Amyloid Deposition and Inflammation in APPswe/PS1dE9 Mouse Model of Alzheimers Disease

Lingfei      Ruan; Zhoujun      Kang; Gang      Pei; Yingying      Le

Abstract

Alzheimers disease (AD) is characterized by amyloid plaques and neurofibrillary tangles associated with chronic inflammation. APPswe/PS1dE9 is an AD mouse model bearing mutant transgenes of amyloid precursor protein and presenilin-1. Amyloid deposition is present in this mouse model at early stage of life. However, the progression of inflammation and its relationship with amyloid deposition have not been characterized. Here we showed that amyloid plaques were present at 4 months of age and increased with age. CD11b-positive microglia clusters appeared in hippocampus and neocortex at 4 months of age and increased with age. Clustered glial fibrillary acidic protein (GFAP)-positive astrocytes were observed in hippocampus and cortex after 6 months of age and increased with age. Double staining with CD11b/GFAP antibody and thioflavin S showed clustered microglia and astrocytes were in close association with amyloid plaques. Expression of TNF-α was detected at 8 months of age, while IL-1β, IL-6 and MCP-1 at 10 months. These cytokines increased with age. Double immunostaining of cell specific marker and cytokine indicated TNF-α, IL-1β, IL-6 and MCP-1 were expressed by activated microglia and a small part of activated astrocytes. MCP-1 was also expressed by neurons, which support recent finding that MCP-1 expression was increased in neurons of AD patient. These results demonstrate amyloid plaques and its associated inflammatory response developed at early stage of life and progressively increased with age, both activated glia and neurons are involved in chronic inflammation in AD. APPswe/PS1dE9 model provides a mean for studying the mechanisms and novel therapeutics for AD.

Keywords: Alzheimer's disease, APPswe/PS1dE9, transgenic mouse, amyloid deposition, inflammation, microglia, astrocyte, neuron