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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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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