The Neuroscience of Dementia

Description

The Neuroscience of Dementia brings together different fields of dementia research into a single book, covering a wide 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, molecular biology, and more. This foundational, comprehensive book compiles the latest understanding on all forms of dementia and their common features in a single source. It is an invaluable resource for neuroscientists, neurologists, and anyone in the field. Front Cover GENETICS, NEUROLOGY, BEHAVIOR, AND DIET IN DEMENTIA GENETICS, NEUROLOGY, BEHAVIOR, AND DIET IN DEMENTIA Copyright Contents Contributors Foreword Preface I - Genetics, molecular and cellular biology 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 neurodevelopmental-related phenotypes Neuron navigator 2 variants are associated with carotid plaque, which is a pathophysiologic change for Alzheimer's disease Knockdown neuron navigator 2 gene results in a reduction in all-trans retinoic acid–mediated neurite outgrowth, which is a ... Differentially expressed neuron navigator 2 was identified in the hippocampal brain region from patients with Alzheimer’s d ... 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 family study followed by a con ... 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 (PICALM) gene 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 Alzheimer's disease EEG and PICALM genotype Event-related potentials, P300 and PICALM Conclusion Key facts of the role of PICALM genotype in metabolic dysregulation and neurophysiological alterations during ageing 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 genetic causes of disease 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 genes 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 polymorphisms 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 modifications 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 disease neurodegene ... 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 disease 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 disease 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-site amyloid precursor ... Evidence for a role of beta-site amyloid precursor protein cleaving enzyme 1 and A disintegrin and metalloproteinase 10 gen ... 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 C 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, amyotrophic lat ... 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: insights from anim ... 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 cognitively compromised elderly 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 31 - Limitations of amyloid imaging in Alzheimer's disease List of abbreviations Mini-dictionary of terms Introduction Amyloid imaging for diagnosis of early or mild dementia Amyloid imaging for diagnosis and prognosis of mild cognitive impairment Impact of amyloid imaging on patient management Radiologic diagnosis for mild cognitive impairment or early dementia Subjective cognitive decline Therapeutic trials: patient selection and tracking disease progression Key facts of amyloid imaging Summary points References 32 - Linking gradient echo plural contrast imaging metrics of tissue microstructure with Alzheimer disease List of abbreviations Mini-dictionary of terms Gradient echo plural contrast imaging—biophysical and biological background GEPCI R2t∗ measurements are sensitive to neuronal damage and correlate with cognition and disease progression GEPCI R2∗ metric provides a surrogate measure of Aβ accumulation in the brain Brain patterns of GEPCI R2∗ and R2t∗ metrics allow distinguishing among healthy control, preclinical, and mild AD groups Conclusions Summary points Key facts (areas of interest) Funding References 33 - Hypertensive disorders during pregnancy and later dementia: is there a connection? List of abbreviations Mini-dictionary of terms Introduction Hypertensive disorders during pregnancy Classification Risk factors for preeclampsia Pathophysiology of preeclampsia Cardiovascular disease after hypertensive disease during pregnancy Genetic and epigenetic similarities between Alzheimer's disease and preeclampsia Cerebral blood flow during preeclampsia Posterior reversible encephalopathy syndrome Stroke and preeclampsia/eclampsia Other signs of neurological damage in preeclampsia/eclampsia Cognitive functioning and previous preeclampsia/eclampsia Cerebral white-matter lesions Hypertensive disorders of pregnancy and dementia Key facts about preeclampsia Summary points References 34 - Unraveling the contributions of sleep dysfunction to Alzheimer's disease List of abbreviations Mini-dictionary of terms Introduction Pathological protein species and sleep Sleep dysfunction and Alzheimer's dementia