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Published on: April 19, 2021
Detection of early proteomic alterations in 5xFAD Alzheimer's disease neonatal mouse model via MALDI-MSI
Irep Uras1, Merve Karayel-Basar1, Betul Sahin2
1Department of Biochemistry and Molecular Biology, Institute of Health Sciences, Acibadem Mehmet Ali Aydinlar University, Istanbul, Turkey.
Abstract:
Alzheimer's disease (AD) is a debilitating neurodegenerative disorder, characterized by memory deficit and dementia. AD is considered a multifactorial disorder where multiple processes like amyloid-beta and tau accumulation, axonal degeneration, synaptic plasticity, and autophagic processes plays an important role. In this study, the spatial proteomic differences in the neonatal 5xFAD brain tissue were investigated using MALDI-MSI coupled to LC-MS/MS, and the statistically significantly altered proteins were associated with AD. Thirty-five differentially expressed proteins (DEPs) between the brain tissues of neonatal 5xFAD and their littermate mice were detected via MALDI-MSI technique. Among the 35 proteins identified, 26 of them were directly associated with AD. Our results indicated a remarkable resemblance in the protein expression profiles of neonatal 5xFAD brain when compared to AD patient specimens or AD mouse models. These findings showed that the molecular alterations in the AD brain existed even at birth and that some proteins are neurodegenerative presages in neonatal AD brain. HIGHLIGHTS: Spatial proteomic alterations in the 5xFAD mouse brain compared to the littermate. 26 out of 35 differentially expressed proteins associated with Alzheimer's disease (AD). Molecular alterations and neurodegenerative presages in neonatal AD brain. Alterations in the synaptic function an early and common neurobiological thread.
Insights
Early molecular changes in Alzheimer's disease (AD) brains were identified in neonatal mice. These findings reveal neurodegenerative presages present at birth, offering new insights into AD pathogenesis.
Area of Science:
- Neuroscience
- Proteomics
- Alzheimer's Disease Research
Background:
- Alzheimer's disease (AD) is a progressive neurodegenerative disorder marked by memory loss and cognitive decline.
- It involves complex multifactorial processes including amyloid-beta and tau accumulation, axonal degeneration, and altered synaptic plasticity.
- Understanding early molecular changes is crucial for developing effective interventions.
Purpose of the Study:
- To investigate spatial proteomic differences in neonatal 5xFAD mouse brains.
- To identify early molecular alterations associated with Alzheimer's disease pathogenesis.
- To determine if molecular changes indicative of neurodegeneration are present at birth.
Main Methods:
- Utilized MALDI-MSI coupled with LC-MS/MS for spatial proteomic analysis.
- Compared protein expression profiles in neonatal 5xFAD mouse brains versus littermate controls.
- Statistically analyzed differentially expressed proteins (DEPs) for association with AD.
Main Results:
- Identified 35 differentially expressed proteins (DEPs) between neonatal 5xFAD and control mouse brains.
- Found that 26 out of 35 identified DEPs are directly associated with Alzheimer's disease.
- Observed significant resemblance between neonatal 5xFAD brain proteomic profiles and those in AD patient specimens or models.
Conclusions:
- Molecular alterations characteristic of Alzheimer's disease are present in the brain even at the neonatal stage.
- Certain proteins identified act as neurodegenerative presages in the neonatal AD brain.
- These findings highlight the potential for early detection and intervention strategies in AD.
