Misfolded proteins (MP) are a key component in aging and associated neurodegenerative disorders. For example, misfolded Amyloid-xc3x9f (Axc3x9f) and tau proteins are two neuropathogenic hallmarks of Alzheimers disease. Mechanisms underlying intra-brain MP propagation/deposition remain essentially uncharacterized. Here, is introduced an epidemic spreading model (ESM) for MP dynamics that considers propagation-like interactions between MP agents and the brains clearance response across the structural connectome. The ESM reproduces advanced Axc3x9f deposition patterns in the human brain (explaining 46xe2x88xbc56% of the variance in regional Axc3x9f loads, in 733 subjects from the ADNI database). Furthermore, this model strongly supports a) the leading role of Axc3x9f clearance deficiency and early Axc3x9f onset age during Alzheimers disease progression, b) that effective anatomical distance from Axc3x9f outbreak region explains regional Axc3x9f arrival time and Axc3x9f deposition likelihood, c) the multi-factorial impact of APOE e4 genotype, gender and educational level on lifetime intra-brain Axc3x9f propagation, and d) the modulatory impact of Axc3x9f propagation history on tau proteins concentrations, supporting the hypothesis of an interrelated pathway between Axc3x9f pathophysiology and tauopathy. To our knowledge, the ESM is the first computational model highlighting the direct link between structural brain networks, production/clearance of pathogenic proteins and associated intercellular transfer mechanisms, individual genetic/demographic properties and clinical states in health and disease. In sum, the proposed ESM constitutes a promising framework to clarify intra-brain region to region transference mechanisms associated with aging and neurodegenerative disorders. 