Author Identifier (ORCID)
Kevin Taddei: https://orcid.org/0000-0002-8106-7957
Samantha L. Gardener: https://orcid.org/0000-0002-1933-5260
Ralph N. Martins: https://orcid.org/0000-0002-4828-9363
Abstract
Background: Apolipoprotein E (APOE) genotype influences the presence, course and severity of sporadic cerebral amyloid angiopathy (sCAA). We investigated the effect of the APOE ε4-allele on clinical and neuroradiological outcomes in mutation-carriers with Dutch-type hereditary (D-)CAA. Methods: Participants with D-CAA from a prospective cohort study, with data collected on history of symptomatic intracerebral hemorrhages (sICH) and vascular risk factors, underwent 3 Tesla magnetic resonance imaging (MRI) scans to assess macrobleeds, cerebral microbleeds (CMBs), cortical superficial siderosis (cSS), enlarged perivascular spaces (EPVS), white matter hyperintensity (WMH) volume and WMH multispot lesions. Global cognition was measured using Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE) scores. Associations between ≥1 APOE ε4-allele and age of first sICH, time to recurrence, cognition and radiological data were analyzed with adjustments for confounders. Results: Eighty-one participants (mean age 47 years, 54% women, 38% with sICH history) were included. The APOE ε4-allele was not associated with earlier sICH onset (median age 56 versus 57 years; p = 0.6) or time to recurrence (5.0 versus 3.9 years; p = 0.4), nor was it associated with macrobleeds (β 2.0; 95%CI 2.4- -2.7; p = 0.4), CMBs (β 2.9; 95%CI 1.0-8.9; p = 0.06), cSS (aOR 0.5; 95%CI 0.1-2.0; p = 0.3), EPVS (aOR 0.4; 95%CI 0.1-1.5; p = 0.6), WMH volume (β 6.8; 95%CI -1.9-15.4; p = ), a multispot pattern (OR 0.7; 95%CI 0.2-2.7, p = 0.6), or cognition (β -0.3; 95%CI -0.4- -0.5; p = 0.5). Conclusion: APOE ε4 does not affect key clinical parameters or D-CAA neuroradiological markers and therefore does not explain the large variation in disease course in D-CAA.
Keywords
Apolipoprotein E, cerebral amyloid angiopathy, intracerebral hemorrhage, stroke
Document Type
Journal Article
Date of Publication
4-1-2026
Volume
35
Issue
4
PubMed ID
41707816
Publication Title
Journal of Stroke and Cerebrovascular Diseases
Publisher
Elsevier
School
Centre of Excellence for Alzheimer's Disease Research and Care / School of Medical and Health Sciences
Funders
Dutch Heart Foundation (2016T086) / TRACK-D-CAA-Consortium
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
First Page
108593
Comments
Van Der Plas, M. C., Van Dort, R., Rasing, I., Long, Y., Van Zwet, E. W., Van Osch, M. J., Sohrabi, H. R., Taddei, K., Gardener, S. L., Martins, R. N., Greenberg, S. M., Terwindt, G. M., Van Walderveen, M. A., & Wermer, M. J. (2026). The association of Apolipoprotein E ε4 with symptomatic intracerebral hemorrhage, MRI markers and cognition in Dutch-type hereditary cerebral amyloid angiopathy. Journal of Stroke and Cerebrovascular Diseases, 35(4), 108593. https://doi.org/10.1016/j.jstrokecerebrovasdis.2026.108593