A Review of the Recent Advances in Alzheimer’s Disease Research and the Utilization of Network Biology Approaches for Prioritizing Diagnostics and Therapeutics

Abstract

Alzheimer’s disease (AD) is a polygenic multifactorial neurodegenerative disease that, after decades of research and development, is still without a cure. There are some symptomatic treatments to manage the psychological symptoms but none of these drugs can halt disease progression. Additionally, over the last few years, many anti-AD drugs failed in late stages of clinical trials and many hypotheses surfaced to explain these failures, including the lack of clear understanding of disease pathways and processes. Recently, different epigenetic factors have been implicated in AD pathogenesis; thus, they could serve as promising AD diagnostic biomarkers. Additionally, network biology approaches have been suggested as effective tools to study AD on the systems level and discover multi-target-directed ligands as novel treatments for AD. Herein, we provide a comprehensive review on Alzheimer’s disease pathophysiology to provide a better understanding of disease pathogenesis hypotheses and decipher the role of genetic and epigenetic factors in disease development and progression. We also provide an overview of disease biomarkers and drug targets and suggest network biology approaches as new tools for identifying novel biomarkers and drugs. We also posit that the application of machine learning and artificial intelligence to mining Alzheimer’s disease multi-omics data will facilitate drug and biomarker discovery efforts and lead to effective individualized anti-Alzheimer treatments.

The Role of microRNAs in Epigenetic Regulation of Signaling Pathways in Neurological Pathologies

“…According to several authors, RNA interference mediated by microRNAs can initiate neurovascular events leading to Alzheimer’s-type neurodegeneration [ 90 , 91 , 92 , 93 ]. This provides a strong theoretical basis for the development of new directions in targeted genetic therapy for neurodegenerative diseases [ 94 , 95 , 96 , 97 ].…”

Novel histone post-translational modifications in Alzheimer’s disease: current advances and implications

“…Alzheimer's disease (AD), a degenerative disease of the central nervous system, is characterized by progressive cognitive and behavioral impairment, and it primarily occurs in the elderly and pre-elderly [1]. The incidence, prevalence, mortality, and morbidity rates of AD are not optimistic [2].…”

“…Multiple-related mechanisms contribute to the pathogenesis of AD, including interconnected networks of genetic, epigenetic, biological, and environment factors [3]. Deposition of misfolded amyloid beta (Aβ) peptides and the microtubule-associated protein tau are important pathological features of AD [1,4]. Neuroinflammation and the activation and action of innate immune cells are also involved in the pathophysiological mechanisms of AD [5].…”

Microorganism-Derived Molecules as Enzyme Inhibitors to Target Alzheimer’s Diseases Pathways

“…Alzheimer's disease (AD) is a multifactorial disease featured by the deposition of amyloid-beta (Aβ) plaques and neurofibrillary tangles in the brain, leading to the death of neuronal cells and memory loss [1,2]. AD increases the risk of other serious diseases and has a great impact on individuals, families, and socioeconomics [3].…”