Background: Alzheimer’s disease is one of the leading health problems characterized
by the accumulation of Aβ and hyperphosphorylated tau that account for the senile
plaque formations causing extensive cognitive decline. Many of the clinical diagnoses
of Alzheimer’s disease are made in the late stages, when the pathological changes
have already progressed.
Objective: The objective of this study is to evaluate the promising therapeutic effects of a
natural compound, lycoramine, which has been shown to have therapeutic potential in
several studies and to understand its mechanism of action on the molecular level via differential
protein expression analyses.
Methods: Lycoramine and galantamine, an FDA approved drug used in the treatment of
mild to moderate AD, were administered to 12 month-old 5xFAD mice. Effects of the
compounds were investigated by Morris water maze, immunohistochemistry and label-
free differential protein expression analyses.
Results: Here we demonstrated the reversal of cognitive decline via behavioral testing
and the clearance of Aβ plaques. Proteomics analysis provided in-depth information on
the statistically significant protein perturbations in the cortex, hippocampus and cerebellum
sections to hypothesize the possible clearance mechanisms of the plaque formation
and the molecular mechanism of the reversal of cognitive decline in a transgenic mouse
model. Bioinformatics analyses showed altered molecular pathways that can be linked
with the reversal of cognitive decline observed after lycoramine administration but not
Conclusion: Lycoramine shows therapeutic potential to halt and reverse cognitive decline
at the late stages of disease progression, and holds great promise for the treatment of