The Neuroscience of Dementia 1st Edition by Colin R Martin, Victor R Preedy ISBN 9780128160435 0128160438

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ISBN 10: 0128160438
ISBN 13: 9780128160435
Author: Colin R Martin, Victor R Preedy

Genetics, Neurology, Behavior, and Diet in Dementia: The Neuroscience of Dementia, Volume 2 consolidates different fields of dementia research into a single book, covering a range of subjects, including Alzheimer’s disease, Lewy body dementia, mixed dementia, vascular dementia, physical activity, risk factors, mortality, biomarkers, SPECT, CT, MRI, questionnaires, nutrition, sleep, delirium, hearing loss, agitation, aggression, delusions, anxiety, depression, hallucinations, psychosis, senile plaques, tau and amyloid-beta, neuroinflammation, and molecular biology. This foundational, comprehensive book assembles the latest understanding on all dementias and their common features in a single source. It is an invaluable resource for neuroscientists, neurologists, and anyone in the field.

• Offers comprehensive coverage of a broad range of topics related to dementia
• Serves as a foundational collection for neuroscientists and neurologists on the biology of dementia and brain dysfunction
• Contains in each chapter an abstract, key facts, mini dictionary of terms, and summary points to aid in understanding
• Provides unique sections on specific subareas, intellectual components, and knowledge-based niches that will help readers navigate key areas for research and further clinical recommendations
• Features preclinical and clinical studies to help researchers map out key areas for research and further clinical recommendations
• Serves as a “one-stop” source for everything you need to know about dementia

The Neuroscience of Dementia 1st Edition Table of contents:

1 – The neuron navigator 2 gene and Alzheimer’s disease

List of abbreviations

Introduction

Research findings of neuron navigator 2 based on animal studies

Research findings of neuron navigator 2 based on human studies

Neuron navigator 2 is associated with Alzheimer’s disease as well as age-related and neurodevelopmen

Neuron navigator 2 variants are associated with carotid plaque, which is a pathophysiologic change f

Knockdown neuron navigator 2 gene results in a reduction in all-trans retinoic acid–mediated neuri

Differentially expressed neuron navigator 2 was identified in the hippocampal brain region from pati

Neuron navigator 2 de novo mutations have been discovered in autism spectrum disorders

Neuron navigator 2 genetic variants showed strong associations with Alzheimer’s disease in a famil

Future outlook and conclusions

Key facts of neuron navigator 2 gene and Alzheimer’s disease

Summary points

Disclosure

References

2 – Interlinking polymorphisms, estrogens, and Alzheimer disease

List of abbreviations

Mini-dictionary of terms

Introduction

Estrogen, cognition, and AD

Estrogen receptors and their genetic polymorphisms in AD

ERα and ERβ

ESR1 in AD

ESR2 in AD

Conclusions

Key facts of the “critical window hypothesis”

Summary points

References

3 – Linking EEGs, Alzheimer disease, and the phosphatidylinositol-binding clathrin assembly protein

List of abbreviations

Mini-dictionary of terms

Introduction

Functions of PICALM and their potential influence on AD development

PICALM and AD risk

Role of PICALM in amyloidogenesis

Role of PICALM in Aβ clearance

Role of PICALM in tau clearance

PICALM and synaptic functions

PICALM and cholesterol metabolism

PICALM and iron homeostasis in AD

EEG – method for studying the effect of genetic influence on brain function in normal ageing and Alz

EEG and PICALM genotype

Event-related potentials, P300 and PICALM

Conclusion

Key facts of the role of PICALM genotype in metabolic dysregulation and neurophysiological alteratio

Summary points

References

4 – CD36 gene polymorphisms and Alzheimer’s disease

List of abbreviations

Mini-dictionary of terms

Introduction

Pathogenesis of Alzheimer’s disease

Amyloid hypothesis and CD36 receptors

CNS oxidative stress, inflammatory processes and CD36

Disturbances of cholesterol metabolism and CD36

Taste sensation and CD36 receptor

CD36 gene polymorphisms

Conclusions and future directions

Key facts of CD36 receptor in brain and Alzheimer disease

Summary points

Acknowledgments

References

5 – Genetic contributions to sporadic frontotemporal dementia

List of abbreviations

Mini-dictionary of terms

Heterogeneous clinical presentations and underlying neuropathology complicate the identification of

Clinical presentation defines syndromic diagnosis of frontotemporal dementia subtype

Defining familial and sporadic disease

Genetics of sporadic disease: involvement of established familial frontotemporal lobar degeneration

