AD risk and earlier onset, and the presence of ApoE4 was found to be associated with slower clearance of Aβ and, therefore, earlier and higher Aβ accumulation followed by ApoE3 and then ApoE2 [4, 5]. Lecanemab is a humanized monoclonal antibody that targets Aβ soluble aggregates [6]. Phase 3 clinical trials of the use of lecanemab in mild cognitive impairment and early AD showed a modest diminishment of cognitive and functional decline over 18 months compared to placebo; however, with risk of adverse events, including amyloid-related imaging abnormalities (ARIA) [7]. ARIA has been described in patients with AD who have been treated with anti-amyloid therapy in two forms: either ARIA-E when edema and sulcal effacement develop or ARIA-H when hemorrhage or superficial siderosis develops [8]. Subjects treated with lecanemab showed an incidence of ARIA-H in 17.3% and ARIA-E in 12.6% of patients, with a higher incidence in ApoE4 carrier patients, especially homozygous ones [7]. ARIA can be symptomatic or asymptomatic and can be classified based on MRI into mild, moderate, or severe depending on the number and size of different lesions [8]. Ischemic cerebrovascular disease has also been associated with AD. Microvascular pathology frequency coexists with AD pathology in autopsy series and has been etiologically linked to the development of AD [9–11], reviewed in [12]. Microvascular pathology is also seen early in the course of AD in an animal model and has been found to be one of the earliest changes seen in AD biomarkers [13, 14]. Thus, AD patients may be predisposed to ischemic microvascular disease, but it is not known if the rapid removal of amyloid β predisposes to ischemic microvascular disease. A previous case report [15] has suggested that treatment with lecanemab may lead to ischemic stroke. Here, we provide an additional case report demonstrating ischemic changes after initiating lecanemab. Case presentation A 76-year-old female with a past medical history of low-grade transitional cell carcinoma treated with transurethral resection of bladder tumor seven years prior to presentation and monitored through yearly cystoscopy, osteoporosis, and AD was referred to the emergency department for magnetic resonance imaging (MRI) findings of bilateral cerebellar acute infarctions seen on routine lecanemab monitoring MRI scan. She was diagnosed with amnestic mild cognitive impairment six years prior to the current presentation, and she was started on memantine 5 mg twice daily for this. Three years later, she had an MRI that showed a small venous angioma in the right frontal lobe, mild cortical atrophy, moderate white matter small vessel ischemic changes, and an incidental left posterior parietal encephalomalacia. Her Montreal Cognitive Assessment (MoCA) score at the time was 22/30. Donepezil was added, but she did not tolerate it due to diarrhea and was switched to a rivastigmine patch. Two years later, she stopped driving due to difficulty with maneuvering in a parking and getting lost in familiar locations along with the progression of memory impairment and some paranoia. The patient and family expressed interest in lecanemab. Amyloid positron emission tomography (amyloid PET) scan confirmed the presence of brain amyloidosis, showing moderate to frequent beta-amyloid neuritic plaques. The patient scored 7/30 on the Functional Activities Questionnaire (FAQ), and genetic testing showed ApoE showed E2 and E3 isoforms. A repeat MRI showed stable prior findings, and the patient was started on intravenous infusions of lecanemab every 2 weeks. She tolerated them well and had a repeat MRI after her fourth infusion. The MRI showed a 7 mm area of hemosiderin deposition in the right frontal lobe, new since starting lecanemab infusions, consistent with mild ARIA-H. After the sixth infusion a surveillance MRI revealed several small Diffusion Weighted Imaging (DWI) bright lesions in the bilateral cerebellum (Fig. 1 ) as well as sulcal effusions in the left occipital lobe consistent with new mild ARIA-E (Fig. 2 ). She was sent to the emergency department based on these findings. The patient and her husband, who is the primary caregiver, denied any symptoms, such as unsteadiness, spinning sensation, weakness, or visual or sensory changes. She walks without assistance. Her husband noted that since the start of the infusion, her memory has slightly worsened and that she started experiencing agitation at night. She was alert and oriented to person and place as a hospital but not the hospital's or city's name. She knew the month but not the day or year. She did not know who the current president was; her language was fluent, and she had good comprehension. She was not able to recite the days of the week backward. The remainder of her neurological physical examination, including cerebellar examination, was intact. She underwent a stroke workup with an electrocardiogram (ECG), which showed a normal sinus rhythm, a glycated hemoglobin (A1C) of 5.6%, and a 74 mg/dL LDL cholesterol. She underwent magnetic resonance angiography (MRA) of the head and neck without contrast, which showed no large vessel occlusion or hemodynamically significant narrowing. The echocardiogram was unremarkable, aside from a borderline enlarged left atrium. She was discharged on 81 mg aspirin, atorvastatin 40 mg, and a 30-day cardiac events monitor. Electroencephalogram (EEG) showed diffuse background slowing with no epileptiform discharges, indicating mild to moderate encephalopathy. Lecanemab was stopped. Discussion Here, we present a patient without known typical stroke risk factors who presents with several ischemic strokes 10 weeks after starting intravenous