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Preclinical Models Of Alzheimer's Disease: Relevance And Translational Validity.

Kevin Mullane, Michael Williams
Published 2019 · Medicine
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The only drugs currently approved for the treatment of Alzheimer's Disease (AD) are four acetylcholinesterase inhibitors and the NMDA antagonist memantine. Apart from these drugs, which have minimal to no clinical benefit, the 40-year search for effective therapeutics to treat AD has resulted in a clinical failure rate of 100% not only for compounds that prevent brain amyloid deposition or remove existing amyloid plaques but also those acting by a variety of other putative disease-associated mechanisms. This indicates that the preclinical data generated from current AD targets to support the selection, optimization, and translation of new chemical entities (NCEs) and biologics to clinical trials is seriously compromised. While many of these failures reflect flawed hypotheses or a lack of adequate characterization of the preclinical pharmacodynamic and pharmacokinetic (PD/PK) properties of lead NCEs-including their bioavailability and toxicity-the conceptualization, validation, and interrogation of the current animal models of AD represent key limitations. The overwhelming majority of these AD models are transgenic, based on aspects of the amyloid hypothesis and the genetics of the familial form of the disease. As a result, these generally lack construct and predictive validity for the sporadic form of the human disease. The 170 or so transgenic models, perhaps the largest number ever focused on a single disease, use rodents, mainly mice, and in addition to amyloid also address aspects of tau causality with more complex multigene models including other presumed causative factors together with amyloid. This overview discusses the current animal models of AD in the context of both the controversies surrounding the causative role of amyloid in the disease and the need to develop validated models of cognitive function/dysfunction that more appropriately reflect the phenotype(s) of human aged-related dementias. © 2019 by John Wiley & Sons, Inc.
This paper references
10.1038/nprot.2006.116
Morris water maze: procedures for assessing spatial and related forms of learning and memory
Charles V Vorhees (2006)
10.1002/(SICI)1098-1063(1999)9:5<542::AID-HIPO8>3.0.CO;2-N
Exposing rats to a predator impairs spatial working memory in the radial arm water maze.
David M Diamond (1999)
10.1016/S0531-5565(96)00036-8
Senescence-accelerated mouse (SAM): A novel murine model of senescence
Toshio Takeda (1997)
10.1523/JNEUROSCI.6088-08.2009
Dissociating β-Amyloid from α7 Nicotinic Acetylcholine Receptor by a Novel Therapeutic Agent, S 24795, Normalizes α7 Nicotinic Acetylcholine and NMDA Receptor Function in Alzheimer's Disease Brain
Hoau-Yan Wang (2009)
10.1523/JNEUROSCI.3672-12.2013
A Transgenic Alzheimer Rat with Plaques, Tau Pathology, Behavioral Impairment, Oligomeric Aβ, and Frank Neuronal Loss
Robert M. Cohen (2013)
10.1126/science.1058189
Enhanced Neurofibrillary Degeneration in Transgenic Mice Expressing Mutant Tau and APP
Jada Lewis (2001)
10.1016/j.it.2016.12.007
Making Mouse Models That Reflect Human Immune Responses.
Lili Tao (2017)
10.1073/pnas.1404402111
Rescuing US biomedical research from its systemic flaws
Bruce M. Alberts (2014)
10.1038/nrd1830
Infectious disease: Unravelling SARS lethality
Alexandra Flemming (2005)
10.1371/journal.pbio.1001863
Distinguishing between Exploratory and Confirmatory Preclinical Research Will Improve Translation
Jonathan Kimmelman (2014)
10.1016/j.cmet.2016.08.006
Never Waste a Good Crisis: Confronting Reproducibility in Translational Research.
Daniel J Drucker (2016)
10.1016/j.immuni.2015.06.011
Passenger Mutations Confound Interpretation of All Genetically Modified Congenic Mice.
