Revolution of Alzheimer Precision Neurology. Passageway of Systems Biology and Neurophysiology

The Precision Neurology development process implements systems theory with system biologyand neurophysiology in a parallel, bidirectional research path: a combined hypothesis-driven investigation of systems dysfunction within distinct molecular, cellular, and large-scale neural network systems in both animal models as well as through tests for the usefulness of these candidate dynamic systems biomarkers in different diseases and subgroups at different stages of pathophysiological progression. This translational researchpath is paralleled by an “omics”-based, hypothesis-free, exploratory researchpathway, which will collect multimodal data from progressing asymptomatic, preclinical, and clinical neurodegenerative disease (ND) populations, within the wide continuous biological and clinical spectrum of ND, applying high-throughput and high-content technologies combined with powerful computational and statistical modeling tools, aimed at identifying novel dysfunctional systems and predictive markersignatures associated with ND. The goals are to identify common biological denominators or differentiating classifiers across the continuum of ND during detectable stages of pathophysiological progression, characterize systems-based intermediate endophenotypes, validate multi-modal novel diagnostic systems biomarkers, and advance clinical intervention trial designs by utilizing systems-based intermediate endophenotypesand candidate surrogate markers. Achieving these goals is key to the ultimate development of early and effective individualized treatment of ND, such as Alzheimer’s disease. The Alzheimer Precision Medicine Initiative(APMI) and cohort program (APMI-CP), as well as the Paris based core of the Sorbonne University Clinical Research Group “Alzheimer Precision Medicine” (GRC-APM) were recently launched to facilitate the passageway from conventional clinical diagnostic and drug development toward breakthrough innovation based on the investigation of the comprehensive biological natureof aging individuals. The APMI movement is gaining momentum to systematically apply both systems neurophysiology and systems biologyin exploratory translational neuroscience research on ND.