Comparative analyses of ex vivo inflammatory microglial responses from human adult Alzheimer’s Disease and control subjects

The hallmark of Alzheimer’s Disease (AD) is the formation of neuritic plaques composed of β‐amyloid (Aβ) aggregates surrounded by activated glia, which secrete inflammatory mediators. To examine inflammatory responses, microglia were isolated from post‐mortem AD and age‐matched non‐demented (ND) brain tissue. Naïve production of TNF‐α from AD microglia was significantly lower than ND at 6h and not significantly different at 24h post media exchange. Microglia were stimulated for 6h and 24h with CD40 ligand (CD40L), interferon‐γ (IFN‐γ), and interleukin‐1β (IL‐1 β) in the absence and presence of Aβ 1–42 and levels of TNF‐α were determined. When activated with CD40L, IFN‐γ or IL‐1β, both AD and ND microglia secreted comparable levels of TNF‐α. In the presence of Aβ, AD microglia produced 50‐fold greater TNF‐α than ND cells at 6h and 2‐fold higher at 24h. When activated with CD40L, IFN‐γ, or IL‐1β with Aβ, TNF‐α production was downregulated in AD and upegulated in ND when compared to Aβ. These data investigate the effects of in vivo disease on microglia responses providing insight into the role of microglia in disease mechanisms. Research support: Univ. of NE Med. Ctr. Clin. Rsrch. Ctr., UNMC and NIH PO1 NF35432[core].