Tom Vanden Berghe (2015)
10.1016/0031-9384(86)90112-5
Age-related changes in learning and memory in the senescence-accelerated mouse (SAM)
Masaomi Miyamoto (1986)
10.1007/s00401-016-1662-x
Alzheimer’s disease: experimental models and reality
Eleanor Drummond (2016)
10.1016/S0531-5565(02)00160-2
The neurobiology of memory changes in normal aging
Cynthia A. Erickson (2003)
10.1021/acschemneuro.6b00278
Disease-Modifying Effects of M1 Muscarinic Acetylcholine Receptor Activation in an Alzheimer's Disease Mouse Model.
Evan P Lebois (2017)
10.1038/npp.2010.104
Modes and Models of Forebrain Cholinergic Neuromodulation of Cognition
Michael E. Hasselmo (2011)
10.1016/S0306-4522(97)00507-1
Co-injection of β-amyloid with ibotenic acid induces synergistic loss of rat hippocampal neurons
Kiyoshi Morimoto (1998)
10.1016/B978-0-12-809468-6.00040-1
Animal Models of Alzheimer's Disease
Morgan Newman (2017)
10.1126/science.aao4827
Secreted amyloid-β precursor protein functions as a GABABR1a ligand to modulate synaptic transmission
Heather C Rice (2019)
10.1001/archneur.1997.00550160091022
Effects of xanomeline, a selective muscarinic receptor agonist, on cognitive function and behavioral symptoms in Alzheimer disease.
Neil Clayton Bodick (1997)
10.1007/978-3-540-37652-1_2
The history of Alois Alzheimer’s first case Auguste D.
Konrad Maurer (2006)
10.3233/ADR-170049
Neonatal Neurodegeneration in Alzheimer’s Disease Transgenic Mouse Model
Aise Rumeysa Mazi (2018)
10.3389/fnagi.2018.00250
The McGill Transgenic Rat Model of Alzheimer's Disease Displays Cognitive and Motor Impairments, Changes in Anxiety and Social Behavior, and Altered Circadian Activity
Tomáš Petrášek (2018)
10.1523/JNEUROSCI.3279-05.2005
Age-Dependent Neurofibrillary Tangle Formation, Neuron Loss, and Memory Impairment in a Mouse Model of Human Tauopathy (P301L)
Martin Ramsden (2005)
10.3233/JAD-2010-1349
A novel transgenic rat model with a full Alzheimer's-like amyloid pathology displays pre-plaque intracellular amyloid-beta-associated cognitive impairment.
Wanda C Leon (2010)
10.1172/JCI78464
Cross-species translation of the Morris maze for Alzheimer's disease.
Katherine L. Possin (2016)
10.1016/0006-8993(95)01050-X
Behavioral and neurobiological alterations induced by the immunotoxin 192-IgG-saporin: cholinergic and non-cholinergic effects following i.c.v. injection
Thomas Joseph Walsh (1995)
10.1371/journal.pbio.1001609
Evaluation of Excess Significance Bias in Animal Studies of Neurological Diseases
Konstantinos K Tsilidis (2013)
10.1007/s00401-018-1918-8
Questions concerning the role of amyloid-β in the definition, aetiology and diagnosis of Alzheimer’s disease
Gary P. Morris (2018)
10.1186/2051-5960-2-61
Intracellular Aβ pathology and early cognitive impairments in a transgenic rat overexpressing human amyloid precursor protein: a multidimensional study
M Florencia Iulita (2014)
10.1523/JNEUROSCI.20-17-06452.2000
Aging Increased Amyloid Peptide and Caused Amyloid Plaques in Brain of Old APP/V717I Transgenic Mice by a Different Mechanism than Mutant Presenilin1
Ilse Dewachter (2000)
10.1016/j.drudis.2011.12.020
Can the flow of medicines be improved? Fundamental pharmacokinetic and pharmacological principles toward improving Phase II survival.
P. Morgan (2012)
10.1111/j.0887-378X.2004.00319.x
Cognition-enhancing drugs.
