Network Approaches to the Understanding of Alzheimer’s Disease: From Model Organisms to Humans

Yerbury, Justin J.; Bean, Daniel; Favrin, Giorgio

doi:10.1007/978-1-4939-2627-5_27

Cited by 3 publications

(1 citation statement)

References 45 publications

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“…However, most such studies are based on brain/postmortem samples and are thus not suitable for noninvasisve diagnosis and DMTs. Concluding, despite the wider use of systems-level approaches in complex neurodegenerative diseases [43], [44], approaches extracting network-based biomarkers in AD using omics data from blood samples are still in their infancy, though considered as the emerging paradigm in AD prognosis and early diagnosis [45].…”

Section: Emerging Approaches: Network-based Biomarkersmentioning

confidence: 99%

A Network-Based Perspective in Alzheimer's Disease: Current State and an Integrative Framework

Dragomir

Vrahatis

Bezerianos

2019

IEEE J. Biomed. Health Inform.

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A major rise in the prevalence and impact of Alzheimer's Disease (AD) is projected in the coming decades, resulting from increasing life expectancy, thus leading to substantially increased healthcare costs. While brain disfunctions at the time of diagnosis are irreversible, it is widely accepted that AD pathology develops decades before clinical symptoms onset. If incipient processes can be detected early in the disease progression, prospective intervention for preventing or slowing the disease can be designed. Currently, there is no noninvasive biomarker available to detect and monitor early stages of disease progression. The complex etiology of AD warrants a systems-based approach supporting integration of multimodal and multilevel data, while network-based modeling provides the scaffolding for methods revealing complex systems-level disruptions initiated by the disease. In this work we review current state-of-the-art, focusing on network-based biomarkers at molecular and brain functional connectivity levels. Particular emphasis is placed on outlining recent trends which highlight the functional importance of modular substructures in molecular and connectivity networks and their potential biomarker value. Our perspective is rooted in network medicine and summarizes the pipelines for identifying network-based biomarkers, as well as the benefits of integrating genotype and brain phenotype information for a comprehensively noninvasive approach in early diagnosis of AD. Finally, we propose a framework for integrating knowledge from molecular and brain connectivity levels which has the potential to enable noninvasive diagnosis, provide support for monitoring therapies, and help understand heretofore unexamined deep level relations between genotype and brain phenotype.

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Section: Emerging Approaches: Network-based Biomarkersmentioning

confidence: 99%

A Network-Based Perspective in Alzheimer's Disease: Current State and an Integrative Framework

Dragomir

Vrahatis

Bezerianos

2019

IEEE J. Biomed. Health Inform.

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Systems Biology Methods for Alzheimer’s Disease Research Toward Molecular Signatures, Subtypes, and Stages and Precision Medicine: Application in Cohort Studies and Trials

Castrillo

Lista

Hampel

et al. 2018

Biomarkers for Alzheimer’s Disease Drug Development

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Alzheimer's disease (AD) is a complex multifactorial disease, involving a combination of genomic, interactome, and environmental factors, with essential participation of (a) intrinsic genomic susceptibility and (b) a constant dynamic interplay between impaired pathways and central homeostatic networks of nerve cells. The proper investigation of the complexity of AD requires new holistic systems-level approaches, at both the experimental and computational level. Systems biology methods offer the potential to unveil new fundamental insights, basic mechanisms, and networks and their interplay. These may lead to the characterization of mechanism-based molecular signatures, and AD hallmarks at the earliest molecular and cellular levels (and beyond), for characterization of AD subtypes and stages, toward targeted interventions according to the evolving precision medicine paradigm. In this work, an update on advanced systems biology methods and strategies for holistic studies of multifactorial diseases-particularly AD-is presented. This includes next-generation genomics, neuroimaging and multi-omics methods, experimental and computational approaches, relevant disease models, and latest genome editing and single-cell technologies. Their progressive incorporation into basic research, cohort studies, and trials is beginning to provide novel insights into AD essential mechanisms, molecular signatures, and markers toward mechanism-based classification and staging, and tailored interventions. Selected methods which can be applied in cohort studies and trials, with the European Prevention of Alzheimer's Dementia (EPAD) project as a reference example, are presented and discussed.

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Proteome Homeostasis Dysfunction: A Unifying Principle in ALS Pathogenesis

Yerbury

Farrawell

McAlary

2020

Trends in Neurosciences

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Network Approaches to the Understanding of Alzheimer’s Disease: From Model Organisms to Humans

Cited by 3 publications

References 45 publications

A Network-Based Perspective in Alzheimer's Disease: Current State and an Integrative Framework

A Network-Based Perspective in Alzheimer's Disease: Current State and an Integrative Framework

Systems Biology Methods for Alzheimer’s Disease Research Toward Molecular Signatures, Subtypes, and Stages and Precision Medicine: Application in Cohort Studies and Trials

Proteome Homeostasis Dysfunction: A Unifying Principle in ALS Pathogenesis

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