Integrative proteomics approach for AD progression in PS19 model mice reveals new signaling modules

초록

Alzheimer's disease (AD) is a progressive neurodegenerative disease associated with cognitive, functional, and behavioral impairments. It is characterized by the accumulation of extracellular amyloid-β plaques, and formation of intracellular neurofibrillary tangles by accumulating hyperphosphorylated-tau protein. Changes in neurotransmitter function, such as dopamine, are also significant in AD, leading to impaired neurotransmission. While the association between neurotransmitter alteration and AD pathology is recognized, indepth profiling about neurotransmitters and their related proteomic changes still needs to be studied. Thus, we conducted a study to profile and integrate proteomes and neurotransmitters using seven brain regions of PS19 (Tau P301S) mice according to AD progression. We found notable changes in canonical pathways, including metabolic abnormalities, depending on the brain regions though proteomic analysis. Additionally, alteration of six neurotransmitters were identified under AD progression via profiling neurotransmitters. By integrating the proteomic and neurotransmitters profiles, we found that several specific neurotransmitter-related signaling modules are AD progression-dependently associated to the neurotransmitter changes, especially in the hippocampus and cerebellum. This integrative approach could offer new signaling modules to help understand AD progression.