Cockayne Syndrome (CS) is a rare, autosomal recessive, neurodegenerative disorder characterized by growth defects, cognitive disability, and deficiencies which contribute to an overall presentation of premature aging (including dementia) in patients. This autosomal recessive disease is characterized by an inability to repair DNA, when editing is necessary, during normal DNA replication and transcription. Using a healthy control and CS patient derived fibroblast cells, as well as a stable isotope protein labeling method, we performed a protein-based analysis of the disease. This enabled direct comparisons between the expression levels of proteins in CS and healthy controls. Our analysis revealed dramatic parallels between how proteins are expressed in CS and how these proteins have been previously shown to be associated with Alzheimer’s disease (AD). The majority of these proteins are thought to be involved in both mitochondrial dysfunction and the upregulation of glycolysis. They are also involved in the handling of misfolded proteins, which has dire consequences in neurons and manifests as Alzheimer’s type dementia. Preliminary functional characterizations in CS and AD cells have further confirmed novel similarities between the two disorders, which would allow for the design of therapies aimed at treating common effectors for both diseases.