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Department of Neuroscience, Baylor College of Medicine, Houston, TX, 77030, USA, Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX, USA
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A causal chain linking AD pathology, transcriptome perturbation, N-Methyl-D-Aspartate receptor excitotoxicity, and neurodegeneration is established, establishing a biphasic model in which early AD pathology activation of a synaptic transcriptional signature that promotes neuronal injury, followed by a decrease that is compensatory.