Drug Development for Alzheimer’s Disease: Microglia Induced Neuroinflammation as a Target?

Evaluating Potential QT Effects of JNJ-54861911, a BACE Inhibitor in Single- and Multiple-Ascending Dose Studies, and a Thorough QT Trial With Additional Retrospective Confirmation, Using Concentration-QTc Analysis

(2018) Maarten Timmers et al.   JOURNAL OF CLINICAL PHARMACOLOGY

Alzheimer's disease research: the future of BACE inhibitors

(2018) Talha Burki   LANCET

ABBY

(2018) Jeffrey L. Cummings et al.   NEUROLOGY

A Next Generation Synthesis of BACE1 Inhibitor Verubecestat (MK-8931)

(2018) David A. Thaisrivongs et al.   ORGANIC LETTERS

Structural and kinetic basis for the selectivity of aducanumab for aggregated forms of amyloid-β

(2018) Joseph W. Arndt et al.   Scientific Reports

Discovery and Identification of an Endogenous Metabolite of Tramiprosate and Its Prodrug ALZ-801 that Inhibits Beta Amyloid Oligomer Formation in the Human Brain

(2018) John A. Hey et al.   CNS DRUGS

The BACE‐1 inhibitor CNP520 for prevention trials in Alzheimer's disease

(2018) Ulf Neumann et al.   EMBO Molecular Medicine

Pharmacokinetics of tazarotene and acitretin in psoriasis

(2018) Michael S. Heath et al.   Expert Opinion on Drug Metabolism & Toxicology

Gantenerumab: A Novel Human Anti-Aβ Antibody Demonstrates Sustained Cerebral Amyloid-β Binding and Elicits Cell-Mediated Removal of Human Amyloid-β

(2018) Bernd Bohrmann et al.   JOURNAL OF ALZHEIMERS DISEASE

Caspase-1 inhibition alleviates cognitive impairment and neuropathology in an Alzheimer’s disease mouse model

(2018) Joseph Flores et al.   Nature Communications

Pharmacodynamics of atabecestat (JNJ-54861911), an oral BACE1 inhibitor in patients with early Alzheimer’s disease: randomized, double-blind, placebo-controlled study

(2018) Maarten Timmers et al.   Alzheimers Research & Therapy

Amyloid positron emission tomography and cerebrospinal fluid results from a crenezumab anti-amyloid-beta antibody double-blind, placebo-controlled, randomized phase II study in mild-to-moderate Alzheimer’s disease (BLAZE)

(2018) Stephen Salloway et al.   Alzheimers Research & Therapy

BACE1 Inhibitor MK-8931 Alters Formation but Not Stability of Dendritic Spines

(2018) Tanja Blume et al.   Frontiers in Aging Neuroscience

FUNDAMANT: an interventional 72-week phase 1 follow-up study of AADvac1, an active immunotherapy against tau protein pathology in Alzheimer’s disease

(2018) Petr Novak et al.   Alzheimers Research & Therapy

The Function of the Mitochondrial Calcium Uniporter in Neurodegenerative Disorders

(2017) Yajin Liao et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

Potential of Low Dose Leuco-Methylthioninium Bis(Hydromethanesulphonate) (LMTM) Monotherapy for Treatment of Mild Alzheimer’s Disease: Cohort Analysis as Modified Primary Outcome in a Phase III Clinical Trial

(2017) Gordon K. Wilcock et al.   JOURNAL OF ALZHEIMERS DISEASE

Acitretin Use in Dermatology

(2017) Lyn C. Guenther et al.   JOURNAL OF CUTANEOUS MEDICINE AND SURGERY

Aducanumab Therapy Ameliorates Calcium Overload in a Mouse Model of Alzheimer's Disease

(2017) Kanchana K. Gamage et al.   JOURNAL OF NEUROSCIENCE

Safety and immunogenicity of the tau vaccine AADvac1 in patients with Alzheimer's disease: a randomised, double-blind, placebo-controlled, phase 1 trial

