Coagulation factor XII deficiency alleviates vascular dysfunction and cognitive impairment in a mouse model of cerebral β-amyloidosis and cerebral amyloid angiopathy

Rouault, Marie; Kindler, Diana Rita; Ni, Ruiqing; Liberale, Luca; Seiler, Raoul; Ielacqua, Giovanna D.; Nitsch, Roger; Pryce, Christopher; Camici, Giovanni G.; Kulic, Luka; Klohs, Jan

Coagulation factor XII deficiency alleviates vascular dysfunction and cognitive impairment in a mouse model of cerebral β-amyloidosis and cerebral amyloid angiopathy

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Item Type:	Article
Title:	Coagulation factor XII deficiency alleviates vascular dysfunction and cognitive impairment in a mouse model of cerebral β-amyloidosis and cerebral amyloid angiopathy
Creators:	Rouault, Marie, Kindler, Diana Rita, Ni, Ruiqing, Liberale, Luca, Seiler, Raoul, Ielacqua, Giovanna D. ORCID: https://orcid.org/0000-0002-0816-6617, Nitsch, Roger, Pryce, Christopher, Camici, Giovanni G., Kulic, Luka and Klohs, Jan
Abstract:	Amyloid-β (Aβ) can activate the factor XII (FXII)-driven contact system, which exerts several downstream effects on Alzheimer's disease (AD) pathology associated with cognitive impairment. Here, using genetically modified FXII deficient mice crossed with arcAβ mice, we show that genetic deletion of FXII ameliorates β-amyloidosis-mediated susceptibility to arterial thrombus formation, blood-brain barrier leakage, and cerebral microbleed load. Furthermore, we show that genetic deletion of FXII improves cognitive deficits, without affecting Aβ deposition. Thus, the FXII-driven contact system constitutes an important pathway contributing to vascular dysfunction and cognitive impairment in AD, independent of Aβ neuropathology, with important implications for the diagnosis and treatment of the disease.
Keywords:	Alzheimer's Disease, Coagulation, Hageman Factor, Vascular Dysfunction, Cerebral Microbleeds, Blood-Brain Barrier, Thrombosis, Animals, Mice
Source:	Aging Brain
ISSN:	2589-9589
Publisher:	Elsevier
Volume:	10
Page Range:	100167
Number of Pages:	1
Date:	25 August 2026
Official Publication:	https://doi.org/10.1016/j.nbas.2026.100167
PubMed:	View item in PubMed

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