Clinical Trials for Disease-Modifying Therapies in Alzheimer’s Disease: A Primer, Lessons Learned, and a Blueprint for the Future

Alzheimer's Prevention Initiative: A Plan to Accelerate the Evaluation of Presymptomatic Treatments

(2018) Eric M. Reiman et al.   JOURNAL OF ALZHEIMERS DISEASE

Amyloid-β1-15/16 as a Marker for γ-Secretase Inhibition in Alzheimer's Disease

(2018) Erik Portelius et al.   JOURNAL OF ALZHEIMERS DISEASE

Association Between Elevated Brain Amyloid and Subsequent Cognitive Decline Among Cognitively Normal Persons

(2017) Michael C. Donohue et al.   JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION

The target product profile as a tool for regulatory communication: advantageous but underused

(2017) Adria Tyndall et al.   NATURE REVIEWS DRUG DISCOVERY

Alzheimer Disease Signature Neurodegeneration and APOE Genotype in Mild Cognitive Impairment With Suspected Non–Alzheimer Disease Pathophysiology

(2017) Stefanie Schreiber et al.   JAMA Neurology

Molecular inflation, attrition and the rule of five

(2016) Paul D. Leeson   ADVANCED DRUG DELIVERY REVIEWS

Amyloid PET Screening for Enrichment of Early-Stage Alzheimer Disease Clinical Trials

(2016) Jeff Sevigny et al.   ALZHEIMER DISEASE & ASSOCIATED DISORDERS

Longitudinal decline in mild-to-moderate Alzheimer's disease: Analyses of placebo data from clinical trials

(2016) Ronald G. Thomas et al.   Alzheimers & Dementia

Integration of 18FDG-PET Metabolic and Functional Connectomes in the Early Diagnosis and Prognosis of the Alzheimer's Disease

(2016) Antonio Giuliano Zippo et al.   Current Alzheimer Research

Brain neural synchronization and functional coupling in Alzheimer's disease as revealed by resting state EEG rhythms

(2016) Claudio Babiloni et al.   INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY

ADCOMS: a composite clinical outcome for prodromal Alzheimer's disease trials

(2016) Jinping Wang et al.   JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY

Alzheimer's disease

(2016) Philip Scheltens et al.   LANCET

The antibody aducanumab reduces Aβ plaques in Alzheimer’s disease

(2016) Jeff Sevigny et al.   NATURE

Phase II and phase III failures: 2013–2015

(2016) Richard K. Harrison   NATURE REVIEWS DRUG DISCOVERY

A/T/N: An unbiased descriptive classification scheme for Alzheimer disease biomarkers

(2016) Clifford R. Jack et al.   NEUROLOGY

Tau and Aβ imaging, CSF measures, and cognition in Alzheimer’s disease

(2016) Matthew R. Brier et al.   Science Translational Medicine

A single dose of the γ-secretase inhibitor semagacestat alters the cerebrospinal fluid peptidome in humans

(2016) Mikko Hölttä et al.   Alzheimers Research & Therapy

Evaluation of Tau Imaging in Staging Alzheimer Disease and Revealing Interactions Between β-Amyloid and Tauopathy

(2016) Liang Wang et al.   JAMA Neurology

Association of Cerebrospinal Fluid Neurofilament Light Concentration With Alzheimer Disease Progression

(2016) Henrik Zetterberg et al.   JAMA Neurology

Rodent models for Alzheimer’s disease drug discovery

(2015) Daniela Puzzo et al.   Expert Opinion on Drug Discovery

A framework to assess the value of subgroup analyses when the overall treatment effect is significant

(2015) Hong Sun et al.   Journal of Biopharmaceutical Statistics

18F-THK5351: A Novel PET Radiotracer for Imaging Neurofibrillary Pathology in Alzheimer Disease

(2015) R. Harada et al.   JOURNAL OF NUCLEAR MEDICINE

Multiple Effect of APOE Genotype on Clinical and Neuroimaging Biomarkers Across Alzheimer’s Disease Spectrum

(2015) Ying Liu et al.   MOLECULAR NEUROBIOLOGY

Alzheimer’s disease progression by geographical region in a clinical trial setting

(2015) David B Henley et al.   Alzheimers Research & Therapy

Comparing recruitment, retention, and safety reporting among geographic regions in multinational Alzheimer’s disease clinical trials