Maxwell J. Mehlman (2004)
10.1126/science.1566067
Alzheimer's disease: the amyloid cascade hypothesis.
J. A. Hardy (1992)
10.1016/j.molmed.2017.03.008
TREM2, Microglia, and Neurodegenerative Diseases.
Felix L. Yeh (2017)
10.1016/B978-0-12-804725-5.00002-1
Experimental Planning and Execution
Kevin Mullane (2018)
10.1126/scitranslmed.aac9888
Data gaps limit the translational potential of preclinical research
Robin J Kleiman (2016)
10.1126/sciadv.aau3333
Porphyromonas gingivalis in Alzheimer’s disease brains: Evidence for disease causation and treatment with small-molecule inhibitors
Stephen S Dominy (2019)
10.1002/ana.24188
A Critique of the Drug Discovery and Phase 3 Clinical Programs Targeting the Amyloid Hypothesis for Alzheimer Disease
Eric H. Karran (2014)
10.1242/dmm.024547
Using the mouse to model human disease: increasing validity and reproducibility
Monica J. Justice (2016)
10.1016/S0006-8993(98)01258-X
Behavioral phenotyping of transgenic and knockout mice: experimental design and evaluation of general health, sensory functions, motor abilities, and specific behavioral tests
Jacqueline N. Crawley (1999)
10.1124/jpet.102.041616
The Cholinergic Hypothesis of Age and Alzheimer's Disease-Related Cognitive Deficits: Recent Challenges and Their Implications for Novel Drug Development
Alvin V. Terry (2003)
10.1016/j.lfs.2014.05.017
Animal models of dementia and cognitive dysfunction.
Neha (2014)
10.1186/1471-2202-9-28
Development of transgenic rats producing human β-amyloid precursor protein as a model for Alzheimer's disease: Transgene and endogenous APP genes are regulated tissue-specifically
Cansu Agca (2007)
10.1136/BMJOS-2018-000002
Revision of the ARRIVE guidelines: rationale and scope
Nathalie Percie du Sert (2018)
10.1016/j.ddtec.2012.04.001
Animal models of Alzheimer's disease and drug development.
Bart E. Laurijssens (2013)
10.1037/h0077579
Memory deficits associated with senescence: a neurophysiological and behavioral study in the rat.
Carol A. Barnes (1979)
10.2147/CLEP.S37929
Clinical epidemiology of Alzheimer’s disease: assessing sex and gender differences
Michelle M. Mielke (2014)
10.1038/509282a
Policy: NIH to balance sex in cell and animal studies.
Janine A Clayton (2014)
10.1007/s00213-008-1365-7
Pharmaceutical treatment for cognitive deficits in Alzheimer’s disease and other neurodegenerative conditions: exploring new territory using traditional tools and established maps
Raymond T. Bartus (2008)
10.1038/542409a
No publication without confirmation
Jeffrey S. Mogil (2017)
10.1038/297681a0
Place navigation impaired in rats with hippocampal lesions
Richard G. M. Morris (1982)
10.1016/j.bcp.2017.12.011
How often should we expect to be wrong? Statistical power, P values, and the expected prevalence of false discoveries
Michael J. Marino (2018)
10.1093/ijnp/pyx012
Discontinuation, Efficacy, and Safety of Cholinesterase Inhibitors for Alzheimer’s Disease: a Meta-Analysis and Meta-Regression of 43 Randomized Clinical Trials Enrolling 16 106 Patients
Lídia Blanco-Silvente (2017)
10.1016/B978-0-12-802810-0.00012-X
Rodent Models for Alzheimer’s Disease in Drug Discovery
Jeannie E. Barrett (2017)
10.1073/pnas.94.24.13287
Two amyloid precursor protein transgenic mouse models with Alzheimer disease-like pathology.
