Cholinergic involvement in neurodegenerative diseases / edited by A. Claudio Cuello.

Format:

Book

Contributor:

Cuello, A. Claudio, editor.

Series:

Handbook of clinical neurology ; Volume 211.

Handbook of Clinical Neurology Series ; Volume 211

Language:

English

Subjects (All):

Cholinergic mechanisms.

Nervous system--Diseases.

Nervous system.

Physical Description:

1 online resource (575 pages)

Edition:

First edition.

Place of Publication:

San Diego, CA : Academic Press, [2025]

Summary:

Cholinergic Involvement in Neurodegenerative Diseases, Volume 211 reviews cholinergic function in the brain as it relates to Neurodegenerative disorders.Coverage includes Alzheimer's, dementia, Down Syndrome, Parkinson's, Huntington's, ALS, and more.

Contents:

Intro

Cholinergic Involvement in Neurodegenerative Diseases

Copyright

Handbook of Clinical Neurology 3rd Series

Foreword

Preface

Contributors

Contents

Chapter 1: A brief history of the CNS cholinergic transmission

Introduction

The Discovery of Acetylcholine as a Natural Substance

Cholinesterase Inhibition and Bioassays Support the Concept of Cholinergic Neurotransmission

The New Concept of Chemical Transmission of Nerve Impulses

Acetylcholine Function in the CNS

The Historical Significance of Cholinesterases

The Chemical vs Electrical Transmission Controversy

Chemical Neurotransmission at the Neuromuscular Junction

Synaptic Vesicles and Synaptosomes: The Debate

Quantal Release of Acetylcholine

The Identification of ``Cholinergic´´ Neurons in the CNS

Characterization and Classification of Cholinergic Neurons in the CNS

References

Chapter 2: Organization of the basal forebrain cholinergic system in the human brain

Cholinergic Systems in the CNS

Basal Forebrain Cholinergic Neurons and their Projections

Inputs Into the Basal Forebrain Cholinergic Cell Groups

Neurochemical Signatures of Basal Forebrain Cholinergic Neurons

Cortical Cholinergic Axons

Cortical Cholinergic Receptors and Acetylcholinesterase-Rich Cholinoceptive Neurons

Functional Affiliations

Acknowledgments

Chapter 3: The cholinergic synapses

Composition and Basic Elements of the Cholinergic Synapse

Cholinergic Synapses in Different Parts of the Nervous System

Central nervous system transmission

Different cholinergic receptors

Cholinergic function in CNS diseases

Alzheimer disease

Parkinson disease

Organophosphate poisoning

Inflammation

Cholinergic Synapses and Inflammation

The Cholinergic Implications of Ischemic Stroke.

Schizophrenia and bipolar disorder

Epilepsy

Cholinergic crisis

Pharmacology of the cholinergic synapse

Noncoding transcript aspects of the cholinergic network

Transfer RNA fragments targeting cholinergic transcripts

Chapter 4: Nicotinic acetylcholine receptors in the brain

Homomeric α7 nAChRs

Heteromeric nAChRs and their Functional Correlates

α4β2 nAChRs

Heteromeric α7β2 nAChRs

α3 Subunit-containing nAChRs

α5 Subunit-containing nAChRs

α6 Subunit-containing nAChRs

α8 Subunit-containing nAChRs

α9/α10 Subunit-containing nAChRs

Insights Into nAChR Structure: Biomedical and Pharmacologic Implications

Chapter 5: Cognition and modulation of the cholinergic system

Cognition and the Cholinergic System

Cholinergic Model of Alzheimer Disease

Cognitive Correlates of Increased Cholinergic Tone

Cognitive Correlates of Decreased Cholinergic Tone: The Scopolamine Model of Dementia

Microdosing of Scopolamine as a Cognitive Stress Test for Preclinical AD

Chapter 6: The involvement of the cholinergic system in Alzheimer disease

Memory and Basal Forebrain Cholinergic Neurons

A Cholinergic Hypothesis is Born

The Nascence and Evolution of Alzheimer's Cholinergic Therapy

Galantamine

Is There a Therapeutic Potential for Cholinergic Receptor Activation in Alzheimer Disease?

Nicotinic Receptors Agonists as Therapeutic Agents

Muscarinic Receptor Agonists as AD Therapeutic Agents

Closing Reflections About Cholinergic Transmission, Brain Remodeling, and Alzheimer's Therapy

Chapter 7: Structural changes to the basal forebrain cholinergic system in the continuum of Alzheimer disease

Cytoarchitectonic and Connectomic Mapping of the Basal Forebrain.

