title: Alzheimer disease research in the 21st century: past and current failures, new perspectives and funding priorities.
abstract: Much of Alzheimer disease (AD) research has been traditionally based on the use of animals, which have been extensively applied in an effort to both improve our understanding of the pathophysiological mechanisms of the disease and to test novel therapeutic approaches. However, decades of such research have not effectively translated into substantial therapeutic success for human patients. Here we critically discuss these issues in order to determine how existing human-based methods can be applied to study AD pathology and develop novel therapeutics. These methods, which include patient-derived cells, computational analysis and models, together with large-scale epidemiological studies represent novel and exciting tools to enhance and forward AD research. In particular, these methods are helping advance AD research by contributing multifactorial and multidimensional perspectives, especially considering the crucial role played by lifestyle risk factors in the determination of AD risk. In addition to research techniques, we also consider related pitfalls and flaws in the current research funding system. Conversely, we identify encouraging new trends in research and government policy. In light of these new research directions, we provide recommendations regarding prioritization of research funding. The goal of this document is to stimulate scientific and public discussion on the need to explore new avenues in AD research, considering outcome and ethics as core principles to reliably judge traditional research efforts and eventually undertake new research strategies.
authors.affiliation: Physicians Committee for Responsible Medicine, Washington, DC, USA.
authors.forename: Francesca
authors.initials: F
authors.lastname: Pistollato
authors.affiliation: Green Neuroscience Laboratory, Neurolinx Research Institute, San Diego, CA, USA.
authors.forename: Elan L
authors.initials: EL
authors.lastname: Ohayon
authors.affiliation: Physicians Committee for Responsible Medicine, Washington, DC, USA.|Green Neuroscience Laboratory, Neurolinx Research Institute, San Diego, CA, USA.
authors.forename: Ann
authors.initials: A
authors.lastname: Lam
authors.affiliation: Research and Toxicology Department, Humane Society International, London, UK.
authors.forename: Gillian R
authors.initials: GR
authors.lastname: Langley
authors.affiliation: Cellular Dynamics International, Madison, WI, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Novak
authors.affiliation: CAAT, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
authors.forename: David
authors.initials: D
authors.lastname: Pamies
authors.affiliation: College of Sciences, University of Texas at San Antonio, San Antonio, TX, USA.
authors.forename: George
authors.initials: G
authors.lastname: Perry
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Eugenia
authors.initials: E
authors.lastname: Trushina
authors.affiliation: Centre for Biomedical Sciences, School of Biological Sciences, Royal Holloway University of London, Egham, UK.
authors.forename: Robin S B
authors.initials: RS
authors.lastname: Williams
authors.affiliation: Division of Clinical Education, Midwestern University, Glendale, AZ, USA.|Division of Neurobiology, Barrow Neurological Institute, Phoenix, AZ, USA.
authors.forename: Alex E
authors.initials: AE
authors.lastname: Roher
authors.affiliation: CAAT, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hartung
authors.affiliation: Department of Psychology, University of Quebec/Montreal, Montreal, Canada.
authors.forename: Stevan
authors.initials: S
authors.lastname: Harnad
authors.affiliation: Physicians Committee for Responsible Medicine, Washington, DC, USA.
authors.forename: Neal
authors.initials: N
authors.lastname: Barnard
authors.affiliation: Section of Nutrition and Nutritional Epidemiology, Department of Internal Medicine, Rush University, Chicago, IL, USA.
authors.forename: Martha Clare
authors.initials: MC
authors.lastname: Morris
authors.affiliation: Physicians Committee for Responsible Medicine, Washington, DC, USA.
authors.forename: Mei-Chun
authors.initials: MC
authors.lastname: Lai
authors.affiliation: Physicians Committee for Responsible Medicine, Washington, DC, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Merkley
authors.affiliation: Physicians Committee for Responsible Medicine, Washington, DC, USA.
authors.forename: P Charukeshi
authors.initials: PC
authors.lastname: Chandrasekera
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism / Q000628:therapy*; D000818:Animals; D035843:Biomedical Research / Q000639:trends*; D003198:Computer Simulation; D004195:Disease Models, Animal; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology; D009316:National Institutes of Health (U.S.); D059906:Neuroimaging; D012107:Research Design; D012109:Research Support as Topic; D012307:Risk Factors; D014481:United States
keywords: Alzheimer disease; Gerotarget; animal models; computational models; human methods; induced pluripotent stem cells