Christine Sturchler-Pierrat, (1997)
10.1074/jbc.274.10.6483
Early Phenotypic Changes in Transgenic Mice That Overexpress Different Mutants of Amyloid Precursor Protein in Brain*
Dieder Moechars (1999)
10.1046/j.1471-4159.2003.01879.x
Hyperphosphorylation and aggregation of tau in mice expressing normal human tau isoforms.
Cathy Andorfer (2003)
10.1016/j.neuron.2017.02.042
Elucidating the Role of TREM2 in Alzheimer’s Disease
Jason D Ulrich (2017)
10.1016/S2215-0366(15)00004-8
Pharmacological cognitive enhancement: treatment of neuropsychiatric disorders and lifestyle use by healthy people.
Barbara J. Sahakian (2015)
10.1038/nm0198-097
Accelerated Alzheimer-type phenotype in transgenic mice carrying both mutant amyloid precursor protein and presenilin 1 transgenes
Leigh A. Holcomb (1998)
10.1038/s41562-017-0189-z
Redefine statistical significance
Daniel J. Benjamin (2017)
10.1097/FBP.0000000000000300
A second wind for the cholinergic system in Alzheimer’s therapy
Vincent Douchamps (2017)
10.1126/sciadv.aav1966
High-throughput screening for selective appetite modulators: A multibehavioral and translational drug discovery strategy
Josua Jordi (2018)
10.1046/j.1365-2362.1998.00393.x
Scopolamine model of dementia: electroencephalogram findings and cognitive performance.
Ulrike Ebert (1998)
10.1016/0166-4328(93)90127-C
A primate model of Alzheimer's disease
Gary L. Wenk (1993)
10.1074/jbc.R112.407668
The Nicotinic Acetylcholine Receptor: The Founding Father of the Pentameric Ligand-gated Ion Channel Superfamily*
Jean-Pierre Changeux (2012)
10.1037/0735-7044.107.4.618
Severity of spatial learning impairment in aging: development of a learning index for performance in the Morris water maze.
M D Gallagher (1993)
10.1016/j.brainresbull.2015.12.003
Toward more predictive genetic mouse models of Alzheimer's disease
Kristen D. Onos (2016)
10.1016/j.bcp.2018.09.026
Alzheimer's disease (AD) therapeutics – 1: Repeated clinical failures continue to question the amyloid hypothesis of AD and the current understanding of AD causality
Kevin Mullane (2018)
10.1016/0169-328X(91)90108-A
Increased biosynthesis of Alzheimer amyloid precursor protein in the cerebral cortex of rats with lesions of the nucleus basalis of Meynert.
William C. Wallace (1991)
10.1016/j.celrep.2017.12.066
Diverse Brain Myeloid Expression Profiles Reveal Distinct Microglial Activation States and Aspects of Alzheimer's Disease Not Evident in Mouse Models.
Brad A. Friedman (2018)
10.1007/s00401-015-1392-5
Nucleus basalis of Meynert revisited: anatomy, history and differential involvement in Alzheimer’s and Parkinson’s disease
Alan King Lun Liu (2015)
10.1016/j.bcp.2014.01.011
Behavioral assays with mouse models of Alzheimer's disease: practical considerations and guidelines.
Daniela Puzzo (2014)
10.3389/fnagi.2015.00234
Connectivity of Pathology: The Olfactory System as a Model for Network-Driven Mechanisms of Alzheimer’s Disease Pathogenesis
Katherine H. Franks (2015)
10.1016/j.jalz.2018.02.018
NIA-AA Research Framework: Toward a biological definition of Alzheimer’s disease
Clifford R. Jack (2018)
10.1001/jamaneurol.2015.2952
Association Between Olfactory Dysfunction and Amnestic Mild Cognitive Impairment and Alzheimer Disease Dementia.