(2017) Petr Novak et al.   LANCET NEUROLOGY

A phase III randomized trial of gantenerumab in prodromal Alzheimer’s disease

(2017) Susanne Ostrowitzki et al.   Alzheimers Research & Therapy

Apolipoprotein E Genotype and Sex Risk Factors for Alzheimer Disease

(2017) Scott C. Neu et al.   JAMA Neurology

Amyloid-β Induces Caspase-Dependent Loss of PSD-95 and Synaptophysin Through NMDA Receptors

(2017) Jinping Liu et al.   JOURNAL OF ALZHEIMERS DISEASE

2016 Alzheimer's disease facts and figures

(2016)   Alzheimers & Dementia

Potential Role of (-)-Epigallocatechin-3-Gallate (EGCG) in the Secondary Prevention of Alzheimer Disease

(2016) Laura Xicota et al.   CURRENT DRUG TARGETS

Intranasal delivery of nanoparticle encapsulated tarenflurbil: A potential brain targeting strategy for Alzheimer's disease

(2016) Eameema Muntimadugu et al.   EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES

Pioglitazone for the treatment of Alzheimer’s disease

(2016) Daniela Galimberti et al.   EXPERT OPINION ON INVESTIGATIONAL DRUGS

AZD3293: Pharmacokinetic and Pharmacodynamic Effects in Healthy Subjects and Patients with Alzheimer’s Disease

(2016) Gvido Cebers et al.   JOURNAL OF ALZHEIMERS DISEASE

AZD3293: A Novel, Orally Active BACE1 Inhibitor with High Potency and Permeability and Markedly Slow Off-Rate Kinetics

(2016) Susanna Eketjäll et al.   JOURNAL OF ALZHEIMERS DISEASE

Two Phase 2 Multiple Ascending–Dose Studies of Vanutide Cridificar (ACC-001) and QS-21 Adjuvant in Mild-to-Moderate Alzheimer’s Disease

(2016) Florence Pasquier et al.   JOURNAL OF ALZHEIMERS DISEASE

Acitretin

(2016) Marcus G. Tan et al.   JOURNAL OF CUTANEOUS MEDICINE AND SURGERY

Discovery of the 3-Imino-1,2,4-thiadiazinane 1,1-Dioxide Derivative Verubecestat (MK-8931)–A β-Site Amyloid Precursor Protein Cleaving Enzyme 1 Inhibitor for the Treatment of Alzheimer’s Disease

(2016) Jack D. Scott et al.   JOURNAL OF MEDICINAL CHEMISTRY

Immunotherapy with Aducanumab Restores Calcium Homeostasis in Tg2576 Mice

(2016) Ksenia V. Kastanenka et al.   JOURNAL OF NEUROSCIENCE

Efficacy and safety of tau-aggregation inhibitor therapy in patients with mild or moderate Alzheimer's disease: a randomised, controlled, double-blind, parallel-arm, phase 3 trial

(2016) Serge Gauthier et al.   LANCET

The NLRP3 and NLRP1 inflammasomes are activated in Alzheimer’s disease

(2016) Marina Saresella et al.   Molecular Neurodegeneration

The antibody aducanumab reduces Aβ plaques in Alzheimer’s disease

(2016) Jeff Sevigny et al.   NATURE

A polarizing question: do M1 and M2 microglia exist?

(2016) Richard M Ransohoff   NATURE NEUROSCIENCE

Alzheimer’s diseaseCD33rs3865444 variant does not contribute to cognitive performance: Table 1.

