Parkinson's Disease (PD) and Alzheimer's Disease (AD) are the two most prevalent neurodegenerative diseases, sharing neuropathological features. Melanoma Inhibitory Activity (MIA) was identified as a top cognitive decline predictor from blood plasma screens in PD patients. Although MIA was first isolated in metastatic melanoma in the central nervous system, it has not been studied in the context of neurodegeneration. As increased MIA expression was surprisingly only observed to associate with Aβ, whose principal association is with AD, and not ɑSyn, follow-up experiments focused on MIA’s potential role in shaping amyloid pathology. We generated amyloidogenic mice using the 5xFAD mouse model, varying the degree of endogenous MIA expression genetically in this model by crossing 5xFAD mice with MIA knockout (MIA-/-] animals to generate [5xFAD+/-; MIA+/+], [5xFAD+/-; MIA+/-], and [5xFAD+/-; MIA-/-] animals. It was found that decreasing MIA expression decreases Aβ plaque load, and decreasing MIA expression also increases Aβ plaque compaction metrics in amyloidogenic mice.