Casquero-Veiga, MartaCeron, CarlosCortes-Canteli, Marta2025-07-232025-07-232025-05-09Curr Opin Cell Biol. 2025 May 9:95:102528.https://hdl.handle.net/20.500.12105/26844Alzheimer's disease (AD) is characterized by a multifactorial pathophysiology. Beyond its classical hallmarks, growing evidence highlights vascular contributions, including hemostatic dysregulation and a prothrombotic state in AD. This review focuses on recent findings concerning two key blood clot components-fibrin(ogen) and platelets-and their roles in AD pathology, including fibrinogen's abnormal accumulation in the AD brain, its interaction with amyloid-β, together with the associated impacts on clot stability, vascular occlusion, and neuroinflammation; and the potential switch of platelets along the AD continuum from protective to deleterious. This review provides an update on the interplay between vascular dysfunction and AD, underscoring the need for comprehensive integrative research to address AD's complexity and advocating for personalized approaches to tackle this multifaceted disorder.This work was funded by grant JPND2020-568-025, an EU Joint Programme-Neurodegenerative Disease Research (JPND) project supported through the Spanish National Institute of Health Carlos III (ISCIII) under the aegis of JPND (project AC20/00077, cofunded by the European Regional Development Fund “A way to make Europe”); and by grant CNS2023- 144316 funded by the MCIN/AEI/10.13039/501100011033 and by the EU NextGenerationEU/PRTR. CNIC is a Severo Ochoa Center of Excellence (CEX2020-001041-S) and is supported by the ISCIII, the Spanish Ministry for Science and Innovation, and Pro-CNIC Foundation. MCV is supported by a BrightFocus Foundation Postdoctoral Fellowship in Alzheimer’s Disease Research (A2023012F), and grant JDC2022-048922-I funded by MCIN/AEI/10.13039/ 501100011033 and the EU NextGenerationEU/PRTR.engVoRhttp://creativecommons.org/licenses/by-nc-nd/4.0/Attribution-NonCommercial-NoDerivatives 4.0 International40347710Current Opinion in Cell Biologyopen access