Perspectives Key facts about the regulation of sleep and wake Summary points References III - Behaviour and psychopathology 35 - Overview of behaviors in dementia List of abbreviations Introduction Challenging behaviors Cognitive changes Agitation and aggression Categories of agitation Sundowning syndrome/wandering Sleep impairment Inappropriate sexual behavior Hoarding Psychiatric symptoms associated with dementia Psychosis Delusions/illusions Depression Conclusion Key facts for behavioral disturbances Summary points References 36 - Delirium superimposed on dementia: a clinical challenge from diagnosis to treatment Mini-dictionary of terms Introduction The epidemiology of delirium in the context of dementia The under recognition of delirium in the context of dementia The diagnosis of delirium in the context of dementia Prevention and treatment of delirium in dementia Key facts of delirium Summary points References 37 - Self-consciousness deficits in dementia List of abbreviations Mini-dictionary of terms Introduction Self-consciousness Self-consciousness in neurodegenerative diseases Enhancing elements of self-consciousness in neurodegenerative diseases Key of facts of self-consciousness Summary points References 38 - Attentional impairments to novel images in dementia List of abbreviations Mini-dictionary of terms Measuring attentional impairments toward novel images in dementia Correlates of attentional impairments in dementia and prodromal stages Putative mechanisms underlying attentional impairments in dementia Pharmacological treatment of attentional impairments in dementia Key facts of the visual-paired comparison task Summary points References 39 - Frontal lobe syndrome and dementias List of abbreviation Mini-dictionary of terms Introduction Neuroanatomy of the main frontal lobe circuits Frontal lobe syndromes Neuropsychological assessment Frontal lobe syndrome in neurodegenerative diseases Alzheimer disease Frontotemporal dementia Dementia with lewy bodies Parkinson's disease Epidemiology Conclusion Key facts of frontal lobe syndrome Summary points References 40 - The stigma of dementia List of abbreviations Mini-dictionary of terms Introduction Stigma: theory and development The development of stigma Repercussions of stigma Future developments Key facts of the national Alzheimer's Project Act Summary points References 41 - Delusions in dementias List of abbreviations Mini-dictionary of terms Introduction Epidemiology Several types of delusions for several types of dementia Risk factors Neuroanatomy and neuroimaging Neurobiology Delusions and cognition Conclusions Key facts of organic psychosis Summary points References 42 - Linking motor speech function and dementia List of abbreviations Mini-dictionary of terms Introduction Aims of this review Motor speech as a component of verbal expression Dysarthria and apraxia of speech Alzheimer's disease Amnestic presentation Language presentation (logopenic variant primary progressive aphasia) Visuospatial presentation (posterior cortical atrophy) Frontotemporal dementia Behavioral variant frontotemporal dementia Semantic variant primary progressive aphasia Nonfluent/agrammatic variant of primary progressive aphasia Progressive apraxia of speech Dementia with lewy bodies Conclusion Key facts about dysarthria Summary points References 43 - Spatial navigation and Alzheimer's disease List of abbreviations Mini-dictionary of terms Introduction Neural representations and spatial navigation Spatial navigation circuitry and structural change in Alzheimer's disease Measuring spatial navigation in human subjects Spatial frames of reference and navigation in Alzheimer's disease Assessment of spatial navigation in rodent models of Alzheimer's disease Neural representations of space in rodent models of Alzheimer's disease Summary and conclusions Key facts Summary points Acknowledgments References 44 - Violence and dementia List of abbreviations Mini-dictionary of terms Introduction Defining violence Violence and neurobiology Dementia and violence What factors are associated with violence? Violent behavior in different types of dementia Violence and psychotic symptomatology Management Nonpharmacologic interventions Pharmacologic interventions Key facts of violence and dementia Summary points References 45 - Factors contributing to protection and vulnerability in dementia caregivers List of abbreviations Mini-dictionary of terms Introduction Stressors in dementia caregiving The influence of cultural values Caregiver protective factors Concluding remarks and future research Key facts of dementia caregiving Summary points References IV - Diet, nutrition and environment 46 - Nutritional status of dementia and management using dietary taurine