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

Kevin Mullane, M. 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
10.1002/(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
D. Diamond (1999)
10.1038/nprot.2006.116
Morris water maze: procedures for assessing spatial and related forms of learning and memory
C. Vorhees (2006)
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
H. Wang (2009)
10.1016/S0531-5565(96)00036-8
Senescence-accelerated mouse (SAM): A novel murine model of senescence
Toshio Takeda (1997)
10.3233/ADR-170049
Neonatal Neurodegeneration in Alzheimer’s Disease Transgenic Mouse Model
Aise Rumeysa Mazi (2018)
10.1007/978-3-540-37652-1_2
The history of Alois Alzheimer’s first case Auguste D.
K. Maurer (2006)
10.1001/ARCHNEUR.1997.00550160091022
Effects of xanomeline, a selective muscarinic receptor agonist, on cognitive function and behavioral symptoms in Alzheimer disease.
N. Bodick (1997)
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.
X. Song (2013)
10.1038/s41582-018-0116-6
A critical appraisal of amyloid-β-targeting therapies for Alzheimer disease
F. Panza (2019)
10.1002/prp2.162
Helping to drive the robustness of preclinical research – the assay capability tool
Katrina Gore (2015)
10.1016/S0091-3057(01)00747-X
Cholinergic blockade impairs performance in operant DNMTP in two inbred strains of mice
N. Estapé (2002)
10.1038/s41582-018-0072-1
TREM2 — a key player in microglial biology and Alzheimer disease
Tyler K Ulland (2018)
10.2147/CLEP.S37929
Clinical epidemiology of Alzheimer’s disease: assessing sex and gender differences
M. Mielke (2014)
10.1037/h0077579
Memory deficits associated with senescence: a neurophysiological and behavioral study in the rat.
C. A. Barnes (1979)
10.1016/j.ddtec.2012.04.001
Animal models of Alzheimer's disease and drug development.
Bart E. Laurijssens (2013)
10.1038/509282A
Policy: NIH to balance sex in cell and animal studies.
J. 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
R. Bartus (2008)
10.1073/pnas.1404402111
Rescuing US biomedical research from its systemic flaws
B. Alberts (2014)
10.1038/nrd1830
Infectious disease: Unravelling SARS lethality
Alexandra Flemming (2005)
10.1016/j.it.2016.12.007
Making Mouse Models That Reflect Human Immune Responses.
Lili Tao (2017)
10.1126/SCIENCE.1058189
Enhanced Neurofibrillary Degeneration in Transgenic Mice Expressing Mutant Tau and APP
J. Lewis (2001)
10.1523/JNEUROSCI.3672-12.2013
A Transgenic Alzheimer Rat with Plaques, Tau Pathology, Behavioral Impairment, Oligomeric Aβ, and Frank Neuronal Loss
R. Cohen (2013)
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
H. Rice (2019)
10.1021/acschemneuro.6b00278
Disease-Modifying Effects of M1 Muscarinic Acetylcholine Receptor Activation in an Alzheimer's Disease Mouse Model.
E. Lebois (2017)
10.1016/S0306-4522(97)00507-1
Co-injection of β-amyloid with ibotenic acid induces synergistic loss of rat hippocampal neurons
K. Morimoto (1998)
10.1038/npp.2010.104
Modes and Models of Forebrain Cholinergic Neuromodulation of Cognition
M. Hasselmo (2011)
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
M. 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)
10.1038/542409a
No publication without confirmation
J. Mogil (2017)
10.1016/B978-0-12-802810-0.00012-X
Rodent Models for Alzheimer’s Disease in Drug Discovery
J. Barrett (2017)
10.1038/297681a0
Place navigation impaired in rats with hippocampal lesions
R. Morris (1982)
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
J. Crawley (1999)
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
C. Agca (2007)
10.1016/j.lfs.2014.05.017
Animal models of dementia and cognitive dysfunction.
Neha (2014)
10.1242/dmm.024547
Using the mouse to model human disease: increasing validity and reproducibility
M. Justice (2016)
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
A. Terry (2003)
10.1136/BMJOS-2018-000002
Revision of the ARRIVE guidelines: rationale and scope
Nathalie Percie du Sert (2018)
10.1016/j.cmet.2016.08.006
Never Waste a Good Crisis: Confronting Reproducibility in Translational Research.
D. Drucker (2016)
10.1016/S0531-5565(02)00160-2
The neurobiology of memory changes in normal aging
C. Erickson (2003)
10.1016/0031-9384(86)90112-5
Age-related changes in learning and memory in the senescence-accelerated mouse (SAM)
Masaomi Miyamoto (1986)
10.1371/journal.pbio.1001863
Distinguishing between Exploratory and Confirmatory Preclinical Research Will Improve Translation
J. Kimmelman (2014)
10.1007/s00401-016-1662-x
Alzheimer’s disease: experimental models and reality
Eleanor Drummond (2016)
10.1016/j.immuni.2015.06.011
Passenger Mutations Confound Interpretation of All Genetically Modified Congenic Mice.