(2016) Guiyou Liu et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

The BACE1 inhibitor verubecestat (MK-8931) reduces CNS  -amyloid in animal models and in Alzheimers disease patients

(2016) M. E. Kennedy et al.   Science Translational Medicine

Fenamate NSAIDs inhibit the NLRP3 inflammasome and protect against Alzheimer’s disease in rodent models

(2016) Michael J. D. Daniels et al.   Nature Communications

Amplified RLR signaling activation through an interferon-stimulated gene-endoplasmic reticulum stress-mitochondrial calcium uniporter protein loop

(2016) Jinbo Cheng et al.   Scientific Reports

CALHM1 deficiency impairs cerebral neuron activity and memory flexibility in mice

(2016) Valérie Vingtdeux et al.   Scientific Reports

Antibody-Mediated Targeting of Tau In Vivo Does Not Require Effector Function and Microglial Engagement

(2016) Seung-Hye Lee et al.   Cell Reports

Intracellular Calcium Dysregulation: Implications for Alzheimer’s Disease

(2016) Simona Magi et al.   Biomed Research International

Current Research Therapeutic Strategies for Alzheimer’s Disease Treatment

(2016) Jaume Folch et al.   NEURAL PLASTICITY

Structure of Crenezumab Complex with Aβ Shows Loss of β-Hairpin

(2016) Mark Ultsch et al.   Scientific Reports

Characterization of Dementia and Alzheimer’s Disease in an Older Population: Updated Incidence and Life Expectancy With and Without Dementia

(2015) Sarah E. Tom et al.   AMERICAN JOURNAL OF PUBLIC HEALTH

Interactions of innate and adaptive immunity in brain development and function

(2015) Anthony J. Filiano et al.   BRAIN RESEARCH

Microglial M1/M2 polarization and metabolic states

(2015) Ruben Orihuela et al.   BRITISH JOURNAL OF PHARMACOLOGY

Non-Steroidal Anti-Inflammatory Drugs as a Treatment for Alzheimer’s Disease: A Systematic Review and Meta-Analysis of Treatment Effect

(2015) Marina Miguel-Álvarez et al.   DRUGS & AGING

Neuroinflammation in Alzheimer's disease

(2015) Michael T Heneka et al.   LANCET NEUROLOGY

TREM2 variants and risk of Alzheimer’s disease: a meta-analysis

(2015) Yanjun Lu et al.   NEUROLOGICAL SCIENCES

A randomized, double-blind, placebo-controlled trial of resveratrol for Alzheimer disease

(2015) R. Scott Turner et al.   NEUROLOGY

Etanercept in Alzheimer disease: A randomized, placebo-controlled, double-blind, phase 2 trial

(2015) J. Butchart et al.   NEUROLOGY

Amyloid cascade hypothesis: Pathogenesis and therapeutic strategies in Alzheimer's disease

(2015) Sagar H. Barage et al.   NEUROPEPTIDES

Potential neuroprotective properties of epigallocatechin-3-gallate (EGCG)

(2015) Neha Atulkumar Singh et al.   Nutrition Journal

Mitochondrial calcium uniporter protein MCU is involved in oxidative stress-induced cell death

(2015) Yajin Liao et al.   Protein & Cell

First Administration of the Fc-Attenuated Anti-β Amyloid Antibody GSK933776 to Patients with Mild Alzheimer’s Disease: A Randomized, Placebo-Controlled Study

(2015) Niels Andreasen et al.   PLoS One

Adverse Effects of Cholinesterase Inhibitors in Dementia, According to the Pharmacovigilance Databases of the United-States and Canada

(2015) Thibault B. Ali et al.   PLoS One

Effect of TTP488 in patients with mild to moderate Alzheimer’s disease

(2014) Aaron H Burstein et al.   BMC Neurology

The Multifactorial Nature of Alzheimer's Disease for Developing Potential Therapeutics

(2014) M. Carreiras et al.   CURRENT TOPICS IN MEDICINAL CHEMISTRY

Coding variants in TREM2 increase risk for Alzheimer's disease

(2014) Sheng Chih Jin et al.   HUMAN MOLECULAR GENETICS

Transcriptome-Based Network Analysis Reveals a Spectrum Model of Human Macrophage Activation

(2014) Jia Xue et al.   IMMUNITY

Cytokine-Mediated Inhibition of Fibrillar Amyloid-  Peptide Degradation by Human Mononuclear Phagocytes

