Acute systemic inflammation exacerbates neuroinflammation in Alzheimer's disease: IL‐1β drives amplified responses in primed astrocytes and neuronal network dysfunction

• DOI: 10.1002/alz.12341
• Publication Date: 2021-06-04T09:33:27Z
• Authors: Ana Belen Lopez‐R...; Edel Hennessy; Carol L. Murray; Arshed Nazmi; Hugh J. Delaney; Dáire Healy; Steven G. Fagan; Michael Rooney; Erika Stewart; Anouchka Lewis; Niamh de Barra; Philip Scarry; Louise Riggs‐Miller; Delphine Boche; Mark O. Cunningham; Colm Cunningham
• Keywords: 0301 basic medicine; 570; Amyloid; Inflammasomes; Interleukin-1beta; IL-1β disrupted hippocampal gamma rhythm; Vulnerability; Alzheimer’s disease (AD); Mice, Transgenic; Network dysfunction; Hippocampus; Mice; 03 medical and health sciences; Neuroinflammation; Memory; Alzheimer Disease; 616; Animals; Humans; Gamma; Cytokine; APP/PS1; Inflammation; Neurons; trigger delirium; Delirium; Brain; 3. Good health; IL-1β; Chemokine; Priming; Astrocytes; Cytokines; Dementia; Microglia; Primed; Astrocyte; CCL2

Neuroinflammation contributes to Alzheimer's disease (AD) progression. Secondary inflammatory insults trigger delirium and can accelerate cognitive decline. Individual cellular contributors this vulnerability require elucidation. Using APP/PS1 mice AD brain, we studied secondary investigate hypersensitive responses in microglia, astrocytes, neurons, human brain tissue. The NLRP3 inflammasome was assembled surrounding amyloid beta, microglia were primed, facilitating exaggerated interleukin-1β (IL-1β) subsequent LPS stimulation. Astrocytes primed produce chemokine intrahippocampal IL-1β. Systemic triggered microglial IL-1β, astrocytic chemokines, IL-6, acute dysfunction, whereas IL-1β disrupted hippocampal gamma rhythm, all selectively mice. Brains from patients with infection showed elevated IL-6 levels. Therefore, leaves the vulnerable inflammation at microglial, astrocytic, neuronal, levels, amplifies neuroinflammatory cytokine synthesis humans. Exacerbation of neuroinflammation deleterious outcomes like accelerated progression merits careful investigation