(2015) Joshua D Grill et al.   Alzheimers Research & Therapy

Alzheimer's disease

(2015) Colin L. Masters et al.   Nature Reviews Disease Primers

The Impact of Preclinical Irreproducibility on Drug Development

(2015) LP Freedman et al.   CLINICAL PHARMACOLOGY & THERAPEUTICS

A Novel Approach to Delayed-Start Analyses for Demonstrating Disease-Modifying Effects in Alzheimer’s Disease

(2015) Hong Liu-Seifert et al.   PLoS One

An empirically derived composite cognitive test score with improved power to track and evaluate treatments for preclinical Alzheimer's disease

(2014) Jessica B. Langbaum et al.   Alzheimers & Dementia

A critique of the drug discovery and phase 3 clinical programs targeting the amyloid hypothesis for Alzheimer disease

(2014) Eric Karran et al.   ANNALS OF NEUROLOGY

Economic analysis of opportunities to accelerate Alzheimer's disease research and development

(2014) Troy J. Scott et al.   Annals of the New York Academy of Sciences

Adaptive Clinical Trial Design

(2014) Shein-Chung Chow   Annual Review of Medicine

Advances in quantitative structure–activity relationship models of anti-Alzheimer’s agents

(2014) Pravin Ambure et al.   Expert Opinion on Drug Discovery

How to Use a Subgroup Analysis

(2014) Xin Sun et al.   JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION

CNS Amyloid- , Soluble APP-  and -  Kinetics during BACE Inhibition

(2014) J. A. Dobrowolska et al.   JOURNAL OF NEUROSCIENCE

Advancing research diagnostic criteria for Alzheimer's disease: the IWG-2 criteria

(2014) Bruno Dubois et al.   LANCET NEUROLOGY

A three-dimensional human neural cell culture model of Alzheimer’s disease

(2014) Se Hoon Choi et al.   NATURE

Lessons learned from the fate of AstraZeneca's drug pipeline: a five-dimensional framework

(2014) David Cook et al.   NATURE REVIEWS DRUG DISCOVERY

Clinical trial of an inhibitor of RAGE-A  interactions in Alzheimer disease

(2014) D. Galasko et al.   NEUROLOGY

Alzheimer’s disease drug-development pipeline: few candidates, frequent failures

(2014) Jeffrey L Cummings et al.   Alzheimers Research & Therapy

Effect of Potent γ-Secretase Modulator in Human Neurons Derived From Multiple Presenilin 1–Induced Pluripotent Stem Cell Mutant Carriers

(2014) Qing Liu et al.   JAMA Neurology

The Preclinical Alzheimer Cognitive Composite

(2014) Michael C. Donohue et al.   JAMA Neurology

A Map of Alzheimer’s Disease–Signaling Pathways: A Hope for Drug Target Discovery

(2013) S Ogishima et al.   CLINICAL PHARMACOLOGY & THERAPEUTICS

Discovering New Treatments for Alzheimer's Disease by Repurposing Approved Medications

(2013) Brian Appleby et al.   CURRENT TOPICS IN MEDICINAL CHEMISTRY

A Review: Treatment of Alzheimer’s Disease Discovered in Repurposed Agents

(2013) Brian S. Appleby et al.   DEMENTIA AND GERIATRIC COGNITIVE DISORDERS

Experimental models for predicting drug absorption and metabolism

(2013) Saeed Alqahtani et al.   Expert Opinion on Drug Metabolism & Toxicology

Utility of CSF in translational neuroscience

(2013) Elizabeth C. M. de Lange   JOURNAL OF PHARMACOKINETICS AND PHARMACODYNAMICS

Tracking pathophysiological processes in Alzheimer's disease: an updated hypothetical model of dynamic biomarkers