Rosebud O. Roberts (2016)
10.1016/j.brainres.2014.02.007
Neuroprotective effect of nobiletin on cerebral ischemia–reperfusion injury in transient middle cerebral artery-occluded rats
Nodoka Yasuda (2014)
10.1016/j.tips.2016.01.008
Drug Tolerance: A Known Unknown in Translational Neuroscience.
Anton Bespalov (2016)
10.1007/BF02245257
Behavioral screening for cognition enhancers: from indiscriminate to valid testing: Part II
Martin Sarter (2005)
10.1126/science.274.5284.99
Correlative Memory Deficits, Aβ Elevation, and Amyloid Plaques in Transgenic Mice
Karen K. Hsiao (1996)
10.1186/s13195-015-0153-y
The need for thorough phase II studies in medicines development for Alzheimer’s disease
Julian A. Gray (2015)
10.1126/science.7046051
The cholinergic hypothesis of geriatric memory dysfunction.
Raymond T. Bartus (1982)
10.1016/0024-3205(96)00185-3
The AF64A model of cholinergic hypofunction: an update.
Israel Hanin (1996)
10.2307/3350070
From senility to Alzheimer's disease: the rise of the Alzheimer's disease movement.
Patrick J. Fox (1989)
10.1038/nrd.2018.234
The implications of target saturation for the use of drug–target residence time
Wilhelmus E. A. de Witte (2018)
10.1186/1750-1326-8-37
Modeling Alzheimer’s disease in transgenic rats
Sonia Do Carmo (2013)
10.1016/j.neubiorev.2004.10.006
Meta-analysis of sex differences in rodent models of learning and memory: a review of behavioral and biological data
Zachariah Jonasson (2005)
10.1016/j.coph.2019.01.004
The de-Alzheimerization of age-related dementias: implications for drug targets and approaches to effective therapeutics.
Kevin Mullane (2019)
10.1016/0165-0173(94)90011-6
Piracetam and other structurally related nootropics
Alex Haahr Gouliaev (1994)
10.1016/j.bcp.2018.09.027
Alzheimer's disease (AD) therapeutics - 2: Beyond amyloid - Re-defining AD and its causality to discover effective therapeutics.
Kevin Mullane (2018)
10.1016/S0140-6736(17)31363-6
Dementia prevention, intervention, and care
Gill Livingston (2017)
10.1016/j.neurobiolaging.2012.02.027
Animal systems in the development of treatments for Alzheimer's disease: challenges, methods, and implications
Jonathan J. Sabbagh (2013)
10.1016/j.biopsych.2017.10.023
(−)-P7C3-S243 Protects a Rat Model of Alzheimer’s Disease From Neuropsychiatric Deficits and Neurodegeneration Without Altering Amyloid Deposition or Reactive Glia
Jaymie R. Voorhees (2017)
10.1016/j.bcp.2007.06.033
Neuronal nicotinic receptors: a perspective on two decades of drug discovery research.
Stephen Arneric (2007)
Pharmacological models in Alzheimer's disease research
Christian Gilles (2000)
10.1016/j.drudis.2014.10.015
Improving the predictive value of interventional animal models data.
Caroline J. Zeiss (2015)
10.1016/j.trci.2017.04.005
Phase II clinical trials of anti–amyloid β antibodies: When is enough, enough?
Michael A. Gold (2017)
10.1186/s40478-018-0603-4
Alzheimer’s associated amyloid and tau deposition co-localizes with a homeostatic myelin repair pathway in two mouse models of post-stroke mixed dementia
Thuy-Vi V. Nguyen (2018)
10.2174/1567205043332117
Lesions and dysfunctions of the nucleus basalis as Alzheimer's disease models: general and critical overview and analysis of the long-term changes in several excitotoxic models.
