title: A Precision Medicine Initiative for Alzheimer's disease: the road ahead to biomarker-guided integrative disease modeling.
abstract: After intense scientific exploration and more than a decade of failed trials, Alzheimer's disease (AD) remains a fatal global epidemic. A traditional research and drug development paradigm continues to target heterogeneous late-stage clinically phenotyped patients with single 'magic bullet' drugs. Here, we propose that it is time for a paradigm shift towards the implementation of precision medicine (PM) for enhanced risk screening, detection, treatment, and prevention of AD. The overarching structure of how PM for AD can be achieved will be provided through the convergence of breakthrough technological advances, including big data science, systems biology, genomic sequencing, blood-based biomarkers, integrated disease modeling and P4 medicine. It is hypothesized that deconstructing AD into multiple genetic and biological subsets existing within this heterogeneous target population will provide an effective PM strategy for treating individual patients with the specific agent(s) that are likely to work best based on the specific individual biological make-up. The Alzheimer's Precision Medicine Initiative (APMI) is an international collaboration of leading interdisciplinary clinicians and scientists devoted towards the implementation of PM in Neurology, Psychiatry and Neuroscience. It is hypothesized that successful realization of PM in AD and other neurodegenerative diseases will result in breakthrough therapies, such as in oncology, with optimized safety profiles, better responder rates and treatment responses, particularly through biomarker-guided early preclinical disease-stage clinical trials.
authors.affiliation: a AXA Research Fund & UPMC Chair , Paris , France.|b Département de Neurologie , Sorbonne Universités, Université Pierre et Marie Curie (UPMC), Paris 06, Inserm, CNRS, Institut du cerveau et de la moelle (ICM), Institut de la Mémoire et de la Maladie d'Alzheimer (IM2A), Hôpital Pitié-Salpêtrière, Boulevard de l'hôpital , Paris , France.
authors.forename: H
authors.initials: H
authors.lastname: Hampel
authors.affiliation: c 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: d ARAMIS Lab, Inria Paris , Paris , France.|e Sorbonne Universités, UPMC Univ Paris 06, Inserm, CNRS, Institut du cerveau et la moelle (ICM), Hôpital Pitié-Salpêtrière, Boulevard de l'hôpital , Paris , France.
authors.forename: S
authors.initials: S
authors.lastname: Durrleman
authors.affiliation: f European Society for Translational Medicine , Vienna , Austria.
authors.forename: E
authors.initials: E
authors.lastname: Younesi
authors.affiliation: a AXA Research Fund & UPMC Chair , Paris , France.|b Département de Neurologie , Sorbonne Universités, Université Pierre et Marie Curie (UPMC), Paris 06, Inserm, CNRS, Institut du cerveau et de la moelle (ICM), Institut de la Mémoire et de la Maladie d'Alzheimer (IM2A), Hôpital Pitié-Salpêtrière, Boulevard de l'hôpital , Paris , France.
authors.forename: K
authors.initials: K
authors.lastname: Rojkova
authors.affiliation: g Medical Research Council Centre for Neuropsychiatric Genetics and Genomics , Cardiff University , Cardiff , UK.
authors.forename: V
authors.initials: V
authors.lastname: Escott-Price
authors.affiliation: h Département de Neurologie , Sorbonne Université, Université Pierre et Marie Curie, Paris 06 UMR S 1127, Institut National de Santé et en Recherche Médicale (INSERM) U 1127 and CIC-1422, Centre National de Recherche Scientifique U 7225, Institut du Cerveau et de la Moelle Epinière, Assistance Publique Hôpitaux de Paris, Hôpital Pitié-Salpêtrière , Paris , France.
authors.forename: J-C
authors.initials: JC
authors.lastname: Corvol
authors.affiliation: i President, Federal Institute for Drugs and Medical Devices (BfArM) , Bonn , Germany.
authors.forename: K
authors.initials: K
authors.lastname: Broich
authors.affiliation: b Département de Neurologie , Sorbonne Universités, Université Pierre et Marie Curie (UPMC), Paris 06, Inserm, CNRS, Institut du cerveau et de la moelle (ICM), Institut de la Mémoire et de la Maladie d'Alzheimer (IM2A), Hôpital Pitié-Salpêtrière, Boulevard de l'hôpital , Paris , France.
authors.forename: B
authors.initials: B
authors.lastname: Dubois
authors.affiliation: a AXA Research Fund & UPMC Chair , Paris , France.|b Département de Neurologie , Sorbonne Universités, Université Pierre et Marie Curie (UPMC), Paris 06, Inserm, CNRS, Institut du cerveau et de la moelle (ICM), Institut de la Mémoire et de la Maladie d'Alzheimer (IM2A), Hôpital Pitié-Salpêtrière, Boulevard de l'hôpital , Paris , France.
authors.forename: S
authors.initials: S
authors.lastname: Lista
mesh_terms: D000544:Alzheimer Disease; D015415:Biomarkers; D006301:Health Services Needs and Demand; D006801:Humans; D007391:International Cooperation; D057285:Precision Medicine / Q000639:trends*
chemical_list: D015415:Biomarkers
keywords: Alzheimer precision medicine initiative; Alzheimer’s disease; biomarkers; integrative disease modeling; precision medicine; precision medicine initiative; systems biology; systems medicine