Alz Res Therapy: Integrating multiple omics, revealing pathway changes in the nervous system

In addition to amyloid pathology and tau-related neurodegeneration, there are many other molecular changes and pathway disorders in Alzheimer's disease (AD)

However, the contribution and relevance of these changes to the clinical manifestations and progression of the disease, as well as their inter-individual differences and complex interrelationships, are still poorly understood

Although these processes are not generally considered part of the "core" pathology of AD, they may contribute greatly to the development of amyloid pathology and neurodegeneration, and promote the manifestation of symptoms

In the past ten years, "omics" methods and techniques have made significant progress in solving the complexity of metabolome, lipidome and proteome

Recent statistics Advances in the information integration of multiple data models become possible to thoroughly explore the connotation of networks and disease-related biological interactions

In this way, Christopher Clark and others of the Zurich University Hospital hypothesized that the specific patterns of proteins, lipids, neuroinflammatory markers, and metabolites are related to the core characteristics of AD pathology, and indicated that the changes in disease-related and interconnected biological pathways

They conducted a multi-level cerebrospinal fluid (CSF) comprehensive analysis of the elderly with obvious characteristics of normal cognition, mild cognitive impairment, and mild dementia

Multi-omics integration identified five main heterogeneity dimensions, explained the differences in the cohort, and had different associations with AD

The analysis of abundant pathways shows that the proportion of homeostasis, immune response and extracellular matrix signaling pathways related to AD is too high

Finally, the combination of the four molecules improves AD (protein 14-3-3 zeta/delta, clusterin, interleukin-15 and transgelin-2) and cognitive decline (protein 14-3-3 zeta/delta, Clusterin, cholesteryl ester 27:1 16:0 and monocyte chelating protein-1) prediction

The important significance of this research lies in the discovery of new molecules and pathway changes related to AD pathology