Preclinical to phase II amyloid beta (Aβ) peptide modulators under investigation for Alzheimer’s disease

Beta-Site Amyloid Precursor Protein Cleaving Enzyme 1 Inhibition Impairs Synaptic Plasticity via Seizure Protein 6

(2018) Kaichuan Zhu et al.   BIOLOGICAL PSYCHIATRY

The Quest for Small Molecules as Amyloid Inhibiting Therapies for Alzheimer's Disease

(2017) Hozefa Amijee et al.   JOURNAL OF ALZHEIMERS DISEASE

A Multi-Center Randomized Proof-of-Concept Clinical Trial Applying [18F]FDG-PET for Evaluation of Metabolic Therapy with Rosiglitazone XR in Mild to Moderate Alzheimer's Disease

(2017) Sofia Tzimopoulou et al.   JOURNAL OF ALZHEIMERS DISEASE

Future Therapeutics in Alzheimer’s Disease: Development Status of BACE Inhibitors

(2016) Genevieve Evin   BIODRUGS

Amyloid-β peptide protects against microbial infection in mouse and worm models of Alzheimer’s disease

(2016) Deepak Kumar Vijaya Kumar et al.   Science Translational Medicine

Pharmacological BACE1 and BACE2 inhibition induces hair depigmentation by inhibiting PMEL17 processing in mice

(2016) Derya R. Shimshek et al.   Scientific Reports

Learning by Failing: Ideas and Concepts to Tackle γ-Secretases in Alzheimer's Disease and Beyond

(2015) Bart De Strooper et al.   Annual Review of Pharmacology and Toxicology

Pharmacological Inhibition of BACE1 Impairs Synaptic Plasticity and Cognitive Functions

(2015) Severin Filser et al.   BIOLOGICAL PSYCHIATRY

Protein amino-terminal modifications and proteomic approaches for N-terminal profiling

(2015) Zon W Lai et al.   CURRENT OPINION IN CHEMICAL BIOLOGY

The Potent BACE1 Inhibitor LY2886721 Elicits Robust Central A  Pharmacodynamic Responses in Mice, Dogs, and Humans

(2015) P. C. May et al.   JOURNAL OF NEUROSCIENCE

A novel BACE inhibitor NB-360 shows a superior pharmacological profile and robust reduction of amyloid-β and neuroinflammation in APP transgenic mice

(2015) Ulf Neumann et al.   Molecular Neurodegeneration

Intravenous immunoglobulin in neurology—mode of action and clinical efficacy

(2015) Jan D. Lünemann et al.   Nature Reviews Neurology

MRZ-99030 – A novel modulator of Aβ aggregation: I – Mechanism of action (MoA) underlying the potential neuroprotective treatment of Alzheimer's disease, glaucoma and age-related macular degeneration (AMD)

(2015) Christopher G. Parsons et al.   NEUROPHARMACOLOGY

MRZ-99030 – A novel modulator of Aβ aggregation: II – Reversal of Aβ oligomer-induced deficits in long-term potentiation (LTP) and cognitive performance in rats and mice

(2015) Gerhard Rammes et al.   NEUROPHARMACOLOGY

Mouse strain and brain region-specific expression of the glutaminyl cyclases QC and isoQC

(2014) Corinna Höfling et al.   INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE

Insulin sensitizers improve learning and attenuate tau hyperphosphorylation and neuroinflammation in 3xTg-AD mice

(2014) Yang Yu et al.   JOURNAL OF NEURAL TRANSMISSION

Targeting the β secretase BACE1 for Alzheimer's disease therapy

(2014) Riqiang Yan et al.   LANCET NEUROLOGY

Rosiglitazone prevents the memory deficits induced by amyloid-beta oligomers via inhibition of inflammatory responses

(2014) Shujun Xu et al.   NEUROSCIENCE LETTERS

Truncated and modified amyloid-beta species

(2014) Markus P Kummer et al.   Alzheimers Research & Therapy

β-secretase inhibitor; a promising novel therapeutic drug in Alzheimer’s disease

(2014) Kelly Willemijn Menting et al.   Frontiers in Aging Neuroscience

The novel BACE inhibitor MK-8931 dramatically lowers CSF beta-amyloid in patients with mild-to-moderate Alzheimer's disease

(2013) Mark Forman et al.   Alzheimers & Dementia

Pyroglutamate-3 Amyloid-β Deposition in the Brains of Humans, Non-Human Primates, Canines, and Alzheimer Disease–Like Transgenic Mouse Models

(2013) Jeffrey L. Frost et al.   AMERICAN JOURNAL OF PATHOLOGY

CHF5074 Reduces Biomarkers of Neuroinflammation in Patients with Mild Cognitive Impairment: A 12-Week, Double-Blind, Placebo- Controlled Study

