Neurodegenerative diseases such as Alzheimer’s disease (AD) are multifactorial involving genomics, metabolomics, epigenomics, transcriptomics, interactomics, as well as environmental components. Systemic understanding of these complex diseases may start with the alterations in the cellular networks. Investigation in integrative systems biology at various ‘omics’ levels may help understand the disease onset and progression for prevention at early stages.

For example, microRNAs (miRNAs) are critical in the regulation of mRNA complexity in the central nervous system (CNS) (Roth et al., 2016). They are involved in the management of gene expression profiles in a spatiotemporal way. Such activities are important in the neuronal plasticity and aging, as well as age-associated neurodegeneration such as Alzheimer’s disease (AD).

In AD, the key risk factors include genomic susceptibility, abnormal central amyloid precursor protein (APP) activities, and tau networks (Castrillo and Oliver, 2016). The dysfunction of these networks may lead to higher levels of toxic species and the loss of the balances.

Studies have also identified miRNAs and miRNA networks associated with APP splicing and processing, tau and its cellular subnetworks, as well as Aβ pathology (Roth et al., 2016). These mechanisms are crucial in the onset and progression of Alzheimer’s disease.


Castrillo JI, Oliver SG. Alzheimer’s as a Systems-Level Disease Involving the Interplay of Multiple Cellular Networks. Methods Mol Biol. 2016;1303:3-48. doi:

Roth W, Hecker D, Fava E. Systems Biology Approaches to the Study of Biological Networks Underlying Alzheimer’s Disease: Role of miRNAs. Methods Mol Biol. 2016;1303:349-77. doi: 10.1007/978-1-4939-2627-5_21.

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