infusions of lecanemab. It is possible that these strokes are incidental and unrelated to the initiation of lecanemab, particularly since there is evidence of previous encephalomalacia on a previous MRI scan. However, the presence of the previous encephalomalacia may have indicated a predilection to cryptogenic stroke that may have manifested after the initiation of lecanemab. The mechanism by which amyloid removal may lead to stroke is not known, but it is possible that the inflammatory response generated in the setting of amyloid removal [16, 17] may have led to microvascular occlusion. It is also possible that the oncotic load, inflammatory response, or other mechanisms led to embolism originating from a central source and traveling to the cerebellum. Only one prior study that we are aware of has reported ischemic stroke in lecanemab-treated patients [15], although a previous case report also indicates ischemic stroke in a patient receiving an earlier generation drug, bapineuzumab [18]. In the lecanemab case, a 71-year-old male who is heterozygous with ApoE3 and ApoE4 presented with bifrontal headache a few days after his third infusion of lecanemab, and the MRI was consistent with severe ARIA-E and mild ARIA-H and a small ischemic stroke in the right occipital lobe. He had continuous EEG that revealed three focal electrographic seizures with no clinical accompaniments. After two weeks, his repeated MRI showed another new punctate stroke in the same area. The patient's stroke workup was negative, and the impression was that it was secondary to ongoing ARIA-E-related inflammation. She was treated with steroids. ARIA's pathophysiology is hypothesized to be stimulated by anti-amyloid therapy, which mobilize Aβ into the vasculature and increase its deposition in perivascular spaces, thereby disrupting vascular stability and leading to blood leakage and edema and, or hemorrhages, which is similar to CAA and cerebral amyloid angiopathy-related inflammation (CCAri) [19, 20]. CCAri was found to be associated with T-cell infiltration, microglial activation, and anti-amyloid autoantibody production [21, 22]. In more severe cases, it can develop into Aβ-related angiitis with lymphocytic infiltration and granulomatous changes [23]. Just as CAA predisposes to both ischemic and hemorrhagic stroke [24], both patients described above that received lecanemab had both ischemic and hemorrhagic complications seen after starting lecanemab. These reports serve as points of caution for the initiation of lecanemab in elderly patients, particularly if there is evidence of previous ischemic stroke on imaging. Aggressive workup of stroke risk factors prior to initiating lecanemab or similar antibodies may be warranted. If anti-amyloid therapy does predispose to ischemic stroke, this could pose a significant problem, given the concerns around thrombolysis or dual antiplatelet therapy in patients that have also had ARIA [25]. Therefore, future work should continue to prospectively assess ischemic stroke risk after initiating anti-amyloid therapy. Abbreviations Alzheimer's Disease (AD), amyloid precursor protein (APP), apolipoprotein E (ApoE), amyloid-related imaging abnormalities (ARIA) Montreal Cognitive Assessment (MoCA), Functional Activities Questionnaire (FAQ), Amyloid positron emission tomography (amyloid PET), Diffusion Weighted Imaging (DWI), electrocardiogram (ECG), magnetic resonance angiography (MRA), Electroencephalogram (EEG), cerebral amyloid angiopathy-related inflammation (CCAri). Declarations Ethics Approval, Consent to Participate and Consent to Publish : This case report was conducted in accordance with ethical standards. Consent for publication was obtained from the patient and her husband. Availability of Data and Materials : The data supporting the findings of this case report are available upon request from the corresponding author. Competing Interests : D.A.L has previously received consulting fees from Eisai Pharmaceuticals. All other authors declare no competing interests. Funding : No funding was received for the preparation or publication of this manuscript. Authors' Contributions : H.A. was responsible for the conceptualization and design of the case report, patient assessment, data collection (including medical history, clinical examination, and diagnostic tests), and drafting the initial manuscript. D.A.L. provided clinical oversight, managed the case, and contributed to the interpretation of medical data and critical revision of the manuscript for intellectual content and clinical accuracy. Both authors have approved the final version of the manuscript and are accountable for all aspects of the work. Acknowledgements : None. References Knopman, D., H. Amieva, R. Petersen, G. Chételat, D. Holtzman, B. Hyman, R. Nixon and D. Jones, Alzheimer Disease Nat Rev Dis Primers 7: 33 . 2021. Thinakaran, G. and E.H. Koo (2008) Amyloid precursor protein trafficking, processing, and function. Journal of Biological Chemistry . 283 (44): p. 29615–29619 Spires-Jones, T.L. and B.T. Hyman (2014) The intersection of amyloid beta and tau at synapses in Alzheimer’s disease. Neuron . 82 (4): p. 756–771 Kim, J., J.M. Basak and D.M. Holtzman (2009) The role of apolipoprotein E in Alzheimer's disease. Neuron . 63 (3): p. 287–303 Huynh, T.-P.V., A.A. Davis, J.D. Ulrich and D.M. Holtzman (2017) Apolipoprotein E and Alzheimer's disease: the influence of apolipoprotein E on amyloid-β and other amyloidogenic proteins: Thematic Review Series: ApoE and Lipid Homeostasis in Alzheimer's Disease. Journal of lipid research . 