title: PRECISION MEDICINE - The Golden Gate for Detection, Treatment and Prevention of Alzheimer's Disease.
abstract: During this decade, breakthrough conceptual shifts have commenced to emerge in the field of Alzheimer's disease (AD) recognizing risk factors and the non-linear dynamic continuum of complex pathophysiologies amongst a wide dimensional spectrum of multi-factorial brain proteinopathies/neurodegenerative diseases. As is the case in most fields of medicine, substantial advancements in detecting, treating and preventing AD will likely evolve from the generation and implementation of a systematic precision medicine strategy. This approach will likely be based on the success found from more advanced research fields, such as oncology. Precision medicine will require integration and transfertilization across fragmented specialities of medicine and direct reintegration of Neuroscience, Neurology and Psychiatry into a continuum of medical sciences away from the silo approach. Precision medicine is biomarker-guided medicine on systems-levels that takes into account methodological advancements and discoveries of the comprehensive pathophysiological profiles of complex multi-factorial neurodegenerative diseases, such as late-onset sporadic AD. This will allow identifying and characterizing the disease processes at the asymptomatic preclinical stage, where pathophysiological and topographical abnormalities precede overt clinical symptoms by many years to decades. In this respect, the uncharted territory of the AD preclinical stage has become a major research challenge as the field postulates that early biomarker guided customized interventions may offer the best chance of therapeutic success. Clarification and practical operationalization is needed for comprehensive dissection and classification of interacting and converging disease mechanisms, description of genomic and epigenetic drivers, natural history trajectories through space and time, surrogate biomarkers and indicators of risk and progression, as well as considerations about the regulatory, ethical, political and societal consequences of early detection at asymptomatic stages. In this scenario, the integrated roles of genome sequencing, investigations of comprehensive fluid-based biomarkers and multimodal neuroimaging will be of key importance for the identification of distinct molecular mechanisms and signaling pathways in subsets of asymptomatic people at greatest risk for progression to clinical milestones due to those specific pathways. The precision medicine strategy facilitates a paradigm shift in Neuroscience and AD research and development away from the classical "one-size-fits-all" approach in drug discovery towards biomarker guided "molecularly" tailored therapy for truly effective treatment and prevention options. After the long and winding decade of failed therapy trials progress towards the holistic systems-based strategy of precision medicine may finally turn into the new age of scientific and medical success curbing the global AD epidemic.
authors.affiliation: AXA Research Fund & UPMC Chair, Paris, France; Sorbonne Universities, Pierre and Marie Curie University, Paris 06, Institute of Memory and Alzheimer's Disease (IM2A) & Brain and Spine Institute (ICM) UMR S 1127, Department of Neurology, Pitié-Salpêtrière University Hospital, Paris, France.
authors.forename: H
authors.initials: H
authors.lastname: Hampel
authors.affiliation: Institute for Healthy Aging, University of North Texas Health Science Center, Fort Worth, TX USA.
authors.forename: S E
authors.initials: SE
authors.lastname: O'Bryant
authors.affiliation: Genetadi Biotech S.L. Parque Tecnológico de Bizkaia, Derio, Bizkaia, Spain.
authors.forename: J I
authors.initials: JI
authors.lastname: Castrillo
authors.affiliation: Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.
authors.forename: C
authors.initials: C
authors.lastname: Ritchie
authors.affiliation: AXA Research Fund & UPMC Chair, Paris, France; Sorbonne Universities, Pierre and Marie Curie University, Paris 06, Institute of Memory and Alzheimer's Disease (IM2A) & Brain and Spine Institute (ICM) UMR S 1127, Department of Neurology, Pitié-Salpêtrière University Hospital, Paris, France.
authors.forename: K
authors.initials: K
authors.lastname: Rojkova
authors.affiliation: President, Federal Institute for Drugs and Medical Devices (BfArM), Bonn, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Broich
authors.affiliation: Biostatistics and Special Pharmacokinetics Unit/Research Division, Federal Institute for Drugs and Medical Devices (BfArM), Bonn, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Benda
authors.affiliation: Department of Biology, University of Rome "Tor Vergata" & Pharmacology of Synaptic Disease Lab, European Brain Research Institute (E.B.R.I.), Rome, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Nisticò
authors.affiliation: Siemens Healthineers North America, Siemens Medical Solutions USA, Inc, Malvern, PA, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Frank
authors.affiliation: AXA Research Fund & UPMC Chair, Paris, France; Sorbonne Universities, Pierre and Marie Curie University, Paris 06, Institute of Memory and Alzheimer's Disease (IM2A) & Brain and Spine Institute (ICM) UMR S 1127, Department of Neurology, Pitié-Salpêtrière University Hospital, Paris, France.
authors.forename: B
authors.initials: B
authors.lastname: Dubois
authors.affiliation: Medical Research Council (MRC) Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, Wales, UK.
authors.forename: V
authors.initials: V
authors.lastname: Escott-Price
authors.affiliation: AXA Research Fund & UPMC Chair, Paris, France; IHU-A-ICM - Paris Institute of Translational Neurosciences, Pitié-Salpêtrière University Hospital, Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Lista
keywords: Alzheimer’s disease; biomarkers; precision medicine; precision medicine initiative; systems biology