T. Vanden Berghe (2015)
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. F. Iulita (2014)
10.1111/J.0887-378X.2004.00319.X
Cognition-enhancing drugs.
M. Mehlman (2004)
10.1371/journal.pbio.1001609
Evaluation of Excess Significance Bias in Animal Studies of Neurological Diseases
K. 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)
10.1523/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
I. 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)
10.3233/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.
W. Leon (2010)
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)
M. Ramsden (2005)
10.1172/JCI78464
Cross-species translation of the Morris maze for Alzheimer's disease.
K. 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
T. J. Walsh (1995)
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)
10.1007/s00401-015-1392-5
Nucleus basalis of Meynert revisited: anatomy, history and differential involvement in Alzheimer’s and Parkinson’s disease
A. K. L. Liu (2015)
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)
10.1037/0735-7044.107.4.618
Severity of spatial learning impairment in aging: development of a learning index for performance in the Morris water maze.
M. Gallagher (1993)
10.1016/j.brainresbull.2015.12.003
Toward more predictive genetic mouse models of Alzheimer's disease
Kristen D. Onos (2016)
10.1016/0169-328X(91)90108-A
Increased biosynthesis of Alzheimer amyloid precursor protein in the cerebral cortex of rats with lesions of the nucleus basalis of Meynert.
W. Wallace (1991)
10.1126/science.1566067
Alzheimer's disease: the amyloid cascade hypothesis.
J. 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
R. Kleiman (2016)
10.1002/ana.24188
A Critique of the Drug Discovery and Phase 3 Clinical Programs Targeting the Amyloid Hypothesis for Alzheimer Disease
E. Karran (2014)
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)
10.1037/0735-7044.112.5.1199
Intracerebroventricular administration of streptozotocin causes long-term diminutions in learning and memory abilities and in cerebral energy metabolism in adult rats.
H. Lannert (1998)
10.1096/fj.201601352
Lost Dollars Threaten Research in Public Academic Health Centers
H. Bourne (2017)
10.1371/journal.pbio.1000412
Improving Bioscience Research Reporting: The ARRIVE Guidelines for Reporting Animal Research
C. Kilkenny (2010)
10.1038/373523a0
Alzheimer-type neuropathology in transgenic mice overexpressing V717F β-amyloid precursor protein
D. Games (1995)
10.1016/j.neurobiolaging.2003.09.008
APP processing and amyloid deposition in mice haplo-insufficient for presenilin 1
J. Jankowsky (2004)
10.1186/alzrt90
Accelerating drug discovery for Alzheimer's disease: best practices for preclinical animal studies
D. Shineman (2011)
10.1146/annurev-animal-022114-110829
Animal models of aging research: implications for human aging and age-related diseases.
S. Mitchell (2015)
10.1016/j.jalz.2018.02.018
NIA-AA Research Framework: Toward a biological definition of Alzheimer’s disease
C. Jack (2018)
10.1001/jamaneurol.2015.2952
Association Between Olfactory Dysfunction and Amnestic Mild Cognitive Impairment and Alzheimer Disease Dementia.
R. Roberts (2016)
10.1016/j.tips.2016.01.008
Drug Tolerance: A Known Unknown in Translational Neuroscience.
Anton Bespalov (2016)
10.1016/j.bcp.2014.01.011
Behavioral assays with mouse models of Alzheimer's disease: practical considerations and guidelines.
D. Puzzo (2014)
10.1016/j.brainres.2014.02.007
Neuroprotective effect of nobiletin on cerebral ischemia–reperfusion injury in transient middle cerebral artery-occluded rats
N. Yasuda (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)
10.1212/WNL.0000000000000438
β-Amyloidosis and neurodegeneration in Alzheimer disease
D. Knopman (2014)
10.1186/1744-9081-5-11
Evaluation of animal models of neurobehavioral disorders
F. J. van der Staay (2008)
10.1038/srep41120
Potential molecular consequences of transgene integration: The R6/2 mouse example
J. C. Jacobsen (2017)
10.1038/507423A
Preclinical research: Make mouse studies work.