58 (5): p. 824–836 Tucker, S., C. Möller, K. Tegerstedt, A. Lord, H. Laudon, J. Sjödahl, L. Söderberg, E. Spens, C. Sahlin and E.R. Waara (2015) The murine version of BAN2401 (mAb158) selectively reduces amyloid-β protofibrils in brain and cerebrospinal fluid of tg-ArcSwe mice. Journal of Alzheimer's Disease . 43 (2): p. 575–588 Van Dyck, C.H., C.J. Swanson, P. Aisen, R.J. Bateman, C. Chen, M. Gee, M. Kanekiyo, D. Li, L. Reyderman and S. Cohen (2023) Lecanemab in early Alzheimer’s disease. New England Journal of Medicine . 388 (1): p. 9–21 Vukmir, R.B. (2024) Amyloid-related imaging abnormalities (ARIA): diagnosis, management, and care in the setting of amyloid‐modifying therapy. Annals of clinical and translational neurology . 11 (7): p. 1669–1680 Toledo, J.B., S.E. Arnold, K. Raible, J. Brettschneider, S.X. Xie, M. Grossman, S.E. Monsell, W.A. Kukull and J.Q. Trojanowski (2013) Contribution of cerebrovascular disease in autopsy confirmed neurodegenerative disease cases in the National Alzheimer’s Coordinating Centre. Brain . 136 (9): p. 2697–2706 Van Groen, T., K. Puurunen, H.-M. Mäki, J. Sivenius and J. Jolkkonen (2005) Transformation of diffuse β-amyloid precursor protein and β-amyloid deposits to plaques in the thalamus after transient occlusion of the middle cerebral artery in rats. Stroke . 36 (7): p. 1551–1556 Garcia-Alloza, M., J. Gregory, K.V. Kuchibhotla, S. Fine, Y. Wei, C. Ayata, M.P. Frosch, S.M. Greenberg and B.J. Bacskai (2011) Cerebrovascular lesions induce transient β-amyloid deposition. Brain . 134 (12): p. 3697–3707 Marchesi, V.T. (2011) Alzheimer's dementia begins as a disease of small blood vessels, damaged by oxidative-induced inflammation and dysregulated amyloid metabolism: implications for early detection and therapy. The FASEB Journal . 25 (1): p. 5–13 Iturria-Medina, Y., R.C. Sotero, P.J. Toussaint, J.M. Mateos-Pérez and A.C. Evans (2016) Early role of vascular dysregulation on late-onset Alzheimer’s disease based on multifactorial data-driven analysis. Nature communications . 7 (1): p. 11934 Lowerison, M.R., N.V.C. Sekaran, Z. Dong, X. Chen, Q. You, D.A. Llano and P. Song (2024) Super-resolution ultrasound reveals cerebrovascular impairment in a mouse model of Alzheimer's Disease. Journal of Neuroscience . 44 (9) Gibson, A.W., H. Elser, M. Rosso, E.J. Cornblath, Y. Fonkeu, S. Prasad, A. Rothstein, I.M. Nasrallah, D.A. Wolk and M.H. Guo (2024) Ischemic stroke associated with amyloid-related imaging abnormalities in a patient treated with lecanemab. Alzheimer's & Dementia . 20 (11): p. 8192–8197 Solopova, E., W. Romero-Fernandez, H. Harmsen, L. Ventura-Antunes, E. Wang, A. Shostak, J. Maldonado, M.J. Donahue, D. Schultz and T.M. Coyne (2023) Fatal iatrogenic cerebral β-amyloid-related arteritis in a woman treated with lecanemab for Alzheimer’s disease. Nature communications . 14 (1): p. 8220 Castellani, R.J., E.D. Shanes, M. McCord, N.J. Reish, M.E. Flanagan, M.M. Mesulam and P. Jamshidi (2023) Neuropathology of Anti-Amyloid-β Immunotherapy: A Case Report. J Alzheimers Dis . 93 (2): p. 803–813 Roher, A.E., C.L. Maarouf, I.D. Daugs, T.A. Kokjohn, J.M. Hunter, M.N. Sabbagh and T.G. Beach (2011) Neuropathology and amyloid-β spectrum in a bapineuzumab immunotherapy recipient. J Alzheimers Dis . 24 (2): p. 315 − 25.PMC3172868 Kozberg, M.G., I. Yi, W.M. Freeze, C.A. Auger, A.A. Scherlek, S.M. Greenberg and S.J. van Veluw (2022) Blood–brain barrier leakage and perivascular inflammation in cerebral amyloid angiopathy. Brain Communications . 4 (5): p. fcac245 Bilodeau, P.A., J.R. Dickson and M.G. Kozberg (2024) The Impact of Anti-Amyloid Immunotherapies on Stroke Care. Journal of Clinical Medicine . 13 (5): p. 1245 Piazza, F., S.M. Greenberg, M. Savoiardo, M. Gardinetti, L. Chiapparini, I. Raicher, R. Nitrini, H. Sakaguchi, M. Brioschi and G. Billo (2013) Anti–amyloid β autoantibodies in cerebral amyloid angiopathy–related inflammation: implications for amyloid-modifying therapies. Annals of neurology . 73 (4): p. 449–458 Kinnecom, C., M. Lev, L. Wendell, E. Smith, J. Rosand, M. Frosch and S. Greenberg (2007) Course of cerebral amyloid angiopathy–related inflammation. Neurology . 68 (17): p. 1411–1416 Scolding, N.J., F. Joseph, P.A. Kirby, I. Mazanti, F. Gray, J. Mikol, D. Ellison, D.A. Hilton, T.L. Williams and J.M. MacKenzie (2005) Aβ-related angiitis: primary angiitis of the central nervous system associated with cerebral amyloid angiopathy. Brain . 128 (3): p. 500–515 Xiong, L., S.J. Van Veluw, N. Bounemia, A. Charidimou, M. Pasi, G. Boulouis, Y.D. Reijmer, A.-K. Giese, S. Davidsdottir and P. Fotiadis (2018) Cerebral cortical microinfarcts on magnetic resonance imaging and their association with cognition in cerebral amyloid angiopathy. Stroke . 49 (10): p. 2330–2336 Greenberg, S.M., H.J. Aparicio, K.L. Furie, M.S. Goyal, J.D. Hinman, M. Kozberg, A. Leonard, M.J. Fisher, A.H.A.S. Council, C.o. Cardiovascular, S. Nursing, and C.o.C. Cardiology (2024) Vascular Neurology Considerations for Antiamyloid Immunotherapy: A Science Advisory From the American Heart Association. Stroke , Additional Declarations Competing interest reported. D.A.L has previously received consulting fees from Eisai Pharmaceuticals Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5845699","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":407330234,"identity":"a632a9e8-281d-472b-827c-c8fc684fd257","order_by":0,"name":"Hajar Alammar","email":"","orcid":"","institution":"Carle Foundation Hospital","correspondingAuthor":false,"prefix":"","firstName":"Hajar","middleName":"","lastName":"Alammar","suffix":""},{"id":407330235,"identity":"450eeaf9-9c60-4e4f-83fe-76901595f0a3","order_by":1,"name":"Daniel A