Detection of early proteomic alterations in 5xFAD Alzheimer's disease neonatal mouse model via MALDI‐MSI

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.

Detection of proteomic alterations at different stages in a Huntington's disease mouse model via matrix‐assisted laser desorption/ionization mass spectrometry (MALDI‐MS) imaging

“…The experimental workflow from tissue preparation until MSI analyses and MALDI MSI data acquisition is presented in great detail in our previous studies (Karayel-Basar et al, 2022;Uras et al, 2023). Sample preparations for MALDI-MSI analysis were done using that presented protocol, with minor modifications.…”

“…To interpret our MALDI-MSI data, we performed the unsupervised segmentation analysis in SciLS Lab software (Version 2016b, SCiLS GmbH, https://scils.de), as mentioned in detail in our previous studies (Karayel-Basar et al, 2022;Uras et al, 2023). Briefly, the following parameters were applied with minor changes: importing MALDI data into SciLS Lab, preprocessing individually by convolution baseline removal and TIC normalisation, ±0.156 Da interval width, medium smoothing strength and maximum interval processing.…”

Sex differences in the relationship between depression and Alzheimer’s disease—mechanisms, genetics, and therapeutic opportunities

“…Alzheimer’s disease (AD) is a leading neurodegenerative disorder, characterized by cognitive deficits, behavioral changes, and memory loss ( Nebel et al, 2018 ; Depp et al, 2023 ). Recognized as a multifactorial disorder with diverse etiologies ( Guo et al, 2022 ; Uras et al, 2023 ), emerging evidence highlights sex differences as a significant contributor to AD’s heterogeneity, influencing prevalence, disease progression, risk factors, and outcomes ( Tremblay et al, 2023 ). Women, who represent about two-thirds of AD patients, exhibit a faster cognitive decline and higher susceptibility to AD ( Hampel et al, 2018 ; Levine et al, 2021 ; Martinkova et al, 2021 ; Cui et al, 2023 ).…”