The complexity of neurodegenerative processes and the human nervous system hinder progress towards a comprehensive understanding of both. Much of our advancements in understanding disease has been through the use of human post-mortem tissues. As these are only representative of the end stage of life, it is difficult to differentiate between chronic long-term consequences of disease (ie, neurofibrillary tangles) and potential regulators which directly drive pathological processes. Using small animal model systems has limitations resulting in high failure to translate directly from rodent-derived findings to an effective treatment. Therefore, we have created a gene-edited large animal model of CLN1 (Batten’s disease)-a form of childhood dementia. This model allows us to map the molecular alterations in response to altered dose of the causative PPT1 gene, throughout disease progression and compare differentially vulnerable brain regions. A total of 7972 proteins were identified in all sheep brain tissue samples using single shot mass spectrometry and 5689 proteins were mappable for pathway analysis. Based on unique and common proteins, a dose dependant dysfunction was reported in pathways associated with glucose and lipid metabolism, mitochondrial function, and cellular homeostasis. We believe the data from this research will (1) aid in differentiating between regulators of pathology (2) determine chronic markers of disease and other age-related changes (3) identifying molecular targets for therapeutics.