An integrative proteomic approach during Alzheimer’s disease progression in Tau PS19 mice

ABSTRACT: 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 hyperphosphorylated tau protein. AD is associated with the dysfunction of several essential neurotransmitter systems, such as dopamine, and individuals with AD have been shown to have impaired neurotransmission. Although neurotransmitter changes in the brain are associated with AD pathology, in-depth profiling studies on neurotransmitters and their related proteomic changes need to be conducted. Thus, we conducted a study to profile and integrate the proteomes and neurotransmitters in seven brain regions of PS19 (Tau P301S) mice according to AD progression between 4-month and 7-month. Proteomic analysis revealed significantly altered canonical pathways in various brain regions, including metabolic abnormalities. In the neurotransmitter profile, we found that six neurotransmitters, dopamine, serotonin, homovanillic acid, norepinephrine, 3-methoxytyramine, and 3,4-dihydroxyphenylacetic acid, were significantly altered during AD progression. Using an integrative approach between proteome and neurotransmitter profiles, we found that AD progression-dependent dopamine- and serotonin-related signaling modules are closely related to neurotransmitter changes, especially in the hippocampus and cerebellum. This integrative approach could provide new signaling modules to help understand the progression of AD.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

SUBMITTER: Eunji Cho  

LAB HEAD: Jong Hyuk Yoon

PROVIDER: PXD066515 | Pride | 2026-06-15

REPOSITORIES: Pride