A. Toledano (2004)
10.1093/cercor/bhv332
Intraneuronal Amyloid Beta Accumulation Disrupts Hippocampal CRTC1‐Dependent Gene Expression and Cognitive Function in a Rat Model of Alzheimer Disease
Edward N Wilson (2017)
10.1371/journal.pone.0147733
A Comprehensive Behavioral Test Battery to Assess Learning and Memory in 129S6/Tg2576 Mice
Andrea Wolf (2016)
10.1186/s12868-016-0281-8
Presenilin 1 transgene addition to amyloid precursor protein overexpressing transgenic rats increases amyloid beta 42 levels and results in loss of memory retention
Cansu Agca (2016)
10.3233/JAD-142208
Systematic Review of the Relationship between Amyloid-β Levels and Measures of Transgenic Mouse Cognitive Deficit in Alzheimer’s Disease
Avery M. Foley (2015)
10.1038/s41582-018-0116-6
A critical appraisal of amyloid-β-targeting therapies for Alzheimer disease
Francesco Panza (2019)
10.1016/S0091-3057(01)00747-X
Cholinergic blockade impairs performance in operant DNMTP in two inbred strains of mice
Nuria Estapé (2002)
10.1038/s41582-018-0072-1
TREM2 — a key player in microglial biology and Alzheimer disease
Tyler K Ulland (2018)
10.1016/j.ejphar.2013.03.051
Ginsenoside Rg1 attenuates okadaic acid induced spatial memory impairment by the GSK3β/tau signaling pathway and the Aβ formation prevention in rats.
Xiu-yun Song (2013)
10.1002/prp2.162
Helping to drive the robustness of preclinical research – the assay capability tool
Katrina Gore (2015)
10.3389/fgene.2014.00088
Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models
Scott J. Webster (2014)
10.3389/fnagi.2018.00324
Corroboration of a Major Role for Herpes Simplex Virus Type 1 in Alzheimer’s Disease
R. F. Itzhaki (2018)
10.1186/alzrt171
Modeling Alzheimer's disease with non-transgenic rat models
Laurent Lecanu (2013)
10.1371/journal.pone.0195469
Memory deficiency, cerebral amyloid angiopathy, and amyloid-β plaques in APP+PS1 double transgenic rat model of Alzheimer’s disease
Diana Klakotskaia (2018)
10.1523/JNEUROSCI.1202-06.2006
Intraneuronal β-Amyloid Aggregates, Neurodegeneration, and Neuron Loss in Transgenic Mice with Five Familial Alzheimer's Disease Mutations: Potential Factors in Amyloid Plaque Formation
Holly Oakley (2006)
10.1093/hmg/ddh199
Independent effects of APOE on cholesterol metabolism and brain Abeta levels in an Alzheimer disease mouse model.
Karen M. Mann (2004)
10.1016/S0896-6273(03)00434-3
Triple-Transgenic Model of Alzheimer's Disease with Plaques and Tangles Intracellular Aβ and Synaptic Dysfunction
Salvatore Oddo (2003)
10.1073/pnas.90.18.8712
Amyloid precursor protein in the cerebral cortex is rapidly and persistently induced by loss of subcortical innervation.
William Clay Wallace (1993)
10.1155/2013/215798
Protective Effects of p38 MAPK Inhibitor SB202190 against Hippocampal Apoptosis and Spatial Learning and Memory Deficits in a Rat Model of Vascular Dementia
Shen Lin Yang (2013)
10.1074/jbc.M010977200
Mutant Presenilins Disturb Neuronal Calcium Homeostasis in the Brain of Transgenic Mice, Decreasing the Threshold for Excitotoxicity and Facilitating Long-term Potentiation*
Ilka Schneider (2001)
10.1002/0471140856.tx1118s63
Methods to measure olfactory behavior in mice.
Junhui Zou (2015)
10.1016/j.drudis.2016.02.012
Animal disease models for drug screening: the elephant in the room?
Takashi Tsukamoto (2016)
10.1016/j.cell.2015.12.056
The Cellular Phase of Alzheimer’s Disease
Bart de Strooper (2016)
10.1001/archneur.1976.00500040001001
Editorial: The prevalence and malignancy of Alzheimer disease. A major killer.