Altered Structural Integrity of the Basal Forebrain Nuclei in Aging and AD

Altered Structural Integrity of the Ascending Basal Forebrain Projections in Aging and AD

Accumulation of AD-Related Pathologies in the Basal Forebrain: A Cycle of Degeneration

Revisiting the Cortical Transsynaptic Spread Models of AD Progression

Conclusion and Future Research Directions

Chapter 8: The dependence of basal forebrain cholinergic neurons on NGF: The case in Alzheimer pathology

The Basal Forebrain Cholinergic System and Its Trophic Dependency

Discovery of NGF, Neurotrophins, and Their Receptors

The Neurotrophin Family

The Structure of NGF

Discovery of p75NTR

Discovery of TrkA

Distribution of the NGF Receptors Throughout the CNS

Interaction Between the TrkA and p75NTR Receptors

NGF Receptor Signal Transduction

Signal Transduction via TrkA

Ras/Raf/MEK/ERK

PLC-γ

PI3-kinase/AKT

Additional pathways

Signaling via p75NTR

p75NTR homodimers

p75NTR-TrkA heterodimers

p75NTR-sortilin heterodimers

Neurotrophin Receptor Vesicular Transport

Retrograde transport

Anterograde transport

The Concept of NGF-Dependent Survival of Basal Forebrain Neurons

Experimental Evidence for an NGF-Reparative Function of Basal Forebrain Cholinergic Neurons

NGF in AD and the Discovery of a Novel NGF Metabolic Pathway

Concluding Remarks

Chapter 9: NGF-based cholinergic therapies in Alzheimer disease

Background

Cholinergic pathways in physiology

ACh receptor-mediated signaling and the role of nerve growth factor (NGF)

Alzheimer disease and NGF pathways

Present status of AD therapy

NGF-based cholinergic therapies

Delivery of NGF to the brain

Intracerebroventricular and intracerebral delivery

Intranasal and intraocular delivery.

Viral vector-based gene delivery

Small molecule modulators

Encapsulated cell biodelivery

Conclusion

Chapter 10: Memory network and cognitive reserve are associated with preserved and stimulated cholinergic neurotransmission

The Cholinergic Impairment in Neurodegenerative Diseases

Alzheimer disease spectrum

Lewy body disease spectrum

Imaging Biomarkers of the Cholinergic System

Molecular neuroimaging

Cholinergic imaging

Imaging VAChT

Imaging nAChR

Imaging AChE

FDG-PET

Structural neuroimaging

The Cholinergic Modulation of Memory and Attention Networks

The cholinergic hypothesis of dementia and its revision

Cognitive Reserve and Cholinergic Neurotransmission

The concept of reserve

Neural mechanism underlying cognitive reserve

The concept of compensation

The cognitive reserve and the cholinergic system

Evidence in AD

Evidence in LBD

Chapter 11: Cholinergic therapy in Alzheimer disease

Steps Leading to Regulatory Approval of ChEIs for AD

Steps Leading to Clinical Use of ChEIs

Clinical Benefit of ChEIs for Non-AD Dementias

Limitations of Cholinergic Therapies for AD

Efforts at Enhancing the Clinical Efficacy of ChEIs

Lessons Learned From Optimal Testing and Use of New Drugs for AD

Chapter 12: CNS muscarinic receptors and muscarinic receptor agonists in Alzheimer disease treatment

Introduction11Abbreviations used in the chapter are listed at the end of the chapter before References section.

Muscarinic Acetylcholine Receptor Subtypes in the Brain

Muscarinic Acetylcholine Receptor Subtypes in Peripheral Tissues

Muscarinic Acetylcholine Receptor Subtype Expression in the Human Brain and AD

M1 mAChR Is a Potential Therapeutic Target in AD.

M1 Agonists for Symptomatic Treatment and as Disease-Modifying (DM) Agents in AD

Concluding Remarks and Outlook

Competing interests

Chapter 13: The cholinotrophic system in Down syndrome

Gestation of Primate Basal Forebrain Neurons

Chemoanatomy of the CBF in the Neurotypical Brain

Prenatal Development of the CBF System in DS

Postnatal ChAT in the CBF in DS

Abnormalities in CBF Target Sites in DS

Cholinergic Muscarinic and Nicotinic Receptors in DS

NGF Pathobiology in DS

Trk Receptors in the CBF of DS

p75NTR Receptors in the CBF of individuals with DS

NGF Metabolic Pathways in DS

Amyloid and the CBF Connectome in DS

Intracellular Amyloid in CBF Connectome in DS

Tau Pathology in the CBF system in DS

Tau Pathology in Cholinergic Striatal Neurons in DS

Amyloid Pathology and the Cholinergic Striatum in DS

Spliceosome Dysfunction in Cortical Cholinergic Projection Sites in DS

Gene Expression Within the CBF Connectome in DS

Cholinotrophic Biomarkers for DS

Cholinotrophic Treatment Strategies for DS

NGF Treatment for DS

Small Molecule Neurotrophins to Treat CBF Degeneration in DS

Concluding Comments

Future Directions

Conflict of interest

Chapter 14: The involvement of the cholinergic system in Parkinson disease

Terminology

Clinical approaches to investigate cholinergic dysfunction

Clinical Correlates of Cholinergic Dysfunction in PD

Motor Manifestations

Cardinal motor symptoms and dyskinesia

Gait problems and falls

Freezing of gait

Non-motor Manifestations

Cognitive decline

Pathologic studies

Neuroimaging studies

Neurophysiologic studies

Neuropsychiatric symptoms

Depression

Visual hallucinations

Sleep problems

Olfactory dysfunction.

Autonomic dysfunction.

Notes:

Includes bibliographical references and index.

Description based on publisher supplied metadata and other sources.

Description based on print version record.

ISBN:

0-443-15550-X

0-443-19088-7

OCLC:

1519994545