Genetics of sporadic disease: involvement of rare familial disease genes

Common variant risk factors: genome-wide association studies

Common variant risk factors: pleiotropy

Summary

Key facts of frontotemporal dementia

Summary points

References

6 – Clinical response to cholinesterase inhibitors in dementia: the role of CYP2D6 and APOE genetic

List of abbreviations

Mini-dictionary of terms

Dementia: concepts and risk factors

APOE

Pharmacological treatment

The concept of good, neutral, and bad clinical responders

Medication response

Predictive factors of response

CYP2D6 phenotype and genetic variants

CYP2D6 genetic variants as Alzheimer disease risk factor

CYP2D6 and Alzheimer disease treatment response

Key facts of metabolized drugs

Summary points

References

7 – A1 and A2 purinergic receptor expression in dementia

List of abbreviations

Mini-dictionary of terms

Introduction

Purinergic receptors

A1 and A2 purinergic receptors in neuropathologies

A1R in Alzheimer’s disease

Key facts of P1 purinergic receptors

Summary points

References

8 – Molecular aspects of metallothioneins in dementias

List of abbreviations

Mini-dictionary of terms

Key facts of neuroinflammation

Key facts of metallothioneins

Summary points

Acknowledgments

References

9 – Implication of microRNAs in Alzheimer’s disease pathogenesis

List of abbreviations

Mini-dictionary of terms

Introduction

Genetics, epigenetics, and pathology of Alzheimer’s disease

MicroRNAs regulating amyloid precursor protein expression and processing

MicroRNAs regulating microtubule-associated protein tau expression and its posttranslational modific

MicroRNAs regulating synaptic functions, endocytosis, and phagocytosis

Key facts of microRNAs

Summary points

Acknowledgments

References

10 – Role of cellular oxidative stress in dementia

List of abbreviations

Mini-dictionary of terms

Introduction

Oxidative stress in Alzheimer’s disease

Oxidative stress in Parkinson’s disease

Oxidative stress in Huntington’s disease

Oxidative stress in spongiform encephalopathies

Oxidative stress in other types of dementia

Key facts of oxidative stress

Summary points

References

11 – Toward an integrative understanding of the neuroinflammatory molecular milieu in Alzheimer dise

List of abbreviations

Mini-dictionary of terms

Alzheimer disease overview

Alzheimer disease etiology

Alzheimer disease pathophysiology and the amyloid hypothesis

The inflammatory milieu: the core of Aβ pathology in Alzheimer disease?

Inflammatory response in the central nervous system

TLR-mediated neuroinflammatory response in Aβ pathology

Ageing and the proinflammatory scenario

Ageing and the proinflammatory scenario: additional clues from menopause

Concluding remarks

Key facts on neurodegeneration

Summary points

Acknowledgments

References

12 – Wnt signaling and dementia

List of abbreviations

Mini-dictionary of terms

Introduction

Canonical Wnt pathways

Noncanonical Wnt pathways

The role of Wnt in the central nervous system

The role of Wnt signaling in dementia

Wnt signaling and Alzheimer’s disease

Wnt signaling and frontotemporal dementia

The role of Wnt signaling in vascular dementia

Targeting the Wnt signaling pathways

Key facts of dementia

Summary points

Funding

References

13 – Linkage of atypical protein kinase C to Alzheimer disease

List of abbreviations

Introduction

Relationship of obesity, metabolic syndrome, and T2DM to AD

General aspects of insulin signaling

Insulin signaling in brains of humans afflicted by nondiabetic AD

Insulin signaling in brains of humans afflicted with AD associated with T2DM and pre-T2DM

Insulin signaling in brains of animal models of insulin-resistant forms of obesity and T2DM

Central role of the liver in insulin-resistant states of obesity and T2DM

Supporting evidence of Akt and aPKC activation in brains of AD humans and HFF mice

Supporting evidence that insulin increases Aβ1-40/42

Knockout of mouse PKC-λ diminishes insulin-simulated increases in Aβ1-40/42 and p-Tau

Tau phosphorylation in insulin-resistant states

Use of nasal insulin for AD treatment

Potential salutary effects of insulin in AD

Alterations in brain insulin signaling factors in transgenic AD models

aPKC inhibitors

In vivo effects of aPKC inhibitors on liver versus brain aPKC

In vitro effects of PKC-ι/λ activators and inhibitors

Selective inhibition of brain PKC-λ/ι by ICAP

ICAP and AICAR: similarities and differences

Potential mechanisms of β-secretase activation by aPKC

aPKC requirements for memory functions

Potential uses of inhibitors of brain PKC-ι/λ for AD treatment

Bullet points

References

14 – Linking histone deacetylases and phosphodiesterase 5 in novel treatments for Alzheimer’s diseas

