Abstract
Extracellular circulating microRNAs (miRNAs) have been discussed as potential biomarkers for Alzheimer's disease (AD) diagnosis. As the retina is a part of the CNS, we hypothesize that miRNAs expression levels in the brain, particularly neocortex-hippocampus, eye tissues, and tear fluids are similar at different stages of AD progression. Ten miRNA candidates were systematically investigated in transgenic APP-PS1 mice, noncarrier siblings, and C57BL/6J wild-type controls at young and old ages. Relative expression levels of tested miRNAs revealed a similar pattern in both APP-PS1 mice and noncarrier siblings when compared with age- and sex-matched wild-type controls. However, the differences seen in expression levels between APP-PS1 mice and noncarrier siblings could possibly have resulted from underlying molecular etiology of AD. Importantly, miRNAs associated with amyloid beta (Aβ) production (-101a, -15a, and -342) and proinflammation (-125b, -146a, and -34a) showed significant up-regulations in the tear fluids with disease progression, as tracked by cortical Aβ load and reactive astrogliosis. Overall, for the first time, the translational potential of up-regulated tear fluid miRNAs associated with AD pathogenesis was comprehensively demonstrated.