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

Antiamyloid Therapy for Alzheimer's Disease — Are We on the Right Road?

(2014) Eric Karran et al.   NEW ENGLAND JOURNAL OF MEDICINE

Two Phase 3 Trials of Bapineuzumab in Mild-to-Moderate Alzheimer's Disease

(2014) Stephen Salloway et al.   NEW ENGLAND JOURNAL OF MEDICINE

Phase 3 Trials of Solanezumab for Mild-to-Moderate Alzheimer's Disease

(2014) Rachelle S. Doody et al.   NEW ENGLAND JOURNAL OF MEDICINE

Inflammatory components in human Alzheimer’s disease and after active amyloid-β42 immunization

(2013) Elina Zotova et al.   BRAIN

Intravenous immunoglobulin for treatment of mild-to-moderate Alzheimer's disease: a phase 2, randomised, double-blind, placebo-controlled, dose-finding trial

(2013) Richard Dodel et al.   LANCET NEUROLOGY

Amyloid imaging and CSF biomarkers in predicting cognitive impairment up to 7.5 years later

(2013) C. M. Roe et al.   NEUROLOGY

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

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

Safety and biomarker effects of solanezumab in patients with Alzheimer’s disease

(2012) Martin Farlow et al.   Alzheimers & Dementia

Effect of Immunotherapy With Bapineuzumab on Cerebrospinal Fluid Biomarker Levels in Patients With Mild to Moderate Alzheimer Disease

(2012) Henrik Zetterberg   ARCHIVES OF NEUROLOGY

The mechanism of γ-Secretase dysfunction in familial Alzheimer disease

(2012) Lucía Chávez-Gutiérrez et al.   EMBO JOURNAL

Sustained levels of antibodies against Aβ in amyloid-rich regions of the CNS following intravenous dosing in human APP transgenic mice

(2012) Frédérique Bard et al.   EXPERIMENTAL NEUROLOGY

Solanezumab for the treatment of mild-to-moderate Alzheimer’s disease

(2012) Bruno P Imbimbo et al.   Expert Review of Clinical Immunology

First and Second Generation γ-Secretase Modulators (GSMs) Modulate Amyloid-β (Aβ) Peptide Production through Different Mechanisms

(2012) Tomas Borgegard et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Differential Effects between  -Secretase Inhibitors and Modulators on Cognitive Function in Amyloid Precursor Protein-Transgenic and Nontransgenic Mice

(2012) Y. Mitani et al.   JOURNAL OF NEUROSCIENCE

Transient pharmacologic lowering of Aβ production prior to deposition results in sustained reduction of amyloid plaque pathology

(2012) Pritam Das et al.   Molecular Neurodegeneration

A Plaque-Specific Antibody Clears Existing β-amyloid Plaques in Alzheimer's Disease Mice

(2012) Ronald B. DeMattos et al.   NEURON

Tramiprosate in mild-to-moderate Alzheimer’s disease – a randomized, double-blind, placebo-controlled, multi-centre study (the Alphase Study)

(2011) Paul S. Aisen et al.   Archives of Medical Science

NSAID-Based γ-Secretase Modulators Do Not Bind to the Amyloid-β Polypeptide

(2011) Paul J. Barrett et al.   BIOCHEMISTRY

γ-Secretase inhibitors and modulators for Alzheimer’s disease

(2011) Michael S. Wolfe   JOURNAL OF NEUROCHEMISTRY

γ-Secretase modulators do not induce Aβ-rebound and accumulation of β-C-terminal fragment

(2011) Ting Li et al.   JOURNAL OF NEUROCHEMISTRY

The amyloid cascade hypothesis for Alzheimer's disease: an appraisal for the development of therapeutics

(2011) Eric Karran et al.   NATURE REVIEWS DRUG DISCOVERY

A Single Ascending Dose Study of Bapineuzumab in Patients With Alzheimer Disease

(2010) Ronald S. Black et al.   ALZHEIMER DISEASE & ASSOCIATED DISORDERS

Design, synthesis, and in vivo characterization of a novel series of tetralin amino imidazoles as γ-secretase inhibitors: Discovery of PF-3084014

(2010) Michael A. Brodney et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Beneficial effect of human anti-amyloid-β active immunization on neurite morphology and tau pathology

(2010) Alberto Serrano-Pozo et al.   BRAIN

The presence of sodium dodecyl sulphate-stable Aβ dimers is strongly associated with Alzheimer-type dementia

(2010) Jessica M. Mc Donald et al.   BRAIN

Safety and Changes in Plasma and Cerebrospinal Fluid Amyloid β After a Single Administration of an Amyloid β Monoclonal Antibody in Subjects With Alzheimer Disease

(2010) Eric R. Siemers et al.   CLINICAL NEUROPHARMACOLOGY

Human intravenous immunoglobulin provides protection against Aβ toxicity by multiple mechanisms in a mouse model of Alzheimer's disease

(2010) Johanna Magga et al.   Journal of Neuroinflammation

Investigation of the noncovalent interactions between anti-amyloid agents and amyloid β peptides by ESI-MS

(2010) Eric Martineau et al.   JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY

11C-PiB PET assessment of change in fibrillar amyloid-β load in patients with Alzheimer's disease treated with bapineuzumab: a phase 2, double-blind, placebo-controlled, ascending-dose study

