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

Harald Hampel 1 Nicola Toschi 2 Claudio Babiloni 3 Filippo Baldacci 4 Keith Black 5 Arun Bokde 6 René Bun 7 Francesco Cacciola 8 Enrica Cavedo 7 Patrizia Chiesa 7 Olivier Colliot 9 Cristina-Maria Coman 7 Bruno Dubois 7, 10 Andrea Duggento 2 Stanley Durrleman 9 Maria-Teresa Ferretti 11 Nathalie George 10 Rémy Genthon 12 Marie-Odile Habert 10 Karl Herholz 13 Yosef Koronyo 5 Maya Koronyo-Hamaoui 5 Foudil Lamari 14 Todd Langevin 15 Stéphane Lehéricy 16 Jean Lorenceau 17 Christian Néri 7 Robert Nisticò 2 Francis Nyasse 7, 10 Craig Ritchie 18 Simone Rossi 19 Emiliano Santarnecchi 19 Olaf Sporns 20 Steven Verdooner 21 Andrea Vergallo 7, 10 Nicolas Villain 22 Erfan Younesi 23 Francesco Garaci 24 Simone Lista 1 Arun L.W. Bokde 6
Abstract : The Precision Neurology development process implements systems theory with system biology and 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 research path is paralleled by an “omics”-based, hypothesis-free, exploratory research pathway, 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 marker signatures 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 endophenotypes and 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 nature of aging individuals. The APMI movement is gaining momentum to systematically apply both systems neurophysiology and systems biology in exploratory translational neuroscience research on ND.
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Harald Hampel, Nicola Toschi, Claudio Babiloni, Filippo Baldacci, Keith Black, et al.. Revolution of Alzheimer Precision Neurology. Passageway of Systems Biology and Neurophysiology. Journal of Alzheimer's Disease, IOS Press, 2018, 64 (s1), pp.S47 - S105. ⟨10.3233/jad-179932⟩. ⟨hal-01910402⟩

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