List of abbreviations

Mini-dictionary of terms

The molecular basis of dementia

The role of histone deacetylase inhibition in Alzheimer’s disease

The role of phosphodiesterase 5 inhibition on Alzheimer’s disease

The effects of simultaneous histone deacetylase and phosphodiesterase 5 inhibition on Alzheimer’s di

Key facts

Key facts of Alzheimer’s disease

Key facts of combination therapies

Summary points

References

15 – Nuclear factor erythroid 2-related factor 2 in Alzheimer’s disease

List of abbreviations

Mini-dictionary of terms

Introduction

The role of nuclear factor erythroid 2-related factor 2 in redox balance

The role of nuclear factor erythroid 2-related factor 2 in mitochondrial maintenance

The role of nuclear factor erythroid 2-related factor 2 in antiinflammation

The role of nuclear factor erythroid 2-related factor 2 in autophagy

Conclusion

Key facts of nuclear factor erythroid 2-related factor 2

Summary points

References

16 – Implications of alpha- and beta-secretase expression and function in Alzheimer’s disease

List of abbreviations

Mini-dictionary of terms

Introduction

Balance of alpha- and beta-secretase in aging and Alzheimer’s disease

Mouse models with central nervous system manipulation of A disintegrin and metalloproteinase 10/beta

Evidence for a role of beta-site amyloid precursor protein cleaving enzyme 1 and A disintegrin and m

Secretase expression in mild cognitive impairment and Alzheimer’s disease

Secretase expression in normal aging

Key facts of proteases acting on the amyloid precursor protein

Summary points

References

17 – Methylation analysis of DNA in Alzheimer’s disease

List of abbreviations

Mini-dictionary of terms

Introduction

DNA methylation and hydroxymethylation

Early studies of DNA methylation in cell cultures and animal models of Alzheimer’s disease

Methylation studies in Alzheimer’s disease tissues

Conclusions

Key facts of DNA methylation in Alzheimer’s diseases

Summary points

References

18 – The signalosome malfunctions in age-associated neuropathologies

List of abbreviations

Mini-dictionary of terms

Introduction

The signalosome concept

Lipid raft anomalies and neuropathology

Lipid raft molecules as potential biomarkers of neurodegeneration

Essential fatty acids for healthy neurons

Supplementary PUFA to prevent cognitive decline?

Key facts of age-associated neuropathology

Key facts of neurolipidomics in brain pathology

Summary points

References

19 – FAM3C in Alzheimer’s disease: a risk-related molecule and potential therapeutic target

List of abbreviations

Mini-dictionary of terms

Introduction

Regulation of γ-secretase cleavage and identification of family with sequence similarity 3, member

FAM3C reduces amyloid-β production by destabilizing APP-C99

The FAM3 superfamily

FAM3A

FAM3B

FAM3C

FAM3D

Neuronal FAM3C expression

Reduction of brain FAM3C expression with aging and in patients with Alzheimer’s disease

Conclusion and perspective

Key facts of the molecular pathomechanism of Alzheimer’s disease

Summary points

Acknowledgments

References

20 – Amylin and amylin receptors in Alzheimer’s disease

List of abbreviations

Mini-dictionary of terms

Introduction

Amylin, a neuroendocrine hormone

Amylin receptors, multiplexed signaling, and regulation

Amylin in Alzheimer’s disease

Common features of human amylin and beta amyloid peptide, amyloid proteins

Amylin receptors involved in memory and learning

Amylin receptors, mediated neuronal cytotoxicity

Amylin and amylin receptor involved in beta amyloid peptide–related neuroinflammation reaction

Amylyin receptor involved in hippocampal long-term potentiation

Modulation of amylin receptors to improve cognitive function in Alzheimer’s disease

Conclusion

Key facts of Alzheimer’s disease and amylin

Summary points

References

21 – Mammalian target of rapamycin complexes: regulation and Alzheimer’s disease

List of abbreviations

Mini-dictionary of terms

Introduction

Mammalian target of rapamycin and regulation

Alzheimer’s disease

Conclusion

Key facts

Summary points

References

Further reading

22 – Mammalian target of rapamycin complexes: protein synthesis and autophagy, Parkinson’s disease,

List of abbreviations

Mini-dictionary of terms

Introduction

Mammalian target of rapamycin control of protein synthesis and autophagy

Parkinson’s disease

Amyotrophic lateral sclerosis and frontotemporal dementia

Mammalian target of rapamycin–based treatment

Conclusion

Key facts

Summary points

References

23 – Linking CD200 in brains and dementia: molecular aspects of neuroinflammation

List of abbreviations

Mini-dictionary of terms

Introduction

CD200’s role in the periphery

CD200 in experimental models of neurodegeneration: implications for Alzheimer’s disease

