Abstract
Alzheimer's disease (AD) is a chronic neurodegenerative disorder that involves strong inflammatory components. Aberrant and prolonged inflammation in the CNS is thought to contribute to the development of the pathology. The use of single cytokine approaches to curb or leverage inflammatory mechanisms for disease modifying benefit has often resulted in conflicting data. Furthermore, these treatments were usually delivered locally into the CNS parenchyma, complicating translational efforts. To overcome these hurdles, we tested the use of glatiramer acetate (GA) in reducing amyloid beta (Aβ) plaque pathology in the 5xFAD model of AD. GA immunizations were begun at the ages of 2.5 months, 5.5 months, and 8.5 months, and GA was delivered weekly for 8 weeks. While previous data describe potential benefits of GA immunization in decreasing Aβ levels in murine models of AD, we found modest decreases in Aβ levels if given during the development of pathology but, surprisingly, found increased Aβ levels if GA was administered at later stages. The impact of GA treatment was only significant for female mice. Furthermore, we observed no changes between microglial uptake of plaque, CD11c immunopositivity of microglia, or levels of TMEM119 and P2Ry12 on microglia. Overall, these data warrant exercising caution when aiming to repurpose GA for AD.