MicroRNA-Mediated Inhibition of Amyloid Beta Protein Synthesis in Alzheimer’s Disease: A Research Protocol

Abstract

Introduction: Alzheimer’s disease (AD) is a currently incurable neurodegenerative disorder that is defined by the buildup
of amyloid beta peptide (Aβ) plaques in the brain. Herein, we aim to investigate two microRNA (miRNA), miR-106b and miR-153, for their ability to inhibit the synthesis of amyloid beta precursor protein. Since miR-106b and miR-153 are also deficient in AD patients, we hypothesize that increasing their concentrations in the brain will reduce plaque development, thereby ameliorating AD symptoms.

Methods: Six groups of mice will be reared: a control group of healthy C57BL/6J mice; a control group of diseased B6.
Cg-Tg(Thy1-APP)3Somm/J mice; 2 control groups of B6.Cg-Tg(Thy1-APP)3Somm/J mice, one treated an empty mini-osmotic pump, the other treated with functionless miRNA; and two treatment groups of B6.Cg-Tg(Thy1-APP)3Somm/J mice treated with miR-106b and miR-153 each. Then, a Morris water maze test and ELISA analysis will be conducted on each group to determine the effectiveness of the miRNA treatment at reducing Aβ plaque and AD symptoms.

Discussion: As a proof of concept study, this experiment may determine whether miRNAs can alleviate AD symptoms and plaque development. There may be limitations regarding the applicability of murine models, as well as the implementation of induced AD in the genetically modified mice. The results of each experimental group will be compared using an ANOVA, and qualitatively for improvement of cognitive functioning.

Conclusion: This experiment suggests an approach to counter the deleterious effects of AD. Future studies may investigate less invasive methods of administering miRNA treatments.