Llano","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA6klEQVRIiWNgGAWjYDCCAyBUwCDDB+J8AGI+4rQYMPCwAdmMM4AEGzFaGGBamHmI0cJ3/OzBAx9AWtjPHnxsU2OXz8bewPjhYw5uLZJn8hIOzgBp4clLNs45lmzZxnOAWXLmNtxaDA7kGBzmATssx0w6t4HZgE0igY2ZF5+W828MDv8BaeF/YyZt2VBvwCb/gICWG0BbwN6XANrC2HAYaAsDfi2SN94YHOwxkABqeWNs2HPsuAEbT2IzXr/wnc8x/vCjwkaOnz/H8MGPmmoDfvbDBz98xKMFCiSQOYwNBNWPglEwCkbBKMAPAM1hRUUADmirAAAAAElFTkSuQmCC","orcid":"","institution":"Carle Foundation Hospital","correspondingAuthor":true,"prefix":"","firstName":"Daniel","middleName":"A","lastName":"Llano","suffix":""}],"badges":[],"createdAt":"2025-01-17 03:38:10","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5845699/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5845699/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":74944567,"identity":"f819e77a-1a62-46ca-acd8-26b41b2b5996","added_by":"auto","created_at":"2025-01-28 15:19:14","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":2033764,"visible":true,"origin":"","legend":"\u003cp\u003eThree different axial sections showing diffusion-weighted images (left) and apparent diffusion coefficient images (right) of the cerebellum infarctions in this patient. Arrows show areas of restricted diffusion.\u003c/p\u003e","description":"","filename":"Figure13.png","url":"https://assets-eu.researchsquare.com/files/rs-5845699/v1/49db32306b7841a2de0ac44d.png"},{"id":74944572,"identity":"b378dc79-3a2a-4d3c-9ee4-dff669f9bc2f","added_by":"auto","created_at":"2025-01-28 15:19:14","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":3555172,"visible":true,"origin":"","legend":"\u003cp\u003eTwo different axial fluid attenuated inversion recovery (FLAIR) images demonstrating areas of ARIA-E, taken at the same time as the images in Figure 1.\u003c/p\u003e","description":"","filename":"Figure23.png","url":"https://assets-eu.researchsquare.com/files/rs-5845699/v1/8fb62a2cfff10025726969a7.png"},{"id":76463760,"identity":"9d1b6649-a5ae-4445-a5c9-0a26175bbaee","added_by":"auto","created_at":"2025-02-17 12:01:58","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":4803869,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5845699/v1/9cd0f7b5-20fd-4310-955f-cc5901a549e0.pdf"}],"financialInterests":"Competing interest reported. D.A.L has previously received consulting fees from Eisai Pharmaceuticals","formattedTitle":"Multiple Ischemic Strokes in a Patient Treated with Lecanemab: A Case Report","fulltext":[{"header":"Background","content":" \u003cp\u003eAnti-amyloid therapies, including lecanemab, are newly emergent treatments for Alzheimer's Disease (AD) that focus on the removal of amyloid β from the brain. AD has a complex pathophysiology characterized by synaptic dysregulation and the presence of amyloid β-containing plaques and tau-containing neurofibrillary tangles [1]. Amyloid Aβ peptide is formed by cleavage of amyloid precursor protein (APP), a transmembrane protein in neuronal synapses, by β secretase and γ secretase [1, 2]. It is then secreted as Aβ monomers into the extracellular space, which has a predilection for aggregation, forming soluble oligomers, fibrils, and then into plaques [1, 3]. Aβ clearance is modulated in part through apolipoprotein E (ApoE), which is encoded by the ApoE gene [4, 5]. ApoE has polymorphisms with three different alleles encoding three isoforms: E2, E3, and E4. The presence of the ApoE4 allele is associated with a gene dose-dependent AD risk and earlier onset, and the presence of ApoE4 was found to be associated with slower clearance of Aβ and, therefore, earlier and higher Aβ accumulation followed by ApoE3 and then ApoE2 [4, 5].\u003c/p\u003e \u003cp\u003eLecanemab is a humanized monoclonal antibody that targets Aβ soluble aggregates [6]. Phase 3 clinical trials of the use of lecanemab in mild cognitive impairment and early AD showed a modest diminishment of cognitive and functional decline over 18 months compared to placebo; however, with risk of adverse events, including amyloid-related imaging abnormalities (ARIA) [7]. ARIA has been described in patients with AD who have been treated with anti-amyloid therapy in two forms: either ARIA-E when edema and sulcal effacement develop or ARIA-H when hemorrhage or superficial siderosis develops [8]. Subjects treated with lecanemab showed an incidence of ARIA-H in 17.3% and ARIA-E in 12.6% of patients, with a higher incidence in ApoE4 carrier patients, especially homozygous ones [7]. ARIA can be symptomatic or asymptomatic and can be classified based on MRI into mild, moderate, or severe depending on the number and size of different lesions [8].\u003c/p\u003e \u003cp\u003eIschemic cerebrovascular disease has also been associated with AD. Microvascular pathology frequency coexists with AD pathology in autopsy series and has been etiologically linked to the development of AD [9\u0026ndash;11], reviewed in [12]. Microvascular pathology is also seen early in the course of AD in an animal model and has been found to be one of the earliest changes seen in AD biomarkers [13, 14]. Thus, AD patients may be predisposed to ischemic microvascular disease, but it is not known if the rapid removal of amyloid β predisposes to ischemic microvascular disease. A previous case report [15] has suggested that treatment with lecanemab may lead to ischemic stroke. Here, we provide an additional case report demonstrating ischemic changes after initiating lecanemab.