Positron emission tomography (PET) molecular biomarkers and diffusion magnetic resonance imaging (dMRI) derived information show associations and highly complementary information in a number of neurodegenerative conditions, including Alzheimer’s disease. Diffusion MRI provides valuable information about the microstructure and structural connectivity (SC) of the brain which could guide and improve the PET image reconstruction when such associations exist. However, this potental has not been previously explored. In the present study, we propose a CONNectome-based non-local means one-atep late maximum a posteriori (CONN-NLM-OSLMAP) method, which allows diffusion MRI-derived connectivity information to be incorporated into the PET iterative image reconstruction process, thus regularising the estimated PET images. The proposed method was evaluated using a realistic tau-PET/MRI simulated phantom, demonstrating more effective noise reduction and lesion contrast improvement, as well as the lowest overall bias compared with both a median filter applied as an alternative regulariser and CONNectome-based non-local means as a post-reconstruction filter. By adding complementary SC information from diffusion MRI, the proposed regularisation method offers more useful and targeted denoising and regularisation, demonstrating the feasibility and effectiveness of integrating connectivity information into PET image reconstruction.