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A multiomic approach to characterize the temporal sequence in Alzheimer's disease-related pathology.

Abstract：

:No single-omic approach completely elucidates the multitude of alterations taking place in Alzheimer's disease (AD). Here, we coupled transcriptomic and phosphoproteomic approaches to determine the temporal sequence of changes in mRNA, protein, and phosphopeptide expression levels from human temporal cortical samples, with varying degree of AD-related pathology. This approach highlighted fluctuation in synaptic and mitochondrial function as the earliest pathological events in brain samples with AD-related pathology. Subsequently, increased expression of inflammation and extracellular matrix-associated gene products was observed. Interaction network assembly for the associated gene products, emphasized the complex interplay between these processes and the role of addressing post-translational modifications in the identification of key regulators. Additionally, we evaluate the use of decision trees and random forests in identifying potential biomarkers differentiating individuals with different degree of AD-related pathology. This multiomic and temporal sequence-based approach provides a better understanding of the sequence of events leading to AD.

journal_name

Neurobiol Dis

journal_title

Neurobiology of disease

authors

Marttinen M,Paananen J,Neme A,Mitra V,Takalo M,Natunen T,Paldanius KMA,Mäkinen P,Bremang M,Kurki MI,Rauramaa T,Leinonen V,Soininen H,Haapasalo A,Pike I,Hiltunen M

doi

10.1016/j.nbd.2018.12.009

subject

Has Abstract

pub_date

2019-04-01 00:00:00

pages

454-468

eissn

0969-9961

issn

1095-953X

pii

S0969-9961(18)30479-0

journal_volume

124

pub_type

杂志文章

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