\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cp\u003eA 76-year-old female with a past medical history of low-grade transitional cell carcinoma treated with transurethral resection of bladder tumor seven years prior to presentation and monitored through yearly cystoscopy, osteoporosis, and AD was referred to the emergency department for magnetic resonance imaging (MRI) findings of bilateral cerebellar acute infarctions seen on routine lecanemab monitoring MRI scan. She was diagnosed with amnestic mild cognitive impairment six years prior to the current presentation, and she was started on memantine 5 mg twice daily for this. Three years later, she had an MRI that showed a small venous angioma in the right frontal lobe, mild cortical atrophy, moderate white matter small vessel ischemic changes, and an incidental left posterior parietal encephalomalacia. Her Montreal Cognitive Assessment (MoCA) score at the time was 22/30. Donepezil was added, but she did not tolerate it due to diarrhea and was switched to a rivastigmine patch. Two years later, she stopped driving due to difficulty with maneuvering in a parking and getting lost in familiar locations along with the progression of memory impairment and some paranoia. The patient and family expressed interest in lecanemab.\u003c/p\u003e \u003cp\u003eAmyloid positron emission tomography (amyloid PET) scan confirmed the presence of brain amyloidosis, showing moderate to frequent beta-amyloid neuritic plaques. The patient scored 7/30 on the Functional Activities Questionnaire (FAQ), and genetic testing showed ApoE showed E2 and E3 isoforms. A repeat MRI showed stable prior findings, and the patient was started on intravenous infusions of lecanemab every 2 weeks. She tolerated them well and had a repeat MRI after her fourth infusion. The MRI showed a 7 mm area of hemosiderin deposition in the right frontal lobe, new since starting lecanemab infusions, consistent with mild ARIA-H. After the sixth infusion a surveillance MRI revealed several small Diffusion Weighted Imaging (DWI) bright lesions in the bilateral cerebellum (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) as well as sulcal effusions in the left occipital lobe consistent with new mild ARIA-E (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). She was sent to the emergency department based on these findings.\u003c/p\u003e \u003cp\u003eThe patient and her husband, who is the primary caregiver, denied any symptoms, such as unsteadiness, spinning sensation, weakness, or visual or sensory changes. She walks without assistance. Her husband noted that since the start of the infusion, her memory has slightly worsened and that she started experiencing agitation at night. She was alert and oriented to person and place as a hospital but not the hospital's or city's name. She knew the month but not the day or year. She did not know who the current president was; her language was fluent, and she had good comprehension. She was not able to recite the days of the week backward. The remainder of her neurological physical examination, including cerebellar examination, was intact.\u003c/p\u003e \u003cp\u003eShe underwent a stroke workup with an electrocardiogram (ECG), which showed a normal sinus rhythm, a glycated hemoglobin (A1C) of 5.6%, and a 74 mg/dL LDL cholesterol. She underwent magnetic resonance angiography (MRA) of the head and neck without contrast, which showed no large vessel occlusion or hemodynamically significant narrowing. The echocardiogram was unremarkable, aside from a borderline enlarged left atrium. She was discharged on 81 mg aspirin, atorvastatin 40 mg, and a 30-day cardiac events monitor. Electroencephalogram (EEG) showed diffuse background slowing with no epileptiform discharges, indicating mild to moderate encephalopathy. Lecanemab was stopped.\u003c/p\u003e "},{"header":"Discussion","content":"\u003cp\u003eHere, we present a patient without known typical stroke risk factors who presents with several ischemic strokes 10 weeks after starting intravenous infusions of lecanemab. It is possible that these strokes are incidental and unrelated to the initiation of lecanemab, particularly since there is evidence of previous encephalomalacia on a previous MRI scan. However, the presence of the previous encephalomalacia may have indicated a predilection to cryptogenic stroke that may have manifested after the initiation of lecanemab. The mechanism by which amyloid removal may lead to stroke is not known, but it is possible that the inflammatory response generated in the setting of amyloid removal [16, 17] may have led to microvascular occlusion. It is also possible that the oncotic load, inflammatory response, or other mechanisms led to embolism originating from a central source and traveling to the cerebellum. Only one prior study that we are aware of has reported ischemic stroke in lecanemab-treated patients [15], although a previous case report also indicates ischemic stroke in a patient receiving an earlier generation drug, bapineuzumab [18]. In the lecanemab case, a 71-year-old male who is heterozygous with ApoE3 and ApoE4 presented with bifrontal headache a few days after his third infusion of lecanemab, and the MRI was consistent with severe ARIA-E and mild ARIA-H and a small ischemic stroke in the right occipital lobe. He had continuous EEG that revealed three focal electrographic seizures with no clinical accompaniments. After two weeks, his repeated MRI showed another new punctate stroke in the same area. The patient's stroke workup was negative, and the impression was that it was secondary to ongoing ARIA-E-related inflammation. She was treated with steroids.\u003c/p\u003e \u003cp\u003eARIA's pathophysiology is hypothesized to be stimulated by anti-amyloid therapy, which mobilize Aβ into the vasculature and increase its deposition in perivascular spaces, thereby disrupting vascular stability and leading to blood leakage and edema and, or hemorrhages, which is similar to CAA and cerebral amyloid angiopathy-related inflammation (CCAri) [19, 20]. CCAri was found to be associated with T-cell infiltration, microglial activation, and anti-amyloid autoantibody production [21, 22]. In more severe cases, it can develop into Aβ-related angiitis with lymphocytic infiltration and granulomatous changes [23]. Just as CAA predisposes to both ischemic and hemorrhagic stroke [24], both patients described above that received lecanemab had both ischemic and hemorrhagic complications seen after starting lecanemab.