Trending with Impact: Treating Alzheimer’s Disease as a Systems Network Disorder



October 7, 2021

Aging-US published this trending research paper on September 21, 2020, entitled, “Alzheimer’s disease as a systems network disorder: chronic stress/dyshomeostasis, innate immunity, and genetics” by researchers from the Department of Neurology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA; Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA; Buck Institute for Research on Aging, Novato, CA. Abstract Ineffective results of clinical trials of over 200 anti-Alzheimer's drug candidates, with a 99.6% attrition rate, suggest that the current paradigm of Alzheimer's disease (AD) may be incomplete, necessitating exploration of alternative and complementary frameworks. Using algorithms for hypothesis independent search and expert-assisted synthesis of heterogeneous data, we attempted to reconcile multimodal clinical profiles of early-stage AD patients and accumulated research data within a parsimonious framework. Results of our analysis suggest that Alzheimer’s may not be a brain disease but a progressive system-level network disorder, which is driven by chronic network stress and dyshomeostasis. The latter can be caused by various endogenous and exogenous factors, such as chronic inflammatory conditions, infections, vascular dysfunction, head trauma, environmental toxicity, and immune disorders. Whether originating in the brain or on the periphery, chronic stress, toxicity, and inflammation are communicated to the central nervous system (CNS) via humoral and neural routes, preferentially targeting high-centrality regulatory nodes and circuits of the nervous system, and eventually manifesting as a neurodegenerative CNS disease. In this report, we outline an alternative perspective on AD as a systems network disorder and discuss biochemical and genetic evidence suggesting the central role of chronic tissue injury/dyshomeostasis, innate immune reactivity, and inflammation in the etiopathobiology of Alzheimer’s disease. Press release - Sign up for free Altmetric alerts about this article - DOI - Full text - Correspondence to: Alexei Kurakin email: and Dale E. Bredesen email: Keywords: Alzheimer’s disease, neurodegeneration, complex chronic disorder, network biology, systems biology About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at​​ or connect with us on: Twitter - Facebook - SoundCloud -​ YouTube -​ LinkedIn -​ Aging-US is published by Impact Journals, LLC please visit​​ or connect with @ImpactJrnls Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM


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