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

초록

Alzheimer's disease (AD) is a slowly progressive neurodegenerative disease associated with cognitive, functional, and behavioral impairments characterized by the progressive accumulation of extracellular amyloid beta plaques and intracellular neurofibrillary tangles of the accumulation of hyperphosphorylated-tau protein. It is associated with dysfunction in several essential neurotransmitter systems, such as dopamine, and individuals with AD have been shown to have impaired neurotransmission. While neurotransmitter changes in the brain have been associated with AD pathology, in-depth profiling studies on neurotransmitters and their related proteomic changes still need to be studied. Thus, we conducted a study to profile and integrate proteomes and neurotransmitters of seven brain regions of PS19 (Tau P301S) mice according to AD progression. We found significantly changed canonical pathways in the brain regions in proteomic analysis, including metabolic abnormalities. In the profile of neurotransmitters, we found that six neurotransmitters were significantly changed under AD progression. By integrative approach between profiles of proteome and neurotransmitters, we found AD progression-dependent several specific neurotransmitter-related signaling modules are closely related to the neurotransmitter changes, especially in the hippocampus and cerebellum. This integrative approach could provide new signaling modules to help understand AD progression.