\u003c/p\u003e \u003cp\u003eThese reports serve as points of caution for the initiation of lecanemab in elderly patients, particularly if there is evidence of previous ischemic stroke on imaging. Aggressive workup of stroke risk factors prior to initiating lecanemab or similar antibodies may be warranted. If anti-amyloid therapy does predispose to ischemic stroke, this could pose a significant problem, given the concerns around thrombolysis or dual antiplatelet therapy in patients that have also had ARIA [25]. Therefore, future work should continue to prospectively assess ischemic stroke risk after initiating anti-amyloid therapy.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eAlzheimer\u0026apos;s Disease (AD), amyloid precursor protein (APP), apolipoprotein E (ApoE), amyloid-related imaging abnormalities (ARIA) Montreal Cognitive Assessment (MoCA), Functional Activities Questionnaire (FAQ), Amyloid positron emission tomography (amyloid PET), Diffusion Weighted Imaging (DWI), electrocardiogram (ECG), magnetic resonance angiography (MRA), Electroencephalogram (EEG), cerebral amyloid angiopathy-related inflammation (CCAri).\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics Approval, Consent to Participate and Consent to Publish\u003c/strong\u003e: This case report was conducted in accordance with ethical standards. Consent for publication was obtained from the patient and her husband.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of Data and Materials\u003c/strong\u003e: The data supporting the findings of this case report are available upon request from the corresponding author.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e: D.A.L has previously received consulting fees from Eisai Pharmaceuticals. All other authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e: No funding was received for the preparation or publication of this manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; Contributions\u003c/strong\u003e: H.A. was responsible for the conceptualization and design of the case report, patient assessment, data collection (including medical history, clinical examination, and diagnostic tests), and drafting the initial manuscript. D.A.L. provided clinical oversight, managed the case, and contributed to the interpretation of medical data and critical revision of the manuscript for intellectual content and clinical accuracy. Both authors have approved the final version of the manuscript and are accountable for all aspects of the work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e: None.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eKnopman, D., H. Amieva, R. Petersen, G. Ch\u0026eacute;telat, D. Holtzman, B. Hyman, R. Nixon and D. Jones, \u003cem\u003eAlzheimer Disease Nat Rev Dis Primers 7: 33\u003c/em\u003e. 2021.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eThinakaran, G. and E.H. Koo (2008) \u003cem\u003eAmyloid precursor protein trafficking, processing, and function.\u003c/em\u003e \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eJournal of Biological Chemistry\u003c/span\u003e. \u003cspan type=\"BoldUnderline\" class=\"BoldUnderline\" name=\"Emphasis\"\u003e283\u003c/span\u003e(44): p. 29615\u0026ndash;29619\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSpires-Jones, T.L. and B.T. Hyman (2014) \u003cem\u003eThe intersection of amyloid beta and tau at synapses in Alzheimer\u0026rsquo;s disease.\u003c/em\u003e \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eNeuron\u003c/span\u003e. \u003cspan type=\"BoldUnderline\" class=\"BoldUnderline\" name=\"Emphasis\"\u003e82\u003c/span\u003e(4): p. 756\u0026ndash;771\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKim, J., J.M. Basak and D.M. Holtzman (2009) \u003cem\u003eThe role of apolipoprotein E in Alzheimer's disease.\u003c/em\u003e \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eNeuron\u003c/span\u003e. \u003cspan type=\"BoldUnderline\" class=\"BoldUnderline\" name=\"Emphasis\"\u003e63\u003c/span\u003e(3): p. 287\u0026ndash;303\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHuynh, T.-P.V., A.A. Davis, J.D. Ulrich and D.M. Holtzman (2017) \u003cem\u003eApolipoprotein E and Alzheimer's disease: the influence of apolipoprotein E on amyloid-β and other amyloidogenic proteins: Thematic Review Series: ApoE and Lipid Homeostasis in Alzheimer's Disease.\u003c/em\u003e \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eJournal of lipid research\u003c/span\u003e. \u003cspan type=\"BoldUnderline\" class=\"BoldUnderline\" name=\"Emphasis\"\u003e58\u003c/span\u003e(5): p. 824\u0026ndash;836\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTucker, S., C. M\u0026ouml;ller, K. Tegerstedt, A. Lord, H. Laudon, J. Sj\u0026ouml;dahl, L. S\u0026ouml;derberg, E. Spens, C. Sahlin and E.R. Waara (2015) \u003cem\u003eThe murine version of BAN2401 (mAb158) selectively reduces amyloid-β protofibrils in brain and cerebrospinal fluid of tg-ArcSwe mice.\u003c/em\u003e \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eJournal of Alzheimer's Disease\u003c/span\u003e. \u003cspan type=\"BoldUnderline\" class=\"BoldUnderline\" name=\"Emphasis\"\u003e43\u003c/span\u003e(2): p. 575\u0026ndash;588\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVan Dyck, C.H., C.J. Swanson, P. Aisen, R.J. Bateman, C. Chen, M. Gee, M. Kanekiyo, D. Li, L. Reyderman and S. Cohen (2023) \u003cem\u003eLecanemab in early Alzheimer\u0026rsquo;s disease.