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Amyloid β (Aβ) accumulates in Alzheimer's disease (AD) brain. Microglial activation also occurs in AD, and this inflammatory response may contribute to disease progression. Microglial activation can be induced by Aβ, but the mechanisms by which this occurs have not been defined. The nuclear enzyme poly(ADP-ribose) polymerase-1 (PARP-1) regulates microglial activation in response to several stimuli through its interactions with the transcription factor, NF-κB. The purpose of this study was to evaluate whether PARP-1 activation is involved in Aβ-induced microglial activation, and whether PARP-1 inhibition can modify microglial responses to Aβ.

hAPP_J20 mice, which accumulate Aβ with ageing, were crossed with PARP-1^-/- mice to assess the effects of PARP-1 depletion on microglial activation, hippocampal synaptic integrity …