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There are synergistic effects of Aβ and tau protein in Alzheimer’s disease. Aβ_1–42 protofibril seeds induce conversion of human tau protein into β-sheet-rich toxic tau oligomers. However, the molecular mechanisms underlying such a conformational conversion are unclear. Here, we use extensive all atom replica exchange molecular dynamics simulations to investigate the effects of preformed Aβ_1–42 protofibril on two monomeric tau constructs: K18 and K19. We found that Aβ oligomer stretches tau conformation and drastically reduces the metastable secondary structures/hydrogen bonding/salt-bridge networks in tau monomers and exposes their fibril nucleating motifs ²⁷⁵VQIINK²⁸⁰ and ³⁰⁶VQIVYK³¹¹. Aβ interacting patches around Tyr10/Ile41 contribute significantly to the interactions with K18 and K19. Aβ cross-seeded tau aggregation can adopt a “stretching-and-packing” mechanism, paving the way for the …