PT - JOURNAL ARTICLE AU - Printha Wijesinghe AU - Jeanne Xi AU - Jing Cui AU - Matthew Campbell AU - Wellington Pham AU - Joanne A Matsubara TI - MicroRNAs in tear fluids predict underlying molecular changes associated with Alzheimer’s disease AID - 10.26508/lsa.202201757 DP - 2023 Jun 01 TA - Life Science Alliance PG - e202201757 VI - 6 IP - 6 4099 - https://www.life-science-alliance.org/content/6/6/e202201757.short 4100 - https://www.life-science-alliance.org/content/6/6/e202201757.full SO - Life Sci. Alliance2023 Jun 01; 6 AB - 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.