The identification of mechanisms associated with Alzheimer's disease (AD) development in mild cognitive impairment (MCI) would be of great usefulness to clarify AD pathogenesis and to develop preventive and therapeutic strategies. In this study, blood levels of the candidate microRNAs (small noncoding RNAs that play a pivotal role in gene expression) miR-146a, miR-181a, miR-181b, miR-24-3p, miR-186a, miR-101, miR-339, miR-590, and miR-22 have been investigated for association to AD conversion within 2 years in a group of 45 patients with MCI. Baseline miR-146a (p = 0.036) and miR-181a (p = 0.026) showed a significant upregulation in patients with MCI who later converted to AD. These alterations were related to AD hallmarks: a significant negative correlation was found with amyloid beta cerebrospinal fluid concentration for miR-146a (p = 0.006) and miR-181a (p = 0.001). Moreover, higher levels of miR-146a were associated to apolipoprotein E ε4 allele presence, smaller volume of the hippocampus (p = 0.045) and of the CA1 (p = 0.013) and the subiculum (p = 0.027) subfields. Increased levels of miR-146a (p = 0.031) and miR-181a (p = 0.002) were also linked with diffusivity alterations in the cingulum. These data support a role for miR-146a and miR-181a in the mechanisms of AD progression.