(2014) M. Yamamoto et al.   JOURNAL OF IMMUNOLOGY

Sex and gender differences in the causes of dementia: A narrative review

(2014) Walter A. Rocca et al.   MATURITAS

Increased CSF APPs-  levels in patients with Alzheimer disease treated with acitretin

(2014) K. Endres et al.   NEUROLOGY

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

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

Evidence of Trem2 Variant Associated with Triple Risk of Alzheimer’s Disease

(2014) Zainularifeen Abduljaleel et al.   PLoS One

Clioquinol promotes the degradation of metal-dependent amyloid-  (A ) oligomers to restore endocytosis and ameliorate A  toxicity

(2014) K. E. S. Matlack et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Modulation of β-amyloid by a single dose of GSK933776 in patients with mild Alzheimer’s disease: a phase I study

(2014) Thomas Leyhe et al.   Alzheimers Research & Therapy

First-in-man tau vaccine targeting structural determinants essential for pathological tau–tau interaction reduces tau oligomerisation and neurofibrillary degeneration in an Alzheimer’s disease model

(2014) Eva Kontsekova et al.   Alzheimers Research & Therapy

Clinical epidemiology of Alzheimer’s disease: assessing sex and gender differences

(2014) Michelle Mielke et al.   Clinical Epidemiology

Microglia Promote Learning-Dependent Synapse Formation through Brain-Derived Neurotrophic Factor

(2013) Christopher N. Parkhurst et al.   CELL

Integrated Systems Approach Identifies Genetic Nodes and Networks in Late-Onset Alzheimer’s Disease

(2013) Bin Zhang et al.   CELL

Canonical Nlrp3 Inflammasome Links Systemic Low-Grade Inflammation to Functional Decline in Aging

(2013) Yun-Hee Youm et al.   Cell Metabolism

Safety and Pharmacology of a Single Intravenous Dose of Ponezumab in Subjects With Mild-to-Moderate Alzheimer Disease

(2013) Jaren W. Landen et al.   CLINICAL NEUROPHARMACOLOGY

Impact of Apolipoprotein E on Alzheimer’s Disease

(2013) Paul Hauser et al.   Current Alzheimer Research

Bapineuzumab and solanezumab for Alzheimer's disease: is the ‘amyloid cascade hypothesis' still alive?

(2013) Haythum O Tayeb et al.   EXPERT OPINION ON BIOLOGICAL THERAPY

Genome-Wide Association Studies, Alzheimer Disease, and Understudied Populations

(2013) Robert L. Nussbaum   JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION

CALHM1 controls the Ca2+-dependent MEK, ERK, RSK and MSK signaling cascade in neurons

(2013) U. Dreses-Werringloer et al.   JOURNAL OF CELL SCIENCE

NLRP3 polymorphisms are associated with late-onset Alzheimer's disease in Han Chinese

(2013) Meng-Shan Tan et al.   JOURNAL OF NEUROIMMUNOLOGY

The NLRP3 Inflammasome in Alzheimer’s Disease

(2013) Meng-Shan Tan et al.   MOLECULAR NEUROBIOLOGY

Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease

(2013) Jean-Charles Lambert et al.   NATURE GENETICS

NLRP3 inflammasome activation: CD36 serves double duty

(2013) Jonathan C Kagan et al.   NATURE IMMUNOLOGY

CD36 coordinates NLRP3 inflammasome activation by facilitating intracellular nucleation of soluble ligands into particulate ligands in sterile inflammation

(2013) Frederick J Sheedy et al.   NATURE IMMUNOLOGY

CD33 Alzheimer's disease locus: altered monocyte function and amyloid biology

(2013) Elizabeth M Bradshaw et al.   NATURE NEUROSCIENCE

Alzheimer disease in the United States (2010-2050) estimated using the 2010 census

(2013) L. E. Hebert et al.   NEUROLOGY

Alzheimer’s Disease Risk Gene CD33 Inhibits Microglial Uptake of Amyloid Beta

(2013) Ana Griciuc et al.   NEURON

Microglia Actively Regulate the Number of Functional Synapses

(2013) Kyungmin Ji et al.   PLoS One

Dysregulation of neural calcium signaling in Alzheimer disease, bipolar disorder and schizophrenia

