Cited by 852Alzheimer's disease research and treatmentsCholinesterase and Neurodegenerative DiseasesDementia and Cognitive Impairment Research

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On Neurodegenerative Diseases, Models, and Treatment Strategies: Lessons Learned and Lessons Forgotten a Generation Following the Cholinergic Hypothesis

Bartus, Raymond T.·2000·Experimental Neurology

DOI 10.1006/exnr.2000.7397

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Abstract

Life's Journey If life is indeed a journey, then poetry must be the map that reveals all its topographic possibilitiesellipsis while science is the compass that keeps us from getting lost. -R. T. Bartus, Simple Words for Complex Lives, (c) 1998 In the nearly 20 years since the cholinergic hypothesis was initially formulated, significant progress has been achieved. Initial palliative treatments for Alzheimer's disease (AD) have proven beneficial and have gained FDA approval, the use of animal models for studying AD and other neurodegenerative diseases has achieved wider acceptance, and important insight into the potential causes and pathogenic variables associated with various neurodegenerative diseases continues to increase. This paper reviews the current status of the cholinergic hypothesis in the context of continuing efforts to improve upon existing treatments for AD and explores the role that animal models might continue to play. Using the benefit of hindsight, particular emphasis is placed on an analysis of the approaches, strategies, and assumptions regarding animal models that proved useful in developing the initial treatments and those that did not. Additionally, contemporary issues of AD are discussed within the context of the cholinergic hypothesis, with particular attention given to how they may impact the further refinement of animal models, and the development of even more effective treatments. Finally, arguments are presented that, despite the deserved enthusiasm and optimism for identifying means of halting the pathogenesis of AD, a clear need for more effective palliative treatments will continue, long after successful pathogenic treatments are available. This review, therefore, focuses on issues and experiences intended to: (a) facilitate further development and use of animal models for AD and other neurodegenerative diseases, and (b) accelerate the identification of newer, even more effective treatments.

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Diagnostic and Statistical Manual of Mental Disorders
Williams, J. B. W., & First, M. B. (2013) · Oxford University Press eBooks · doi:10.1093/acrefore/9780199975839.013.104 · Cited by 109,845
The cholinergic hypothesis of geriatric memory dysfunction
Bartus, R. T., Dean, R. L., Beer, B., & Lippa, A. S. (1982) · Science · doi:10.1126/science.7046051 · Cited by 5,545
Self-citation
Alzheimer's Disease and Senile Dementia: Loss of Neurons in the Basal Forebrain
Whitehouse, P., Price, D., Struble, R., Clark, A., Coyle, J., & DeLong, M. R. (1982) · Science · doi:10.1126/science.7058341 · Cited by 3,627
SELECTIVE LOSS OF CENTRAL CHOLINERGIC NEURONS IN ALZHEIMER'S DISEASE
DAVIES, P. (1976) · The Lancet · doi:10.1016/s0140-6736(76)91936-x · Cited by 3,565
Psychopharmacology: The third generation of progress
O’Connell, R. A. (1988) · Comprehensive Psychiatry · doi:10.1016/0010-440x(88)90057-0 · Cited by 3,020
Alzheimer disease: Evidence for selective loss of cholinergic neurons in the nucleus basalis
Whitehouse, P. J., Price, D. L., Clark, A. W., Coyle, J. T., & DeLong, M. R. (1981) · Annals of Neurology · doi:10.1002/ana.410100203 · Cited by 1,736
A 24-week, double-blind, placebo-controlled trial of donepezil in patients with Alzheimer's disease
Rogers, S. L., Farlow, M. R., Doody, R. S., Mohs, R., Friedhoff, L. T., & Donepezil Study Group* (1998) · Neurology · doi:10.1212/wnl.50.1.136 · Cited by 1,618
Human Memory and the Cholinergic System
Drachman, D. A. (1974) · Archives of Neurology · doi:10.1001/archneur.1974.00490320001001 · Cited by 1,398
NEUROTRANSMITTER-RELATED ENZYMES AND INDICES OF HYPOXIA IN SENILE DEMENTIA AND OTHER ABIOTROPHIES
Bowen, D. M., Smith, C. B., White, P., & DAVISON, A. N. (1976) · Brain · doi:10.1093/brain/99.3.459 · Cited by 1,313
APRIORITY
Asher, R. (1961) · The Lancet · doi:10.1016/s0140-6736(61)91217-x · Cited by 1,293

