Alzheimer’s disease is characterised by the spreading of misfolded proteins and progressive structural changes in the brain. Despite significant clinical research, understanding how microscopic protein dynamics translate into macroscopic tissue degeneration remains a major challenge. In this work, we present a three-dimensional, finite element-based computational framework to model disease progression by combining multi-protein transport and brain tissue deformation within anatomically realistic geometries. The propagation of toxic tau and amyloid-β proteins is described using reaction–diffusion equations of the Fisher-Kolmogorov type, incorporating prion-like growth mechanisms and anisotropic transport along white matter fibre tracts. Brain atrophy is represented through a hyperelastic constitutive model driven by protein-dependent volume loss. Subject-specific simulations are achieved through an automated preprocessing pipeline that generates finite element meshes and reconstructs axonal orientation fields from medical imaging data. The model reproduces key morphological patterns observed in Alzheimer’s disease and shows good quantitative agreement with longitudinal imaging measurements. Overall, the proposed framework offers an extensible computational platform for studying Alzheimer’s disease progression across subject-specific brain geometries.