(2013) Joel Ross et al.   Current Alzheimer Research

Allosteric inhibition of BACE1 by an exosite-binding antibody

(2013) Weiru Wang et al.   CURRENT OPINION IN STRUCTURAL BIOLOGY

First-in-human study of E2609, a novel BACE1 inhibitor, demonstrates prolonged reductions in plasma beta-amyloid levels after single dosing

(2012) Robert Lai et al.   Alzheimers & Dementia

EHT0202 in Alzheimers Disease: A 3-Month, Randomized, Placebo- Controlled, Double-Blind Study

(2012) B. Vellas et al.   Current Alzheimer Research

Posiphen as a candidate drug to lower CSF amyloid precursor protein, amyloid-β peptide and τ levels: target engagement, tolerability and pharmacokinetics in humans

(2012) Maria L Maccecchini et al.   JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY

Neurotoxicity and Memory Deficits Induced by Soluble Low-Molecular-Weight Amyloid- 1-42 Oligomers Are Revealed In Vivo by Using a Novel Animal Model

(2012) J. Brouillette et al.   JOURNAL OF NEUROSCIENCE

Neutralization of Soluble, Synaptotoxic Amyloid   Species by Antibodies Is Epitope Specific

(2012) W. Zago et al.   JOURNAL OF NEUROSCIENCE

Modulation of γ-secretase by EVP-0015962 reduces amyloid deposition and behavioral deficits in Tg2576 mice

(2012) Kathryn Rogers et al.   Molecular Neurodegeneration

The toxic Aβ oligomer and Alzheimer's disease: an emperor in need of clothes

(2012) Iryna Benilova et al.   NATURE NEUROSCIENCE

Preventing Alzheimer's Disease

(2012) D. J. Selkoe   SCIENCE

Synapses and Alzheimer's Disease

(2012) M. Sheng et al.   Cold Spring Harbor Perspectives in Biology

Postsynaptic Receptors for Amyloid-β Oligomers as Mediators of Neuronal Damage in Alzheimer’s Disease

(2012) Margarita C. Dinamarca et al.   Frontiers in Physiology

Aβ Oligomer-Induced Synapse Degeneration in Alzheimer’s Disease

(2011) Kyle C. Wilcox et al.   CELLULAR AND MOLECULAR NEUROBIOLOGY

Rosiglitazone Does Not Improve Cognition or Global Function when Used as Adjunctive Therapy to AChE Inhibitors in Mild-to-Moderate Alzheimers Disease: Two Phase 3 Studies

(2011) C. Harrington et al.   Current Alzheimer Research

Current and Emerging Drug Treatment Options for Alzheimerʼs Disease

(2011) Nathan Herrmann et al.   DRUGS

Pyroglutamate Amyloid-β (Aβ): A Hatchet Man in Alzheimer Disease

(2011) Sadim Jawhar et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Soluble Aβ oligomer production and toxicity

(2011) Megan E. Larson et al.   JOURNAL OF NEUROCHEMISTRY

Rosiglitazone Improves Spatial Memory and Decreases Insoluble Aβ1–42 in APP/PS1 Mice

(2011) Julie-Ann O’Reilly et al.   Journal of Neuroimmune Pharmacology

Alzheimer's disease: synapses gone cold

(2011) Robert M Koffie et al.   Molecular Neurodegeneration

Small-molecule conversion of toxic oligomers to nontoxic β-sheet–rich amyloid fibrils

(2011) Jan Bieschke et al.   Nature Chemical Biology

Resolving controversies on the path to Alzheimer's therapeutics

(2011) Dennis J Selkoe   NATURE MEDICINE

Preferential accumulation of amyloid-beta in presynaptic glutamatergic terminals (VGluT1 and VGluT2) in Alzheimer's disease cortex

(2011) Sophie Sokolow et al.   NEUROBIOLOGY OF DISEASE

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

(2011) S. Salloway et al.   NEUROLOGY

Nitration of Tyrosine 10 Critically Enhances Amyloid β Aggregation and Plaque Formation

(2011) Markus P. Kummer et al.   NEURON

Therapeutic significance of NR2B-containing NMDA receptors and mGluR5 metabotropic glutamate receptors in mediating the synaptotoxic effects of β-amyloid oligomers on long-term potentiation (LTP) in murine hippocampal slices

(2011) Gerhard Rammes et al.   NEUROPHARMACOLOGY

A Therapeutic Antibody Targeting BACE1 Inhibits Amyloid-  Production in Vivo

(2011) J. K. Atwal et al.   Science Translational Medicine

Boosting Brain Uptake of a Therapeutic Antibody by Reducing Its Affinity for a Transcytosis Target