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Research works printed but not linked: 19

Sarter M., 1991, Cholinergic controversies, Trends Neurosci., 14, 483
Tariot, 1996, Contemporary treatment approaches to Alzheimer's disease, Consult. Pharm., 11, 16
Bartus, 1995, Aging in the Rhesus monkey: Debilitating effects on short term memory, J. NIH Res., 7, 69
Sathananthan, 1975, Cerebral vasodilators: A review, 155
Gallagher, 1998, Effects of aging on cognition and hippocampal/cortical systems, Soc Neurosci. Abstr., 24
Bartus, 1986, Commentary on animal models of Alzheimer's and Parkinson's disease, Integr. Psychiatry, 4, 74
Bartus, R., C. Flicker, and R. Dean. 1983. Logical principles in the development of animal models of age-related memory loss. In Clinical and Preclinical Assessment in Geriatric Psychopharmacology (T. Crook, Ed.), pp. 263–299. Mark Powley Associates, New Caanan, CT.
Bartus, 1983, Behavioral and pharmacological studies using animal models of aging: Implications for studying and treating dementia of Alzheimer's type, Banbury Rep., 1515, 207
Bartus, R. 1979. The effects of aging on visual memory, sensory processing and discrimination learning in a nonhuman primate. In Aging: Sensory Systems and Communication in the Elderly (J. Ordy, Ed.), pp. 85–113. Raven Press, New York.
Moss, 1986, Effects of Aging on visual recognition memory in the Rhesus monkey, Primate Rep., 14, 133
Bartus, 1979, Recent memory in aged nonhuman primates: Hypersensensitivity to visual interference during retention, Exp. Aging, 5, 385, 10.1080/03610737908257214 · DOI
Bartus, R., T. Crook, and R. Dean. 1987. Current progress in treating age-related memory problems: A perspective from animal preclinical and human clinical research. In Geriatric Clinical Pharmacology (G. Wood and R. Strong, Eds.), pp. 71–94. Raven Press, New York.
Bartus, R., and R. Dean. 1988. Effects of cholinergic and adrenergic enhancing drugs on memory in aged monkeys. In Current Research in Alzheimer Therapy (E. Giacobini and R. Becker, Eds.), pp. 179–190. Taylor and Francis, New York.
McEntee, 1991, Treatment of adult-onset cognitive disorders: results of multicenter trials, Psychopharmacol. Bull., 27, 41
Dean, 1982, Drug induced memory impairments in nonhuman primates, Soc. Neurosci. Abstr., 8, 322
Ogura, 1993, MK-801 impairs recogition memory in rhesus mondeys: comparison with cholinergic drugs, Pharmacol. Exp. Ther., 266, 60
Herz, 1960, Die Gedentung der Gahung fur die wirkung von scopolamin und ahnlichen, Z. Biol., 112, 104
Crowley, 1999, Big study hopes to find if Alzheimer's can be prevented in memory-impaired, Wall Street Journal.
Pang, 1998, Alzheimer's Disease, AAPS News, 1, 11