Factors increasing the expression of CD200 in the brain

Conclusions

Key facts on neuroinflammation

Summary points

References

II – Neurological, physiological and imaging

24 – Hippocampal atrophy associated with dementia risk factors and dementia

List of abbreviations

Mini-dictionary of terms

Introduction

Dementia risk factors and the hippocampus

Diabetes

Hypertension

Chronic kidney disease

Alcohol

Education

Depression

Hearing loss

Atrial fibrillation

Diet and obesity

Physical and cognitive activity

Alzheimer-type dementia and the hippocampus

Apolipoprotein E genotype

Preclinical phase of Alzheimer’s disease

Mild cognitive impairment

Vascular cognitive impairment and the hippocampus

Small-vessel disease

White-matter lesions

Poststroke hippocampal atrophy

Conclusions

Key facts of hippocampal atrophy

Summary points

References

25 – Inflammation and insulin resistance in Alzheimer’s disease: partners in crime

List of abbreviations

Mini-dictionary of terms

Introduction

Inflammation features in Alzheimer’s disease

Inflammation-targeted treatments in Alzheimer’s disease

Impairments in metabolism and insulin signaling in Alzheimer’s disease

Inflammation and its effects on insulin signaling

Insulin-based treatments in Alzheimer’s disease

Conclusions

Key facts

Summary points

Acknowledgments

References

26 – Brain susceptibility to hypoxia/hypoxemia and metabolic dysfunction in Alzheimer’s disease: ins

List of abbreviations

Mini-dictionary of terms

Introduction

The neurovascular unit

Blood–brain barrier in Alzheimer’s disease

Astrocytes in AD

Pericytes in AD

Impact of hypoxia/hypoxemia on neuronal function in AD

Hypoxia/hypoxemia and neurons

Hypoxia/hypoxemia and myelin-forming cells

Key facts of neurovascular unit

Summary points

References

27 – Neuropeptides and neurolipids: what they are and how they relate to Alzheimer’s disease

List of abbreviations

Mini-dictionary of terms

Introduction

Neuropeptides

Galanin

Opioid peptides

Substance P

Neuropeptide Y

Corticotropin-releasing factor

Somatostatin

Cholecystokinin

Neurolipids

Cannabinoids

Sphingosine-1-phosphate receptors in AD

Lysophosphatidic acid receptors in AD

Orphan receptors

Key facts of neuropeptides

Key facts of neurolipids

Key facts of neuropeptides and neurolipids in Alzheimer’s disease

Summary points

References

28 – Neurotransmitter receptors in Alzheimer’s disease: from glutamatergic to cholinergic receptors

List of abbreviations

Mini-dictionary of terms

Introduction

Glutamatergic and GABAergic receptors

Monoamine receptors

Noradrenergic receptors

Dopaminergic receptors

Serotonergic receptors

Cholinergic receptors

Nicotinic acetylcholine receptors in AD

Muscarinic acetylcholine receptors in AD

Key facts about glutamate in Alzheimer’s disease

Key facts about GABA receptors in Alzheimer’s disease

Key facts about monoaminergic receptors in Alzheimer’s disease

Key facts about the cholinergic system in Alzheimer’s disease

Summary points

References

29 – Aβ42-α7-like nicotinic acetylcholine receptors and Alzheimer’s disease

List of abbreviations

Mini-dictionary of terms

Introduction to toxicity of soluble Aβ

α7nAChR as the soluble Aβ target driving AD pathogenesis

Identification of the critical Aβ- and α7nAChR-binding domains for Aβ42-α7nAChR interaction

Aβ42-α7nAChR interaction in AD and normal aging in brain and lymphocytes

Reducing Aβ42’s binding to α7nAChR as a disease-modifying therapeutic approach in AD and cognitive

Key facts of amyloid-β in Alzheimer’s disease

Summary points

References

30 – Synaptosomal bioenergetic defects in Alzheimer’s disease

List of abbreviations

Mini-dictionary of terms

Introduction

Pathological hallmarks of Alzheimer’s disease

Alzheimer’s disease and brain bioenergetics

Synaptic mitochondrial bioenergetics

Involvement of “synaptopathy” in Alzheimer’s disease pathogenesis

Synaptosomal bioenergetic defects in Alzheimer’s disease transgenic rodent models

J20 mice

Tg2576

Amyloid precursor protein/presenilin 1

5xTg

McGill-R-Thy1-APP

Modulation of synaptosomal bioenergetics in hemizygous McGill-R-Thy1-APP rats

Key facts of brain bioenergetics and Alzheimer’s disease

Summary points

References

Index

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Tags: Colin R Martin, Victor R Preedy, Neuroscience, Dementia