P2‐191: TWO DECADES OF RESEARCH USING POSTMORTEM HUMAN MICROGLIA: FINDINGS AND EXPERIENCES FROM BANNER SUN HEALTH RESEARCH INSTITUTE RAPID AUTOPSY PROGRAM

Background: Human microglia isolated from postmortem elderly brains are diseaseand age-appropriate cellular models for aging and neurodegenerative disease research. In the last two decades, we have routinely used brain tissues autopsied by the Brain and Body Donation Program (www. brainandbodydonationprogram.org) to isolate microglia for neuroinflammatory mechanism modeling. Human research subjects are derived from the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND) and Arizona Alzheimer’s Consortium. The BBDP autopsy cases provide brain tissues from non-demented controls and neurodegenerative diseases with mean age of 84 years and postmortem delays routinely under 3.5 hours. Tissue donors receive annual and extensive behavioral neurology, movement neurology and neuropsychological assessments (Beach et al., 2008, 2015). We highlight the findings from our past and ongoing human microglia research to provide the rationale for launching a new initiative to bank human microglia cells as a shared resource at the BBDP-BSHRI. Methods: The postmortem microglia isolation procedures have been described in our previous publications. The procedures were initially focusing on microglia using trypsin as dissociation enzyme during 1996-2006, then revised for simultaneous isolation of microglia and vascular cells including smooth muscle cells, pericytes, and blood-brain barrier microvascular endothelial cells using papain as dissociation enzyme. Results: We have characterized the postmortem human microglia through studies in the expression and mechanisms of the receptors and signaling molecules involved in biological functions of the microglia; (1) inflammation-associated receptors; examples: the receptor for colony stimulating factor-1 receptor (2018), Toll-like receptor family (2017), urokinase plasminogen-activator receptor (2002), Fc gamma receptors (2002), and receptor for advanced glycation end-products (RAGE) (2001); and (2) the inflammation-regulatory signaling mechanisms; examples: CD33 (2016), Suppressor of Cytokine Signaling Genes (2015), and CD200 receptor (2009). Using gene microarray and RNA-seq, human elderly microglia showed a broad spectrum of up-and down-regulated gene expressions in response to chronic and/or acute stimulations of amyloid b (2006) and IL34 and CSF-1 (2018). Conclusions: Our extensive experience and publication record indicate that postmortem microglia derived from human elderly brains are a robust cellular model and justify the banking of these cells as a shared resource for aging and neurodegenerative research. P2-192 PROTECTIVE EFFECTS OF ESTRADIOL ON METABOLIC AND NEURAL EFFECTS OF OBESITY IN FEMALE APOE3 AND APOE4 MICE AT EARLY MIDDLE AGE