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Jiang, S., Li, Y., Zhang, C., Zhao, Y., Bu, G., Xu, H., & Zhang, Y. (2014) · Neuroscience Bulletin · doi:10.1007/s12264-013-1406-z · Cited by 147
Target Identification for CNS Diseases by Transcriptional Profiling
Altar, C. A., Vawter, M. P., & Ginsberg, S. D. (2008) · Neuropsychopharmacology · doi:10.1038/npp.2008.172 · Cited by 139
Cholinergic modulation of amyloid precursor protein processing with emphasis on M1 muscarinic receptor: perspectives and challenges in treatment of Alzheimer’s disease
Fisher, A. (2011) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2011.07507.x · Cited by 140
Triazole derivatives as inhibitors of Alzheimer's disease: Current developments and structure-activity relationships
Xu, M., Peng, Y., Zhu, L., Wang, S., Ji, J., & Rakesh, K. P. (2019) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2019.07.059 · Cited by 141
Further evidence for the cholinergic hypothesis of aging and dementia from the canine model of aging
Araujo, J. A., Studzinski, C. M., & Milgram, N. W. (2005) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2004.12.008 · Cited by 140
Nobiletin, a Citrus Flavonoid That Improves Memory Impairment, Rescues Bulbectomy-Induced Cholinergic Neurodegeneration in Mice
Nakajima, A., Yamakuni, T., Haraguchi, M., Omae, N., Song, S.-Y., Kato, C., Nakagawasai, O., Tadano, T., Yokosuka, A., Mimaki, Y., et al. (2007) · Journal of Pharmacological Sciences · doi:10.1254/jphs.sc0070155 · Cited by 137
Targeted delivery of nerve growth factor to the cholinergic basal forebrain of Alzheimer’s disease patients: application of a second-generation encapsulated cell biodelivery device
Eyjolfsdottir, H., Eriksdotter, M., Linderoth, B., Lind, G., Juliusson, B., Kusk, P., Almkvist, O., Andreasen, N., Blennow, K., Ferreira, D., et al. (2016) · Alzheimer s Research & Therapy · doi:10.1186/s13195-016-0195-9 · Cited by 137
Propidium-Based Polyamine Ligands as Potent Inhibitors of Acetylcholinesterase and Acetylcholinesterase-Induced Amyloid-β Aggregation
Bolognesi, M. L., Andrisano, V., Bartolini, M., Banzi, R., & Melchiorre, C. (2004) · Journal of Medicinal Chemistry · doi:10.1021/jm049156q · Cited by 136
Nerve growth factor metabolic dysfunction in Alzheimer's disease and Down syndrome
Iulita, M. F., & Cuello, A. C. (2014) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2014.04.010 · Cited by 141
Cholinergic dysfunction, neuronal damage and axonal loss in TgCRND8 mice
Bellucci, A., Luccarini, I., Scali, C., Prosperi, C., Giovannini, M. G., Pepeu, G., & Casamenti, F. (2006) · Neurobiology of Disease · doi:10.1016/j.nbd.2006.03.012 · Cited by 131
Symptomatic effect of donepezil, rivastigmine, galantamine and memantine on cognitive deficits in the APP23 model
Dam, D. V., Abramowski, D., Staufenbiel, M., & Deyn, P. P. D. (2005) · Psychopharmacology · doi:10.1007/s00213-004-2132-z · Cited by 132
Lecozotan (SRA-333): A Selective Serotonin 1A Receptor Antagonist That Enhances the Stimulated Release of Glutamate and Acetylcholine in the Hippocampus and Possesses Cognitive-Enhancing Properties
Schechter, L. E., Smith, D. L., Rosenzweig-Lipson, S. J., Rizzo, S. J. S., Dawson, L. A., Marquis, K. L., Jones, D., Piesla, M. J., Andree, T. H., Nawoschik, S. P., et al. (2005) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.105.086363 · Cited by 132
Gonadal Steroids, Learning, and Memory
Dohanich, G. P. (2002) · Elsevier eBooks · doi:10.1016/b978-012532104-4/50024-x · Cited by 130
Cholinergic Activity Enhances Hippocampal Long-Term Potentiation in CA1 during Walking in Rats
Leung, L.-W. S., Bixia Shen, A., Rajakumar, N., & Ma, J. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-28-09297.2003 · Cited by 130
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Alkondon, M., Pereira, E. F. R., Yü, P., Arruda, E. Z., Almeida, L. E. F., Guidetti, P., Fawcett, W. P., Sapko, M. T., Randall, W. R., Schwarcz, R. M., et al. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.5631-03.2004 · Cited by 129
The apolipoprotein E gene, attention, and brain function.
Parasuraman, R., Greenwood, P. M., & Sunderland, T. (2002) · Neuropsychology · doi:10.1037//0894-4105.16.2.254 · Cited by 134
and Alzheimer's disease
Brioni, J. D., Esbenshade, T. A., Garrison, T. R., Bitner, S. R., & Cowart, M. (2010) · Cited by 125
Alzheimer’s disease due to loss of function: A new synthesis of the available data
Kepp, K. P. (2016) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2016.06.004 · Cited by 123
Molecular mechanisms of brain-derived neurotrophic factor in neuro-protection: Recent developments
Zhao, H., Alam, A., San, C.-Y., Eguchi, S., Chen, Q., Lian, Q., & Ma, D. (2017) · Brain Research · doi:10.1016/j.brainres.2017.03.029 · Cited by 122
Challenging the cholinergic system in mild cognitive impairment: a pharmacological fMRI study
Goekoop, R., Rombouts, S. A. R. B., Jonker, C., Hibbel, A., Knol, D. L., Truyen, L., Barkhof, F., & Scheltens, P. (2004) · NeuroImage · doi:10.1016/j.neuroimage.2004.08.006 · Cited by 122
Cholinergic system function and cognition in mild cognitive impairment
Haense, C., Kalbe, E., Herholz, K., Hohmann, C., Neumaier, B., Krais, R., & Heiss, W. (2010) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2010.08.015 · Cited by 127
Combined Blockade of Cholinergic Receptors Shifts the Brain from Stimulus Encoding to Memory Consolidation
Rasch, B. H., Born, J., & Gais, S. (2006) · Journal of Cognitive Neuroscience · doi:10.1162/jocn.2006.18.5.793 · Cited by 137
Muscarinic Receptor Activation Protects Cells from Apoptotic Effects of DNA Damage, Oxidative Stress, and Mitochondrial Inhibition
Sarno, P. D., Shestopal, S. A., King, T. D., Zmijewska, A. A., Song, L., & Jope, R. S. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m212157200 · Cited by 121
Light-Induced Pupillary Responses in Alzheimer's Disease
Chougule, P. S., Najjar, R. P., Finkelstein, M. T., Kandiah, N., & Miléa, D. (2019) · Frontiers in Neurology · doi:10.3389/fneur.2019.00360 · Cited by 122
Cholinergic challenge in Alzheimer patients and mild cognitive impairment differentially affects hippocampal activation—a pharmacological fMRI study
Goekoop, R., Scheltens, P., Barkhof, F., & Rombouts, S. A. R. B. (2005) · Brain · doi:10.1093/brain/awh671 · Cited by 117
Comparison of ginsenosides Rg1 and Rb1 for their effects on improving scopolamine‐induced learning and memory impairment in mice
Wang, Q., Sun, L., Jia, W. W.-G., Liu, X., Dang, H., Mai, W., Wang, N., Steinmetz, A. A., Yu-qin, W., & Xu, C. (2010) · Phytotherapy Research · doi:10.1002/ptr.3130 · Cited by 115
α7 Nicotinic Receptor Up-regulation in Cholinergic Basal Forebrain Neurons in Alzheimer Disease
Counts, S., He, B., Che, S., Ikonomović, M. D., DeKosky, S. T., Ginsberg, S. D., & Mufson, E. J. (2007) · Archives of Neurology · doi:10.1001/archneur.64.12.1771 · Cited by 117