(2013) Clifford R Jack et al.   LANCET NEUROLOGY

Blood–brain-barriers in aging and in Alzheimer’s disease

(2013) Fernanda Marques et al.   Molecular Neurodegeneration

Alzheimer disease therapy—moving from amyloid-β to tau

(2013) Ezio Giacobini et al.   Nature Reviews Neurology

Innovation in Therapeutics Development at the NCATS

(2013) Christine M Colvis et al.   NEUROPSYCHOPHARMACOLOGY

A Phase 3 Trial of Semagacestat for Treatment of Alzheimer's Disease

(2013) Rachelle S. Doody et al.   NEW ENGLAND JOURNAL OF MEDICINE

Preclinical trials in autosomal dominant AD: Implementation of the DIAN-TU trial

(2013) S.M. Mills et al.   REVUE NEUROLOGIQUE

Animal Models of Alzheimer Disease

(2013) F. M. LaFerla et al.   Cold Spring Harbor Perspectives in Medicine

Epidemiology of Dementias and Alzheimer’s Disease

(2012) Ana Luisa Sosa-Ortiz et al.   ARCHIVES OF MEDICAL RESEARCH

Randomized, Double-Blind, Parallel-Group, 48-Week Study for Efficacy and Safety of a Higher-Dose Rivastigmine Patch (15 vs. 10 cm2) in Alzheimer’s Disease

(2012) Jeffrey Cummings et al.   DEMENTIA AND GERIATRIC COGNITIVE DISORDERS

Perspectives on molecular targeted therapies and clinical trials for neurodegenerative diseases

(2012) Masahisa Katsuno et al.   JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY

Amyloid-related imaging abnormalities in patients with Alzheimer's disease treated with bapineuzumab: a retrospective analysis

(2012) Reisa Sperling et al.   LANCET NEUROLOGY

Estimating sample sizes for predementia Alzheimer's trials based on the Alzheimer's Disease Neuroimaging Initiative

(2012) Joshua D. Grill et al.   NEUROBIOLOGY OF AGING

CSF VILIP-1 predicts rates of cognitive decline in early Alzheimer disease

(2012) R. Tarawneh et al.   NEUROLOGY

Drug delivery to the brain in Alzheimer's disease: Consideration of the blood–brain barrier

(2011) William A. Banks   ADVANCED DRUG DELIVERY REVIEWS

Amyloid-related imaging abnormalities in amyloid-modifying therapeutic trials: Recommendations from the Alzheimer’s Association Research Roundtable Workgroup

(2011) Reisa A. Sperling et al.   Alzheimers & Dementia

Safety and tolerability of donepezil 23 mg in moderate to severe Alzheimer's disease

(2011) Martin Farlow et al.   BMC Neurology

Structure-based druggability assessment—identifying suitable targets for small molecule therapeutics

(2011) Eric B Fauman et al.   CURRENT OPINION IN CHEMICAL BIOLOGY

Antibody-based therapy in Alzheimer's disease

(2011) Refik Pul et al.   EXPERT OPINION ON BIOLOGICAL THERAPY

Key Concepts of Clinical Trials: A Narrative Review

(2011) Craig A. Umscheid et al.   POSTGRADUATE MEDICINE

Accelerating drug discovery for Alzheimer's disease: best practices for preclinical animal studies

(2011) Diana W Shineman et al.   Alzheimers Research & Therapy

Globalization of Alzheimer's disease clinical trials

(2011) Jeffrey Cummings et al.   Alzheimers Research & Therapy

Principles of early drug discovery

(2010) JP Hughes et al.   BRITISH JOURNAL OF PHARMACOLOGY

Functional Alterations in Memory Networks in Early Alzheimer’s Disease

(2010) Reisa A. Sperling et al.   NEUROMOLECULAR MEDICINE

Cerebrospinal Fluid β-Amyloid 42 and Tau Proteins as Biomarkers of Alzheimer-Type Pathologic Changes in the Brain

(2009) Tero Tapiola et al.   ARCHIVES OF NEUROLOGY

Translational Medicine Lessons from Flurizan's Failure in Alzheimer's Disease (AD) Trial: Implication for Future Drug Discovery and Development for AD

(2009) Hong I. Wan et al.   CTS-Clinical and Translational Science

Exploratory drug safety: A discovery strategy to reduce attrition in development

(2009) Alan S. Bass et al.   JOURNAL OF PHARMACOLOGICAL AND TOXICOLOGICAL METHODS

Optimizing phase II of drug development for disease-modifying compounds

(2008) Jeffrey L. Cummings   Alzheimers & Dementia

High-content analysis in neuroscience

(2008) Mike Dragunow   NATURE REVIEWS NEUROSCIENCE

MRI correlates of neurofibrillary tangle pathology at autopsy: A voxel-based morphometry study

(2008) J. L. Whitwell et al.   NEUROLOGY