(2013) Michael J. Berridge   Prion

Alzheimer disease

(2013) Justin M. Nussbaum et al.   Prion

Microglial aging in the healthy CNS: phenotypes, drivers, and rejuvenation

(2013) Wai T. Wong   Frontiers in Cellular Neuroscience

Profile of gantenerumab and its potential in the treatment of Alzheimer's disease

(2013) Robert Nisticò et al.   Drug Design Development and Therapy

Early-onset Alzheimer's Disease: Nonamnestic Subtypes and Type 2 AD

(2012) Mario F. Mendez   ARCHIVES OF MEDICAL RESEARCH

Safety and Tolerability of the γ-Secretase Inhibitor Avagacestat in a Phase 2 Study of Mild to Moderate Alzheimer Disease

(2012) Vladimir Coric et al.   ARCHIVES OF NEUROLOGY

Effects of Single Doses of Avagacestat (BMS-708163) on Cerebrospinal Fluid Aβ Levels in Healthy Young Men

(2012) Gary Tong et al.   CLINICAL DRUG INVESTIGATION

A Placebo-Controlled, Multiple Ascending Dose Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of Avagacestat (BMS-708163) in Healthy Young and Elderly Subjects

(2012) Randy Dockens et al.   CLINICAL PHARMACOKINETICS

Gantenerumab for the treatment of Alzheimer's disease

(2012) Julien Delrieu et al.   EXPERT OPINION ON BIOLOGICAL THERAPY

Cognitive reserve in ageing and Alzheimer's disease

(2012) Yaakov Stern   LANCET NEUROLOGY

TPI-287, a New Taxane Family Member, Reduces the Brain Metastatic Colonization of Breast Cancer Cells

(2012) D. P. Fitzgerald et al.   MOLECULAR CANCER THERAPEUTICS

Aβ Toxicity in Alzheimer's Disease

(2012) Virve Cavallucci et al.   MOLECULAR NEUROBIOLOGY

NLRP3 is activated in Alzheimer’s disease and contributes to pathology in APP/PS1 mice

(2012) Michael T. Heneka et al.   NATURE

Etazolate, an α-secretase activator, reduces neuroinflammation and offers persistent neuroprotection following traumatic brain injury in mice

(2012) Eleni Siopi et al.   NEUROPHARMACOLOGY

Variant of TREM2 Associated with the Risk of Alzheimer's Disease

(2012) Thorlakur Jonsson et al.   NEW ENGLAND JOURNAL OF MEDICINE

TREM2 Variants in Alzheimer's Disease

(2012) Rita Guerreiro et al.   NEW ENGLAND JOURNAL OF MEDICINE

Advances in the pathogenesis of Alzheimer's disease: a re-evaluation of amyloid cascade hypothesis

(2012) Dong Suzhen et al.   Translational Neurodegeneration

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

Lack of Evidence for the Efficacy of Memantine in Mild Alzheimer Disease

(2011) Lon S. Schneider   ARCHIVES OF NEUROLOGY

Mechanism of Amyloid Removal in Patients With Alzheimer Disease Treated With Gantenerumab

(2011) Susanne Ostrowitzki   ARCHIVES OF NEUROLOGY

Tacrine Treatment at High Dose Suppresses the Recognition Memory in Juvenile and Adult Mice with Attention to Hepatotoxicity

(2011) Si-Yuan Pan et al.   BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY

The amyloid cascade hypothesis has misled the pharmaceutical industry

(2011)   BIOCHEMICAL SOCIETY TRANSACTIONS

Structural Basis of C-terminal β-Amyloid Peptide Binding by the Antibody Ponezumab for the Treatment of Alzheimer's Disease

(2011) Sherry L. La Porte et al.   JOURNAL OF MOLECULAR BIOLOGY

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 phase 2 randomized trial of ELND005, scyllo-inositol, in mild to moderate Alzheimer disease