S. Perrin (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)
10.1186/2051-5960-1-62
The airbag problem–a potential culprit for bench-to-bedside translational efforts: relevance for Alzheimer’s disease
D. Krstic (2013)
10.1080/17482960701856300
Design, power, and interpretation of studies in the standard murine model of ALS
S. 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
H. Snyder (2016)
10.1074/jbc.R112.407668
The Nicotinic Acetylcholine Receptor: The Founding Father of the Pentameric Ligand-gated Ion Channel Superfamily*
J. Changeux (2012)
10.1016/0166-4328(93)90127-C
A primate model of Alzheimer's disease
G. Wenk (1993)
10.1038/s41562-017-0189-z
Redefine statistical significance
Daniel J. Benjamin (2017)
10.1038/NM0198-097
Accelerated Alzheimer-type phenotype in transgenic mice carrying both mutant amyloid precursor protein and presenilin 1 transgenes
L. Holcomb (1998)
10.1126/sciadv.aav1966
High-throughput screening for selective appetite modulators: A multibehavioral and translational drug discovery strategy
J. Jordi (2018)
10.1046/j.1365-2362.1998.00393.x
Scopolamine model of dementia: electroencephalogram findings and cognitive performance
Ebert (1998)
10.1097/FBP.0000000000000300
A second wind for the cholinergic system in Alzheimer’s therapy
V. Douchamps (2017)
10.1038/nrd.2018.234
The implications of target saturation for the use of drug–target residence time
W. E. A. D. Witte (2018)
10.1126/science.7046051
The cholinergic hypothesis of geriatric memory dysfunction.
R. Bartus (1982)
10.2307/3350070
From senility to Alzheimer's disease: the rise of the Alzheimer's disease movement.
P. Fox (1989)
10.1186/s13195-015-0153-y
The need for thorough phase II studies in medicines development for Alzheimer’s disease
J. Gray (2015)
10.1007/BF02245257
Behavioral screening for cognition enhancers: from indiscriminate to valid testing: Part II
M. Sarter (2005)
10.1126/science.274.5284.99
Correlative Memory Deficits, Aβ Elevation, and Amyloid Plaques in Transgenic Mice
K. Hsiao (1996)
10.1186/1750-1326-8-37
Modeling Alzheimer’s disease in transgenic rats
S. Do Carmo (2013)
10.1016/0024-3205(96)00185-3
The AF64A model of cholinergic hypofunction: an update.
I. Hanin (1996)
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/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)
10.1016/0165-0173(94)90011-6
Piracetam and other structurally related nootropics
A. H. Gouliaev (1994)
10.1016/S0140-6736(17)31363-6
Dementia prevention, intervention, and care
G. Livingston (2017)
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/J.BCP.2007.06.033
Neuronal nicotinic receptors: a perspective on two decades of drug discovery research.
S. Arneric (2007)
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)
10.1074/jbc.274.10.6483
Early Phenotypic Changes in Transgenic Mice That Overexpress Different Mutants of Amyloid Precursor Protein in Brain*
D. Moechars (1999)
10.1016/j.neuron.2017.02.042
Elucidating the Role of TREM2 in Alzheimer’s Disease
J. Ulrich (2017)
10.1016/S2215-0366(15)00004-8
Pharmacological cognitive enhancement: treatment of neuropsychiatric disorders and lifestyle use by healthy people.
B. Sahakian (2015)
10.1073/PNAS.94.24.13287
Two amyloid precursor protein transgenic mouse models with Alzheimer disease-like pathology.
C. Sturchler-Pierrat, (1997)
10.1046/j.1471-4159.2003.01879.x
Hyperphosphorylation and aggregation of tau in mice expressing normal human tau isoforms
C. Andorfer (2003)
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)
10.1371/journal.pone.0147733
A Comprehensive Behavioral Test Battery to Assess Learning and Memory in 129S6/Tg2576 Mice
Andrea Wolf (2016)
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)
10.1016/j.drudis.2014.10.015
Improving the predictive value of interventional animal models data.
C. Zeiss (2015)
10.1016/j.trci.2017.04.005
Phase II clinical trials of anti–amyloid β antibodies: When is enough, enough?
M. Gold (2017)
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)
Pharmacological models in Alzheimer's disease research
C. Gilles (2000)
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)
10.1186/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
T. Nguyen (2018)
10.1016/j.drudis.2016.02.012
Animal disease models for drug screening: the elephant in the room?
T. Tsukamoto (2016)
10.1001/archneur.1976.00500040001001
Editorial: The prevalence and malignancy of Alzheimer disease. A major killer.
R. Katzman (1976)
10.1016/j.cell.2015.12.056
The Cellular Phase of Alzheimer’s Disease
B. Strooper (2016)
10.1016/j.ejphar.2014.11.047
Highthroughtput analysis of behavior for drug discovery
V. Alexandrov (2015)
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*
I. Schneider (2001)
10.1016/0166-2236(89)90054-4
The molecular basis of muscarinic receptor diversity
T. Bonner (1989)
10.1002/0471140856.tx1118s63
Methods to Measure Olfactory Behavior in Mice
Junhui Zou (2015)
10.3389/fnagi.2018.00324
Corroboration of a Major Role for Herpes Simplex Virus Type 1 in Alzheimer’s Disease
R. Itzhaki (2018)
10.1186/alzrt171
Modeling Alzheimer's disease with non-transgenic rat models
L. Lecanu (2013)
10.1073/pnas.90.18.8712
Amyloid precursor protein in the cerebral cortex is rapidly and persistently induced by loss of subcortical innervation.