Robert Katzman. (1976)
10.1016/j.ejphar.2014.11.047
Highthroughtput analysis of behavior for drug discovery
Vadim Alexandrov (2015)
10.1016/0166-2236(89)90054-4
The molecular basis of muscarinic receptor diversity
Tom I. Bonner (1989)
10.1371/journal.pbio.1000412
Improving Bioscience Research Reporting: The ARRIVE Guidelines for Reporting Animal Research
Carol Kilkenny (2010)
10.1096/fj.201601352
Lost Dollars Threaten Research in Public Academic Health Centers.
H. R. Fox Bourne (2017)
10.1037/0735-7044.112.5.1199
Intracerebroventricular administration of streptozotocin causes long-term diminutions in learning and memory abilities and in cerebral energy metabolism in adult rats.
Heinrich Lannert (1998)
10.1016/j.neurobiolaging.2003.09.008
APP processing and amyloid deposition in mice haplo-insufficient for presenilin 1
Joanna L. Jankowsky (2004)
10.1146/annurev-animal-022114-110829
Animal models of aging research: implications for human aging and age-related diseases.
Sarah Jayne Mitchell (2015)
10.1186/alzrt90
Accelerating drug discovery for Alzheimer's disease: best practices for preclinical animal studies
Diana W. Shineman (2011)
10.1038/373523a0
Alzheimer-type neuropathology in transgenic mice overexpressing V717F β-amyloid precursor protein
D. Games (1995)
10.1080/17482960701856300
Design, power, and interpretation of studies in the standard murine model of ALS
Sean Scott (2008)
10.1016/j.jalz.2016.07.001
Guidelines to improve animal study design and reproducibility for Alzheimer's disease and related dementias: For funders and researchers
Heather M Snyder (2016)
10.1038/srep41120
Potential molecular consequences of transgene integration: The R6/2 mouse example
Jessie C. Jacobsen (2017)
10.1038/507423a
Preclinical research: Make mouse studies work.
Steve Perrin (2014)
10.1186/2051-5960-1-62
The airbag problem–a potential culprit for bench-to-bedside translational efforts: relevance for Alzheimer’s disease
Dimitrije N. Krstic (2013)
10.1212/WNL.0000000000000438
β-Amyloidosis and neurodegeneration in Alzheimer disease
David S. Knopman (2014)
10.1016/j.bbr.2016.05.007
Transcriptional signatures of brain aging and Alzheimer’s disease: What are our rodent models telling us?
Kendra Hargis (2017)
10.1186/1744-9081-5-11
Evaluation of animal models of neurobehavioral disorders
F. Josef van der Staay (2008)
10.1002/ebm2.15
From a mouse: systematic analysis reveals limitations of experiments testing interventions in Alzheimer's disease mouse models
K.J. Egan (2016)
10.1172/JCI97509
Blood will out: vascular contributions to Alzheimer’s disease
Sidney Strickland (2018)
10.1093/jnen/nlw047
Gender Differences in Alzheimer Disease: Brain Atrophy, Histopathology Burden, and Cognition
Jessica Filon (2016)
10.1111/j.1476-5381.2011.01299.x
Animal models in the drug discovery pipeline for Alzheimer's disease
Debby Van Dam (2011)
10.1523/JNEUROSCI.20-11-04050.2000
High-Level Neuronal Expression of Aβ1–42 in Wild-Type Human Amyloid Protein Precursor Transgenic Mice: Synaptotoxicity without Plaque Formation
Lennart Mucke (2000)
10.1016/j.bcp.2013.08.006
Animal models of human disease: challenges in enabling translation.