(2011) Y. J. Yu et al.   Science Translational Medicine

Amyloid β oligomers induce Ca2+ dysregulation and neuronal death through activation of ionotropic glutamate receptors

(2010) Elena Alberdi et al.   CELL CALCIUM

Rosiglitazone Monotherapy in Mild-to-Moderate Alzheimer’s Disease: Results from a Randomized, Double-Blind, Placebo-Controlled Phase III Study

(2010) Michael Gold et al.   DEMENTIA AND GERIATRIC COGNITIVE DISORDERS

Molecular mechanisms of neurodegeneration in Alzheimer's disease

(2010) L. Crews et al.   HUMAN MOLECULAR GENETICS

Many Neuronal and Behavioral Impairments in Transgenic Mouse Models of Alzheimer's Disease Are Independent of Caspase Cleavage of the Amyloid Precursor Protein

(2010) J. A. Harris et al.   JOURNAL OF NEUROSCIENCE

Generation and Therapeutic Efficacy of Highly Oligomer-Specific  -Amyloid Antibodies

(2010) H. Hillen et al.   JOURNAL OF NEUROSCIENCE

Alzheimer's disease: strategies for disease modification

(2010) Martin Citron   NATURE REVIEWS DRUG DISCOVERY

ADDLs and the signaling web that leads to Alzheimer’s disease

(2010) Grant A. Krafft et al.   NEUROPHARMACOLOGY

Clinical trials of EHT 0202, a neuroprotective and procognitive alpha-secretase stimulator for Alzheimer's disease

(2009) Laurent Desire et al.   Alzheimers & Dementia

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

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

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

Picomolar Amyloid-  Positively Modulates Synaptic Plasticity and Memory in Hippocampus

(2009) D. Puzzo et al.   JOURNAL OF NEUROSCIENCE

 -Amyloid Monomers Are Neuroprotective

(2009) M. L. Giuffrida et al.   JOURNAL OF NEUROSCIENCE

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

Amyloid-β as a positive endogenous regulator of release probability at hippocampal synapses

(2009) Efrat Abramov et al.   NATURE NEUROSCIENCE

γ-Secretase in biology and medicine

(2009) Michael S. Wolfe   SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY

Cognitive-Performance Recovery of Alzheimer's Disease Model Mice by Modulation of Early Soluble Amyloidal Assemblies

(2008) Anat Frydman-Marom et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

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

Soluble oligomers of the amyloid β-protein impair synaptic plasticity and behavior

(2008) Dennis J. Selkoe   BEHAVIOURAL BRAIN RESEARCH

Rosiglitazone reverses memory decline and hippocampal glucocorticoid receptor down-regulation in an Alzheimer’s disease mouse model

(2008) Luis Escribano et al.   BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

Simultaneous Manipulation of Multiple Brain Targets by Green Tea Catechins: A Potential Neuroprotective Strategy for Alzheimer and Parkinson Diseases

(2008) Silvia A. Mandel et al.   CNS Neuroscience & Therapeutics

Structure-Function Implications in Alzheimers Disease: Effect of Aβ Oligomers at Central Synapses

(2008) Waldo Cerpa et al.   Current Alzheimer Research

Recent Progress in the Medicinal Chemistry of γ-Secretase Inhibitors

(2008) Richard Olson et al.   CURRENT TOPICS IN MEDICINAL CHEMISTRY

Therapeutic Potential of γ -Secretase Inhibitors and Modulators

(2008) Bruno Imbimbo   CURRENT TOPICS IN MEDICINAL CHEMISTRY

Structural Classification of Toxic Amyloid Oligomers

(2008) Charles G. Glabe   JOURNAL OF BIOLOGICAL CHEMISTRY

Anti-oligomeric Aβ Single-chain Variable Domain Antibody Blocks Aβ-induced Toxicity Against Human Neuroblastoma Cells

(2008) Andleeb Zameer et al.   JOURNAL OF MOLECULAR BIOLOGY

Glutaminyl cyclase inhibition attenuates pyroglutamate Aβ and Alzheimer's disease–like pathology

(2008) Stephan Schilling et al.   NATURE MEDICINE

Amyloid-β protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory

(2008) Ganesh M Shankar et al.   NATURE MEDICINE

Anti-ADDL antibodies differentially block oligomer binding to hippocampal neurons

(2008) P.J. Shughrue et al.   NEUROBIOLOGY OF AGING

Rapid Restoration of Cognition in Alzheimer's Transgenic Mice with 8-Hydroxy Quinoline Analogs Is Associated with Decreased Interstitial Aβ

(2008) Paul A. Adlard et al.   NEURON

Alzheimer's disease-type neuronal tau hyperphosphorylation induced by Aβ oligomers

(2007) Fernanda G. De Felice et al.   NEUROBIOLOGY OF AGING