W. Wallace (1993)
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)
10.1371/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)
10.1016/S0896-6273(03)00434-3
Triple-Transgenic Model of Alzheimer's Disease with Plaques and Tangles Intracellular Aβ and Synaptic Dysfunction
S. Oddo (2003)
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
S. J. Webster (2014)
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)
10.1155/2013/215798
Protective Effects of p38 MAPK Inhibitor SB202190 against Hippocampal Apoptosis and Spatial Learning and Memory Deficits in a Rat Model of Vascular Dementia
S. Yang (2013)
10.1093/jnen/nlw047
Gender Differences in Alzheimer Disease: Brain Atrophy, Histopathology Burden, and Cognition
Jessica Filon (2016)
10.1016/j.jalz.2018.06.3040
The antimicrobial protection hypothesis of Alzheimer's disease
R. Moir (2018)
10.1111/J.1476-5381.2011.01299.X
Animal models in the drug discovery pipeline for Alzheimer's disease.
D. V. Dam (2011)
10.3389/fnbeh.2014.00321
Longitudinal analysis of the behavioral phenotype in a novel transgenic rat model of early stages of Alzheimer's disease
P. Galeano (2014)
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)
10.1016/S0197-4580(00)00116-0
Chronic cerebrovascular ischemia in aged rats: effects on brain metabolic capacity and behavior☆
A. Čada (2000)
10.1172/JCI97509
Blood will out: vascular contributions to Alzheimer’s disease
Sidney Strickland (2018)
10.1016/0166-4328(88)90157-X
A new one-trial test for neurobiological studies of memory in rats. 1: Behavioral data
A. 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)
10.15252/embj.201797397
APP mouse models for Alzheimer's disease preclinical studies
H. Sasaguri (2017)
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
L. Mucke (2000)
10.1016/j.bcp.2013.08.006
Animal models of human disease: challenges in enabling translation.
P. McGonigle (2014)



This paper is referenced by
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/bs.pbr.2019.03.009
Nanowired delivery of cerebrolysin with neprilysin and p-Tau antibodies induces superior neuroprotection in Alzheimer's disease.
H. Sharma (2019)
10.1016/j.nbd.2020.105088
Functional genomics, genetic risk profiling and cell phenotypes in neurodegenerative disease
S. Finkbeiner (2020)
10.1016/j.neures.2020.01.002
Oscillotherapeutics – Time-targeted interventions in epilepsy and beyond
Y. Takeuchi (2020)
10.1038/s41684-019-0465-9
Modeling neurological disease using human stem cell-derived microglia-like cells transplanted into rodent brains
Fadi Jacob (2020)
10.1371/journal.pone.0226176
Menagerie: A text-mining tool to support animal-human translation in neurodegeneration research
C. Zeiss (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
K. Bernard (2019)
10.1016/j.tips.2019.06.003
Insights into Computational Drug Repurposing for Neurodegenerative Disease.
M. Paranjpe (2019)
10.1093/gerona/glz298
Bring Back the Rat!
C. Carter (2020)
10.3390/molecules24081519
Natural Products in Alzheimer’s Disease Therapy: Would Old Therapeutic Approaches Fix the Broken Promise of Modern Medicines?
S. Habtemariam (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)
10.1038/s41573-020-0065-9
Leveraging preclinical models for the development of Alzheimer disease therapeutics
Kimberly Scearce-Levie (2020)
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)
10.3389/fnagi.2019.00324
Perturbations of Ubiquitin-Proteasome-Mediated Proteolysis in Aging and Alzheimer’s Disease
A. Hegde (2019)
10.3390/biom10060870
Secondary Metabolites from Plants Possessing Inhibitory Properties against Beta-Amyloid Aggregation as Revealed by Thioflavin-T Assay and Correlations with Investigations on Transgenic Mouse Models of Alzheimer’s Disease
R. Ștefănescu (2020)
10.1101/2020.05.08.082784
E2F4 as a single multifactorial target against Alzheimer’s disease
N. López-Sánchez (2020)
10.3390/ani10071194
Alzheimer’s Disease, and Breast and Prostate Cancer Research: Translational Failures and the Importance to Monitor Outputs and Impact of Funded Research
Francesca Pistollato (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/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.
D. Veening-Griffioen (2019)
10.3389/fphar.2019.00778
Targeting Synaptic Plasticity in Experimental Models of Alzheimer’s Disease
D. Mango (2019)
10.1136/jim-2020-001297
Alzheimer’s disease: many failed trials, so where do we go from here?
A. Reiss (2020)
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