(2011) S. Salloway et al.   NEUROLOGY

A randomized, double-blind, placebo-controlled trial of simvastatin to treat Alzheimer disease

(2011) M. Sano et al.   NEUROLOGY

Physiology of Microglia

(2011) Helmut Kettenmann et al.   PHYSIOLOGICAL REVIEWS

The Discovery of VX-745: A Novel and Selective p38α Kinase Inhibitor

(2011) John P. Duffy et al.   ACS Medicinal Chemistry Letters

A Randomized Pilot Clinical Trial of the Safety of Pioglitazone in Treatment of Patients With Alzheimer Disease

(2010) David S. Geldmacher et al.   ARCHIVES OF NEUROLOGY

Beyond the Cholinergic Hypothesis: Do Current Drugs Work in Alzheimer's Disease?

(2010) Alessandro Martorana et al.   CNS Neuroscience & Therapeutics

The secretases: enzymes with therapeutic potential in Alzheimer disease

(2010) Bart De Strooper et al.   Nature Reviews Neurology

Decreased Clearance of CNS  -Amyloid in Alzheimer's Disease

(2010) K. G. Mawuenyega et al.   SCIENCE

Synaptic degeneration in Alzheimer’s disease

(2009) Thomas Arendt   ACTA NEUROPATHOLOGICA

Protective actions of sex steroid hormones in Alzheimer’s disease

(2009) Christian J. Pike et al.   FRONTIERS IN NEUROENDOCRINOLOGY

Characterization of the microglial phenotype under specific pro-inflammatory and anti-inflammatory conditions: Effects of oligomeric and fibrillar amyloid-β

(2009) Alessandro Michelucci et al.   JOURNAL OF NEUROIMMUNOLOGY

Effect of tramiprosate in patients with mild-to-moderate alzheimer’s disease: Exploratory analyses of the MRI sub-group of the alphase study

(2009) S. Gauthier et al.   Journal of Nutrition Health & Aging

APP binds DR6 to trigger axon pruning and neuron death via distinct caspases

(2009) Anatoly Nikolaev et al.   NATURE

CD36 ligands promote sterile inflammation through assembly of a Toll-like receptor 4 and 6 heterodimer

(2009) Cameron R Stewart et al.   NATURE IMMUNOLOGY

Efficacy of PPAR-γ agonist pioglitazone in mild Alzheimer disease

(2009) Tomohiko Sato et al.   NEUROBIOLOGY OF AGING

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

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

Calcium signaling and neurodegenerative diseases

(2009) Ilya Bezprozvanny   TRENDS IN MOLECULAR MEDICINE

The amyloid cascade hypothesis

(2008) Amos D. Korczyn   Alzheimers & Dementia

Oxidative Stress Signaling in Alzheimers Disease

(2008) B. Su et al.   Current Alzheimer Research

Microglial dystrophy in the aged and Alzheimer's disease brain is associated with ferritin immunoreactivity

(2008) Kryslaine O. Lopes et al.   GLIA

Etazolate, a neuroprotective drug linking GABAAreceptor pharmacology to amyloid precursor protein processing

(2008) Maryline Marcade et al.   JOURNAL OF NEUROCHEMISTRY

Microglial Dysfunction and Defective  -Amyloid Clearance Pathways in Aging Alzheimer's Disease Mice

(2008) S. E. Hickman et al.   JOURNAL OF NEUROSCIENCE

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

Protective effects of NSAIDs on the development of Alzheimer disease

(2008) Steven C. Vlad et al.   NEUROLOGY

ApoE Promotes the Proteolytic Degradation of Aβ

(2008) Qingguang Jiang et al.   NEURON

Neuronal calcium mishandling and the pathogenesis of Alzheimer's disease

(2008) Ilya Bezprozvanny et al.   TRENDS IN NEUROSCIENCES

Menopausal transition: A possible risk factor for brain pathologic events

(2007) S.M. Bonomo et al.   NEUROBIOLOGY OF AGING