\u003c/em\u003e \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eNew England Journal of Medicine\u003c/span\u003e. \u003cspan type=\"BoldUnderline\" class=\"BoldUnderline\" name=\"Emphasis\"\u003e388\u003c/span\u003e(1): p. 9\u0026ndash;21\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVukmir, R.B. (2024) \u003cem\u003eAmyloid-related imaging abnormalities (ARIA): diagnosis, management, and care in the setting of amyloid‐modifying therapy.\u003c/em\u003e \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eAnnals of clinical and translational neurology\u003c/span\u003e. \u003cspan type=\"BoldUnderline\" class=\"BoldUnderline\" name=\"Emphasis\"\u003e11\u003c/span\u003e(7): p. 1669\u0026ndash;1680\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eToledo, J.B., S.E. Arnold, K. Raible, J. Brettschneider, S.X. Xie, M. Grossman, S.E. Monsell, W.A. Kukull and J.Q. Trojanowski (2013) \u003cem\u003eContribution of cerebrovascular disease in autopsy confirmed neurodegenerative disease cases in the National Alzheimer\u0026rsquo;s Coordinating Centre.\u003c/em\u003e \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eBrain\u003c/span\u003e. \u003cspan type=\"BoldUnderline\" class=\"BoldUnderline\" name=\"Emphasis\"\u003e136\u003c/span\u003e(9): p. 2697\u0026ndash;2706\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVan Groen, T., K. Puurunen, H.-M. M\u0026auml;ki, J. Sivenius and J. Jolkkonen (2005) \u003cem\u003eTransformation of diffuse β-amyloid precursor protein and β-amyloid deposits to plaques in the thalamus after transient occlusion of the middle cerebral artery in rats.\u003c/em\u003e \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eStroke\u003c/span\u003e. \u003cspan type=\"BoldUnderline\" class=\"BoldUnderline\" name=\"Emphasis\"\u003e36\u003c/span\u003e(7): p. 1551\u0026ndash;1556\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGarcia-Alloza, M., J. Gregory, K.V. Kuchibhotla, S. Fine, Y. Wei, C. Ayata, M.P. Frosch, S.M. Greenberg and B.J. Bacskai (2011) \u003cem\u003eCerebrovascular lesions induce transient β-amyloid deposition.\u003c/em\u003e \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eBrain\u003c/span\u003e. \u003cspan type=\"BoldUnderline\" class=\"BoldUnderline\" name=\"Emphasis\"\u003e134\u003c/span\u003e(12): p. 3697\u0026ndash;3707\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMarchesi, V.T. (2011) \u003cem\u003eAlzheimer's dementia begins as a disease of small blood vessels, damaged by oxidative-induced inflammation and dysregulated amyloid metabolism: implications for early detection and therapy.\u003c/em\u003e \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eThe FASEB Journal\u003c/span\u003e. \u003cspan type=\"BoldUnderline\" class=\"BoldUnderline\" name=\"Emphasis\"\u003e25\u003c/span\u003e(1): p. 5\u0026ndash;13\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIturria-Medina, Y., R.C. Sotero, P.J. Toussaint, J.M. Mateos-P\u0026eacute;rez and A.C. Evans (2016) \u003cem\u003eEarly role of vascular dysregulation on late-onset Alzheimer\u0026rsquo;s disease based on multifactorial data-driven analysis.\u003c/em\u003e \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eNature communications\u003c/span\u003e. \u003cspan type=\"BoldUnderline\" class=\"BoldUnderline\" name=\"Emphasis\"\u003e7\u003c/span\u003e(1): p. 11934\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLowerison, M.R., N.V.C. Sekaran, Z. Dong, X. Chen, Q. You, D.A. Llano and P. Song (2024) \u003cem\u003eSuper-resolution ultrasound reveals cerebrovascular impairment in a mouse model of Alzheimer's Disease.\u003c/em\u003e \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eJournal of Neuroscience\u003c/span\u003e. \u003cspan type=\"BoldUnderline\" class=\"BoldUnderline\" name=\"Emphasis\"\u003e44\u003c/span\u003e(9)\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGibson, A.W., H. Elser, M. Rosso, E.J. Cornblath, Y. Fonkeu, S. Prasad, A. Rothstein, I.M. Nasrallah, D.A. Wolk and M.H. Guo (2024) \u003cem\u003eIschemic stroke associated with amyloid-related imaging abnormalities in a patient treated with lecanemab.\u003c/em\u003e \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eAlzheimer's \u0026amp; Dementia\u003c/span\u003e. \u003cspan type=\"BoldUnderline\" class=\"BoldUnderline\" name=\"Emphasis\"\u003e20\u003c/span\u003e(11): p. 8192\u0026ndash;8197\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSolopova, E., W. Romero-Fernandez, H. Harmsen, L. Ventura-Antunes, E. Wang, A. Shostak, J. Maldonado, M.J. Donahue, D. Schultz and T.M. Coyne (2023) \u003cem\u003eFatal iatrogenic cerebral β-amyloid-related arteritis in a woman treated with lecanemab for Alzheimer\u0026rsquo;s disease.\u003c/em\u003e \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eNature communications\u003c/span\u003e. \u003cspan type=\"BoldUnderline\" class=\"BoldUnderline\" name=\"Emphasis\"\u003e14\u003c/span\u003e(1): p. 8220\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCastellani, R.J., E.D. Shanes, M. McCord, N.J. Reish, M.E. Flanagan, M.M. Mesulam and P. Jamshidi (2023) \u003cem\u003eNeuropathology of Anti-Amyloid-β Immunotherapy: A Case Report.\u003c/em\u003e \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eJ Alzheimers Dis\u003c/span\u003e. \u003cspan type=\"BoldUnderline\" class=\"BoldUnderline\" name=\"Emphasis\"\u003e93\u003c/span\u003e(2): p. 803\u0026ndash;813\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRoher, A.E., C.L. Maarouf, I.D. Daugs, T.A. Kokjohn, J.M. Hunter, M.N. Sabbagh and T.G. Beach (2011) \u003cem\u003eNeuropathology and amyloid-β spectrum in a bapineuzumab immunotherapy recipient.