(2010) Juha O Rinne et al.   LANCET NEUROLOGY

Alzheimer's disease: clinical trials and drug development

(2010) Francesca Mangialasche et al.   LANCET NEUROLOGY

The biochemical aftermath of anti-amyloid immunotherapy

(2010) Chera L Maarouf et al.   Molecular Neurodegeneration

Nonsteroidal anti-inflammatory drugs are associated with increased neuritic plaques

(2010) J. A. Sonnen et al.   NEUROLOGY

Microglial alterations in human Alzheimer's disease following Aβ42 immunization

(2010) E. Zotova et al.   NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY

Proteases and Proteolysis in Alzheimer Disease: A Multifactorial View on the Disease Process

(2010) Bart De Strooper   PHYSIOLOGICAL REVIEWS

Discovery and Evaluation of BMS-708163, a Potent, Selective and Orally Bioavailable γ-Secretase Inhibitor

(2010) Kevin W. Gillman et al.   ACS Medicinal Chemistry Letters

A γ-secretase inhibitor decreases amyloid-β production in the central nervous system

(2009) Randall J. Bateman et al.   ANNALS OF NEUROLOGY

Cerebrospinal fluid biomarker signature in Alzheimer's disease neuroimaging initiative subjects

(2009) Leslie M. Shaw et al.   ANNALS OF NEUROLOGY

Nonspecificity of Binding of γ-Secretase Modulators to the Amyloid Precursor Protein

(2009) Andrew J. Beel et al.   BIOCHEMISTRY

Development of semagacestat (LY450139), a functional γ-secretase inhibitor, for the treatment of Alzheimer's disease

(2009) David B Henley et al.   EXPERT OPINION ON PHARMACOTHERAPY

Effect of Tarenflurbil on Cognitive Decline and Activities of Daily Living in Patients With Mild Alzheimer DiseaseA Randomized Controlled Trial

(2009) Robert C. Green   JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION

Characterizing the Appearance and Growth of Amyloid Plaques in APP/PS1 Mice

(2009) P. Yan et al.   JOURNAL OF NEUROSCIENCE

Begacestat (GSI-953): A Novel, Selective Thiophene Sulfonamide Inhibitor of Amyloid Precursor Protein  -Secretase for the Treatment of Alzheimer's Disease

(2009) R. L. Martone et al.   JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS

Existing plaques and neuritic abnormalities in APP:PS1 mice are not affected by administration of the gamma-secretase inhibitor LY-411575

(2009) Monica Garcia-Alloza et al.   Molecular Neurodegeneration

Risk of dementia and AD with prior exposure to NSAIDs in an elderly community-based cohort

(2009) J.C.S. Breitner et al.   NEUROLOGY

IV immunoglobulin is associated with a reduced risk of Alzheimer disease and related disorders

(2009) H. Fillit et al.   NEUROLOGY

A phase 2 multiple ascending dose trial of bapineuzumab in mild to moderate Alzheimer disease

(2009) S. Salloway et al.   NEUROLOGY

Age, Neuropathology, and Dementia

(2009) George M. Savva et al.   NEW ENGLAND JOURNAL OF MEDICINE

Phase 2 Safety Trial Targeting Amyloid β Production With a γ-Secretase Inhibitor in Alzheimer Disease

(2008) Adam S. Fleisher et al.   ARCHIVES OF NEUROLOGY

The Amyloid-β Rise and γ-Secretase Inhibitor Potency Depend on the Level of Substrate Expression

(2008) Catherine R. Burton et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Immunotherapy Reduces Vascular Amyloid-  in PDAPP Mice

(2008) S. Schroeter et al.   JOURNAL OF NEUROSCIENCE

Dynamics of A  Turnover and Deposition in Different  -Amyloid Precursor Protein Transgenic Mouse Models Following  -Secretase Inhibition

(2008) D. Abramowski et al.   JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS

Long-term effects of Aβ42 immunisation in Alzheimer's disease: follow-up of a randomised, placebo-controlled phase I trial

(2008) Clive Holmes et al.   LANCET

Efficacy and safety of tarenflurbil in mild to moderate Alzheimer's disease: a randomised phase II trial

(2008) Gordon K Wilcock et al.   LANCET NEUROLOGY

Substrate-targeting γ-secretase modulators

(2008) Thomas L. Kukar et al.   NATURE

18-Month study of intravenous immunoglobulin for treatment of mild Alzheimer disease

(2008) Norman R. Relkin et al.   NEUROBIOLOGY OF AGING

Antibody Capture of Soluble Aβ Does Not Reduce Cortical Aβ Amyloidosis in the PDAPP Mouse

(2008) Peter Seubert et al.   Neurodegenerative Diseases

Progress in the Active Immunotherapeutic Approach to Alzheimer’s Disease: Clinical Investigations into AN1792-Associated Meningoencephalitis

(2008) Michael Pride et al.   Neurodegenerative Diseases

Relation of NSAIDs to incident AD, change in cognitive function, and AD pathology

(2008) Z. Arvanitakis et al.   NEUROLOGY

Peripheral and central biodistribution of 111In-labeled anti-beta-amyloid autoantibodies in a transgenic mouse model of Alzheimer's disease

(2008) Michael Bacher et al.   NEUROSCIENCE LETTERS