RT Journal Article
SR Electronic
T1 MicroRNAs in tear fluids predict underlying molecular changes associated with Alzheimer’s disease
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202201757
DO 10.26508/lsa.202201757
VO 6
IS 6
A1 Wijesinghe, Printha
A1 Xi, Jeanne
A1 Cui, Jing
A1 Campbell, Matthew
A1 Pham, Wellington
A1 Matsubara, Joanne A
YR 2023
UL http://www.life-science-alliance.org/content/6/6/e202201757.abstract
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.