Paul McGonigle (2014)
10.1016/j.jalz.2018.06.3040
The antimicrobial protection hypothesis of Alzheimer's disease
Robert D. Moir (2018)
10.15252/embj.201797397
APP mouse models for Alzheimer's disease preclinical studies
Hiroki Sasaguri (2017)
10.1016/S0197-4580(00)00116-0
Chronic cerebrovascular ischemia in aged rats: effects on brain metabolic capacity and behavior☆
Amy Čada (2000)
10.1016/0166-4328(88)90157-X
A new one-trial test for neurobiological studies of memory in rats. 1: Behavioral data
Abdelkader Ennaceur (1988)
10.1016/j.neubiorev.2015.09.002
The problem of genotype and sex differences in life expectancy in transgenic AD mice
Eric A. Rae (2015)
10.3389/fnbeh.2014.00321
Longitudinal analysis of the behavioral phenotype in a novel transgenic rat model of early stages of Alzheimer's disease
Pablo Galeano (2014)



This paper is referenced by
10.1371/journal.pone.0226176
Menagerie: A text-mining tool to support animal-human translation in neurodegeneration research
Caroline J. Zeiss (2019)
10.1038/s41684-019-0465-9
Modeling neurological disease using human stem cell-derived microglia-like cells transplanted into rodent brains
Fadi Jacob (2020)
10.3389/fnagi.2019.00324
Perturbations of Ubiquitin-Proteasome-Mediated Proteolysis in Aging and Alzheimer’s Disease
Ashok N. Hegde (2019)
10.1093/gerona/glz298
Bring Back the Rat!
Christy S. Carter (2020)
10.1101/2020.05.08.082784
E2F4 as a single multifactorial target against Alzheimer’s disease
Noelia López-Sánchez (2020)
10.1007/s00441-020-03198-6
Utility of spontaneous animal models of Alzheimer’s disease in preclinical efficacy studies
Caroline J. Zeiss (2020)
10.1016/j.neures.2020.01.002
Oscillotherapeutics – Time-targeted interventions in epilepsy and beyond
Yuichi Takeuchi (2020)
10.1016/j.cbi.2020.109019
An in vitro study on the interaction of the anti-Alzheimer drug rivastigmine with human erythrocytes.
Pablo A. Zambrano (2020)
10.1002/CPNS.81
Overview of Transgenic Mouse Models for Alzheimer's Disease.
Ariana Myers (2019)
10.1016/bs.pbr.2019.03.009
Nanowired delivery of cerebrolysin with neprilysin and p-Tau antibodies induces superior neuroprotection in Alzheimer's disease.
Hari Shanker Sharma (2019)
10.1016/j.bcp.2020.113945
Alzheimer's disease beyond amyloid: can the repetitive failures of amyloid-targeted therapeutics inform future approaches to dementia drug discovery?
Kevin Mullane (2020)
10.3390/molecules24081519
Natural Products in Alzheimer’s Disease Therapy: Would Old Therapeutic Approaches Fix the Broken Promise of Modern Medicines?
Solomon Habtemariam (2019)
10.3233/JAD-190602
Calcilytic NPS 2143 Reduces Amyloid Secretion and Increases sAβPPα Release from PSEN1 Mutant iPSC-Derived Neurons
M C Lo Giudice (2019)
10.1038/s41573-020-0065-9
Leveraging preclinical models for the development of Alzheimer disease therapeutics
Kimberly Scearce-Levie (2020)
10.1016/j.tips.2019.06.003
Insights into Computational Drug Repurposing for Neurodegenerative Disease.
Manish D. Paranjpe (2019)
10.1016/j.trci.2019.04.002
A 24-week double-blind placebo-controlled study of the efficacy and safety of the AMPA modulator S47445 in patients with mild to moderate Alzheimer's disease and depressive symptoms
Katy Bernard (2019)
10.3389/fphar.2019.00778
Targeting Synaptic Plasticity in Experimental Models of Alzheimer’s Disease
Dalila Mango (2019)
10.1016/j.ejphar.2019.172524
Are some animal models more equal than others? A case study on the translational value of animal models of efficacy for Alzheimer''s disease.
Désirée H Veening-Griffioen (2019)
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