Determining Proteomic Changes Related to Alzheimer's Disease and Circadian Disruption

Alzheimer's Disease is a neurodegenerative disease which results in progressive loss of neurons in the central or peripheral nervous systems (Wilson et. al. 2023) as well as progressive loss of motor functions. Alzheimer's is also characterized in its uniquely dysfunctional and dysregulated circadian rhythms (Ahmad, et al. 2022). Along with age, circadian rhythm disruption (irregularities) may exacerbate the negative traits of Alzheimer's, causing further impairment (Madamanchi et al. 2025). Our research characterizes the proteomic activity and the role of circadian rhythm disruptions in Alzheimer's disease progression via analysis of protein expression and oscillations. Using four male and female mice groups with and without circadian disruption and Alzheimer's-like qualities, our results showcased protein and sex specific impact on circadian rhythms. We extracted commonalities and differences in protein expression of different comparisons of experimental groups using correlation and adjacency matrices, highlighting specifically which proteins remained circadian, became circadian, or lost circadian rhythmicity throughout oscillations. Analysis demonstrated that proteins in female groups exhibited more proteins remaining and became co-expressed in circadian rhythms than male groups on average. The leiden algorithm was implemented to cluster and analyze the data from the adjacency matrices. The data was partitioned, clusters were created within each partition, and we were able to analyze the modularity, standard deviation, and period values of the clusters. This was to produce code in order to determine how rhythmically similar proteins clustered together are, which we achieved. From our analyses we were able to see that female mice shared 124 conserved circadian proteins across every experimental group, and that male mice shared 140. We isolated specific proteins from the String database to analyze, and found the gene APOE, which is strongly associated with the onset of Alzheimer's disease, was present in every cluster and relevant across every experimental group. We were able to use our code for cluster analysis to develop tools for seeing which proteins were clustered similarly alongside APOE. In all, our adjacency matrix and clustering model scripts were created as tools for analyzing proteomic activity and the role of circadian rhythm disruption in Alzheimer's disease.