\u003c/em\u003e \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eJ Alzheimers Dis\u003c/span\u003e. \u003cspan type=\"BoldUnderline\" class=\"BoldUnderline\" name=\"Emphasis\"\u003e24\u003c/span\u003e(2): p. 315\u0026thinsp;\u0026minus;\u0026thinsp;25.PMC3172868\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKozberg, M.G., I. Yi, W.M. Freeze, C.A. Auger, A.A. Scherlek, S.M. Greenberg and S.J. van Veluw (2022) \u003cem\u003eBlood\u0026ndash;brain barrier leakage and perivascular inflammation in cerebral amyloid angiopathy.\u003c/em\u003e \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eBrain Communications\u003c/span\u003e. \u003cspan type=\"BoldUnderline\" class=\"BoldUnderline\" name=\"Emphasis\"\u003e4\u003c/span\u003e(5): p. fcac245\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBilodeau, P.A., J.R. Dickson and M.G. Kozberg (2024) \u003cem\u003eThe Impact of Anti-Amyloid Immunotherapies on Stroke Care.\u003c/em\u003e \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eJournal of Clinical Medicine\u003c/span\u003e. \u003cspan type=\"BoldUnderline\" class=\"BoldUnderline\" name=\"Emphasis\"\u003e13\u003c/span\u003e(5): p. 1245\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePiazza, F., S.M. Greenberg, M. Savoiardo, M. Gardinetti, L. Chiapparini, I. Raicher, R. Nitrini, H. Sakaguchi, M. Brioschi and G. Billo (2013) \u003cem\u003eAnti\u0026ndash;amyloid β autoantibodies in cerebral amyloid angiopathy\u0026ndash;related inflammation: implications for amyloid-modifying therapies.\u003c/em\u003e \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eAnnals of neurology\u003c/span\u003e. \u003cspan type=\"BoldUnderline\" class=\"BoldUnderline\" name=\"Emphasis\"\u003e73\u003c/span\u003e(4): p. 449\u0026ndash;458\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKinnecom, C., M. Lev, L. Wendell, E. Smith, J. Rosand, M. Frosch and S. Greenberg (2007) \u003cem\u003eCourse of cerebral amyloid angiopathy\u0026ndash;related inflammation.\u003c/em\u003e \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eNeurology\u003c/span\u003e. \u003cspan type=\"BoldUnderline\" class=\"BoldUnderline\" name=\"Emphasis\"\u003e68\u003c/span\u003e(17): p. 1411\u0026ndash;1416\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eScolding, N.J., F. Joseph, P.A. Kirby, I. Mazanti, F. Gray, J. Mikol, D. Ellison, D.A. Hilton, T.L. Williams and J.M. MacKenzie (2005) \u003cem\u003eAβ-related angiitis: primary angiitis of the central nervous system associated with cerebral amyloid angiopathy.\u003c/em\u003e \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eBrain\u003c/span\u003e. \u003cspan type=\"BoldUnderline\" class=\"BoldUnderline\" name=\"Emphasis\"\u003e128\u003c/span\u003e(3): p. 500\u0026ndash;515\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXiong, L., S.J. Van Veluw, N. Bounemia, A. Charidimou, M. Pasi, G. Boulouis, Y.D. Reijmer, A.-K. Giese, S. Davidsdottir and P. Fotiadis (2018) \u003cem\u003eCerebral cortical microinfarcts on magnetic resonance imaging and their association with cognition in cerebral amyloid angiopathy.\u003c/em\u003e \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eStroke\u003c/span\u003e. \u003cspan type=\"BoldUnderline\" class=\"BoldUnderline\" name=\"Emphasis\"\u003e49\u003c/span\u003e(10): p. 2330\u0026ndash;2336\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGreenberg, S.M., H.J. Aparicio, K.L. Furie, M.S. Goyal, J.D. Hinman, M. Kozberg, A. Leonard, M.J. Fisher, A.H.A.S. Council, C.o. Cardiovascular, S. Nursing, and C.o.C. Cardiology (2024) \u003cem\u003eVascular Neurology Considerations for Antiamyloid Immunotherapy: A Science Advisory From the American Heart Association.\u003c/em\u003e \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eStroke\u003c/span\u003e,\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Alzheimer’s Disease, Lecanemab, ischemic stroke","lastPublishedDoi":"10.21203/rs.3.rs-5845699/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5845699/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eAmyloid-lowering therapy has been previously associated with the formation of cerebral edema and/or microhemorrhage, often picked up on MRI and referred to as amyloid-related imaging abnormalities, or ARIA.\u003c/p\u003e\u003ch2\u003eCase presentation:\u003c/h2\u003e \u003cp\u003eWe describe a case of a patient with Alzheimer\u0026rsquo;s Disease treated with the amyloid-lowering drug lecanemab who developed both ARIA-H and ARIA-E, and multiple ischemic infarctions.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThis finding, in conjunction with previous reports of ischemic infarction in the setting of anti-amyloid therapy, suggests that amyloid-lowering therapy may predispose individuals to both hemorrhagic and ischemic infarction. This result is discussed in the context of microvascular pathology known to occur in the setting of Alzheimer\u0026rsquo;s Disease.\u003c/p\u003e","manuscriptTitle":"Multiple Ischemic Strokes in a Patient Treated with Lecanemab: A Case Report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-01-28 15:19:09","doi":"10.21203/rs.3.rs-5845699/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"3f5bac17-5eb9-4ea4-8e7d-da71ed0c8716","owner":[],"postedDate":"January 28th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-02-17T11:53:44+00:00","versionOfRecord":[],"versionCreatedAt":"2025-01-28 15:19:09","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5845699","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5845699","identity":"rs-5845699","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}