supplementation List of abbreviations Mini-dictionary of terms Introduction Nutritional problems of dementia Nutritional management of dementia Antioxidant vitamins Dietary fatty acids Taurine Conclusion Summary points Key facts about taurine References 47 - Selenium and Alzheimer's disease Mini-dictionary of terms Introduction Selenium metabolism Selenium and the brain Experimental studies Human studies Conclusions Key facts of selenium Summary points References 48 - Linking adiponectin and obesity in dementia List of abbreviations Mini-dictionary of terms Introduction Obesity as risk factor of dementia Adipose tissue as an endocrine organ Adiponectin Adiponectin in the brain – experimental studies Adiponectin and dementia – clinical studies Adiponectin and dementia biomarkers Adiponectin – therapeutic perspectives Key facts on obesity Summary points References 49 - The impact of the gut microbiome in Alzheimer's disease: cause or consequence? Mini-dictionary of terms Introduction Microbial changes in Alzheimer's disease Eating and digestion habits in Alzheimer's disease Impact of symptomatic treatments on the gut microbiome Pro- and antipathological properties of bacterial endogenous metabolites Therapeutic and diagnostic options Key facts of the gut and its microbiome Summary points References 50 - (-)-Epigallocatechin-3-gallate and Alzheimer's disease List of abbreviations Mini-dictionary of terms Therapeutic potential of (-)-epigallocatechin-3-gallate in the secondary prevention of cognitive decline and Alzheimer's di ... Green tea and (-)-epigallocatechin-3-gallate antineurodegenerative effects: epidemiological and clinical evidence Mechanisms behind the effect: evidence from animal models Reduction of oxidative stress Modulation of neuroinflammation Modification of amyloid precursor protein metabolism and tau phosphorylation Specific effects on plasticity and neurogenesis (-)-Epigallocatechin-3-gallate as a possible treatment for Alzheimer's disease? Future perspectives Key facts of (-)-epigallocatechin-3-gallate Summary points References 51 - Lead, cadmium and Alzheimer’s disease List of abbreviations Mini-dictionary of terms Introduction Lead and Alzheimer’s disease Prevalence Overall lead health effects General mechanisms linking lead exposure to AD Exposure sources: ingestion, inhalation, endogenous Absorption into the bloodstream and travel to the brain General consequences in the brain Experimental studies linking lead exposure and AD Mouse model lead treatment: Aβ deposition, tau expression, altered learning Rat model lead treatment: Aβ deposition, tau expression, synaptic density, impaired learning Monkey model lead treatment: APP expression, Aβ deposition, tau levels Summary of lead exposure and human dementia epidemiology Cadmium and Alzheimer’s disease How can cadmium reach the brain? Experimental studies linking cadmium exposure and AD Oxidative stress, neuroinflammation, and apoptosis in neuronal cells by cadmium Increased Aβ production and tau tangles by cadmium Cadmium-induced cholinergic neuron toxicity Human studies of cadmium exposure and AD and cognition Postmortem cadmium comparison between AD brains and normal brains Epidemiologic studies of the association between cadmium exposure and AD Conclusion Key facts of lead and cadmium Summary points References V - Models and modelling in dementia 52 - Alzheimer model 5xfad mice and applications to dementia: transgenic mouse models, a focus on neuroinflammation ... List of abbreviations Mini-dictionary of terms Introduction Development of transgenic mouse models for AD Neuroinflammation and microglial functions as therapeutic targets for AD Evaluating the preventive effects of food-derived components using 5xFAD mice Iso-α-acids, bitter components in beer, prevent the development of AD-like pathologies in 5xFAD mice Conclusion Key facts of dementia prevention Summary points References 53 - Use of 192 IgG-saporin as a model of dementia and its application List of abbreviations Basal cholinergic system 192 IgG-saporin–induced rat model of dementia Experimental application of 192 IgG-saporin–induced dementia Neurogenesis and the role of the cholinergic signal Therapeutic drug tests Deep brain stimulation for dementia Others References 54 - Amyloid beta 1–42-induced animal model of dementia: a review List of abbreviations Mini-dictionary of terms Introduction Alzheimer's disease pathogenic events Experimental models of Alzheimer's disease Dementia animal model induced by amyloid beta 1–42 Conclusion Key facts Summary points References 55 - Resources for the neuroscience of dementia . Introduction Summary points . Acknowledgments References Index A B C D E F G H I J K L M N O P Q R S T U V W X Back Cover