P1‐161: IMMUNOMODULATION: A PATH TO CEREBRAL AND RETINAL HOMEOSTASIS IN AN OLD, LATE‐STAGE MODEL OF ALZHEIMER'S DISEASE

• DOI: 10.1016/j.jalz.2019.06.716
• Publication Date: 2019-10-18T10:45:15Z
• Authors: Jonah Doustar; Giovanna C. Regis; Tania Torbati; Dieu-Trang Fuchs; Julia Sheyn; Altan Rentsendorj; Stuart Graham; Prediman K. Shah; Vivek K. Gupta; Keith L. Black; Mehdi Mirzaei; Yosef Koronyo; Maya Koronyo-Hamaoui
• Keywords: Astrocytosis; Entorhinal cortex

Previously, we have identified characteristic signs of Alzheimer's disease (AD) in the retina, a developmental outgrowth brain, presented as amyloid β-protein (Aβ) deposits. We further demonstrated feasibility non-invasive detection deposits retina and similar reduction cerebral retinal Aβ plaques response to immunomodulation young-adult APPSWE/PS1ΔE9 (ADtg) mice. However, exact relationship between brain pathology effects GA old mice, argued better correspond clinical human disease, not been previously investigated. Here, measured amyloidogenic non-amyloidogenic peptide concentrations both tissues aged, late-stage (21-24 months) ADtg mice immunotherapy. Sensitive biochemical MSD assays well immunohistochemistry mass spectrometry were applied assess quantify changes burden, astrocytosis synaptic biomarkers within tissues. Our data indicates strong direct correlations levels Aβ40 Aβ42 peptides, even at late stage. Similar responses immunotherapy also recorded these CNS Therapeutic on burden mostly localized entorhinal cortices. Additional assessment plaque phenotype revealed targeted large sized plaques, determined by their area, length width, dense-core aggregates. Importantly, GFAP was restricted following immunization all analyzed regions (hippocampus, cingulate cortex cortex). In-depth analysis astrocyte morphology functional showed restoration homeostatic glutamine synthetase (GS), an astrocyte-associated enzyme involved extracellular glutamate recycling, immunizations. Further, density aged indicated enhanced postsynaptic PSD95 biomarker expression areas reduced pathology. results illustrate efficacy immune-intervention, stages, portray first quantifiable method for determination, emphasizing potential predictive AD.