Authors: Bartus, R. T.
Affiliations: Alkermes (United States) (US)
Corresponding author: Bartus, Raymond T.
Venue: Experimental Neurology
Publisher: Elsevier BV
Published: 2000-06
Volume: 163
Issue: 2
Pages: 495-529
ISSN: 0014-4886 (ISSN-L)
DOI: 10.1006/exnr.2000.7397
OpenAlex: W2026745182
Cited by: 829
References: 231
Citations by year: 2026: 15 · 2025: 23 · 2024: 19 · 2023: 21 · 2022: 42 · 2021: 34 · 2020: 26 · 2019: 22 · 2018: 32 · 2017: 38 · 2016: 34 · 2015: 24 · 2014: 30 · 2013: 40 · 2012: 38
FWCI: 3.59
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Experimental Neurology (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Health Sciences › Medicine › Pharmacology (medical) › Cholinesterase and Neurodegenerative Diseases
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords: cholinergic hypothesis, Alzheimer's disease, neurodegenerative diseases, animal models of disease, Alzheimer's disease treatment, palliative care, cholinesterase inhibitors
MeSH terms: Age Factors, Alzheimer Disease, Animals, Cognition, Disease Models, Animal, Forecasting, Humans, Memory Disorders, Cholinergic Agents

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On Neurodegenerative Diseases, Models, and Treatment Strategies: Lessons Learned and Lessons Forgotten a Generation Following the Cholinergic Hypothesis

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