A whole-brain model of amyloid beta accumulation and cerebral hypoperfusion in Alzheimer’s disease

Corti M, Ahern A, Goriely A, Kuhl E, Antonietti PF (2026)

Publication Type: Journal article

Publication year: 2026

Journal

Computer Methods in Applied Mechanics and Engineering Elsevier

Book Volume: 461

Article Number: 119196

DOI: 10.1016/j.cma.2026.119196

Abstract

Accumulation of amyloid beta proteins is a defining feature of Alzheimer’s disease, and is usually accompanied by cerebrovascular pathology. Evidence suggests that amyloid beta and cerebrovascular pathology are mutually reinforcing; in particular, amyloid beta suppresses perfusion by constricting capillaries, and hypoperfusion promotes the production of amyloid beta. Here, we propose a whole-brain model coupling amyloid beta and blood vessel through a hybrid model consisting of a reaction–diffusion system for the protein dynamics and porous-medium model of blood flow within and between vascular networks: arterial, capillary and venous. We discretize the resulting parabolic–elliptic system of PDEs by means of a high-order discontinuous Galerkin method in space and an implicit Euler scheme in time. Simulations in realistic brain geometries demonstrate the emergence of multistability, implying that a sufficiently large pathogenic protein seed is necessary to trigger a disease outbreak. Motivated by the ‘two-hit vascular hypothesis’ of Alzheimer’s disease that hypoperfusion due to vascular damage triggers amyloid beta pathology, we also demonstrate that localized hypoperfusion, in response to injury, can destabilize the healthy steady state and trigger brain-wide disease outbreak.

Authors with CRIS profile

Ellen Kuhl Lehrstuhl für Technische Mechanik (LTM)

Involved external institutions

Politecnico di Milano IT Italy (IT) University of Oxford GB United Kingdom (GB)

How to cite

APA:

Corti, M., Ahern, A., Goriely, A., Kuhl, E., & Antonietti, P.F. (2026). A whole-brain model of amyloid beta accumulation and cerebral hypoperfusion in Alzheimer’s disease. Computer Methods in Applied Mechanics and Engineering, 461. https://doi.org/10.1016/j.cma.2026.119196

MLA:

Corti, Mattia, et al. "A whole-brain model of amyloid beta accumulation and cerebral hypoperfusion in Alzheimer’s disease." Computer Methods in Applied Mechanics and Engineering 461 (2026).

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