| Contributors |
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xiii | |
| Preface |
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xvii | |
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1 Fluid biomarker-based molecular phenotyping of Alzheimer's disease patients in research and clinical settings |
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3 | (22) |
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4 | (1) |
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2 Molecular pathogenesis of Alzheimer's disease |
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5 | (1) |
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3 Biomarkers to dissect the pathological heterogeneity of Alzheimer's disease in vivo |
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6 | (1) |
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4 Pathophysiological basis for the core AD CSF biomarkers |
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7 | (2) |
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5 Diagnostic performance of the core AD CSF biomarkers |
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9 | (1) |
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6 Refining measurement through standardization and automated lab analyzers |
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10 | (1) |
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7 Synaptic biomarkers for AD |
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11 | (1) |
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8 Blood biomarkers for AD |
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11 | (4) |
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9 Application of fluid biomarkers in epidemiological and genetic studies |
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15 | (1) |
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16 | (1) |
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16 | (9) |
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2 Tracking down a missing trigger for Alzheimer's disease by mass spectrometric imaging based on brain network analysis |
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25 | (32) |
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1 A missing trigger for Alzheimer's disease (AD)? |
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26 | (1) |
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2 AD is a disease and not a final stage of physiological aging |
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27 | (5) |
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3 How do we select AD subjects for future research? |
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32 | (4) |
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4 We need to understand the hierarchical organization of brain functions related to AD |
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36 | (4) |
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5 The default mode network (DMN) might be a target for future research to find the initial trigger for AD |
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40 | (4) |
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6 Matrix-assisted laser desorption ionization (MALDI)-based imaging mass spectrometry (IMS) as tool for comparing systematically biomolecular changes in AD brains with those in age-matched subjects at the individual cellular level |
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44 | (3) |
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7 Proposal for future study |
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47 | (6) |
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53 | (1) |
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53 | (4) |
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3 Using mirror-image peptides to enhance robustness and reproducibility in studying the amyloid β-protein |
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57 | (14) |
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57 | (1) |
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2 Intrinsically disordered proteins and the challenge in studying their kinetics |
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58 | (1) |
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3 Biophysical characterization methods of the amyloid-β protein |
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59 | (1) |
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4 Potential sources of deviations from trends in fibril formation assays |
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60 | (1) |
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5 Mirror image Aβ to increase rigor in assessing quality of peptide preparations |
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61 | (3) |
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6 Kinetic timescale inconsistencies: Aβ40 vs. Aβ42 |
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64 | (1) |
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65 | (1) |
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65 | (6) |
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Section II Etiology of AD |
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4 In search of pathogenic amyloid β-peptide in familial Alzheimer's disease |
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71 | (8) |
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1 Why study familial Alzheimer's disease? |
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71 | (1) |
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2 Biology and pathobiology of γ-secretase |
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72 | (1) |
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73 | (1) |
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4 Processive proteolysis and FAD |
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74 | (1) |
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75 | (1) |
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76 | (1) |
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76 | (3) |
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5 Biology of splicing in Alzheimer's disease research |
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79 | (6) |
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79 | (1) |
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2 Altered mRNA splicing in the AD brain |
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80 | (1) |
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3 Long-read sequencing for precise identification of splicing variants |
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81 | (1) |
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4 Single-cell transcriptome analysis to overcome brain heterogeneity |
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81 | (1) |
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82 | (1) |
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83 | (1) |
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83 | (2) |
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6 Acquired cerebral amyloid angiopathy: An emerging concept |
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85 | (14) |
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86 | (1) |
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2 Early-onset CAA-related hemorrhages are associated with a history of neurosurgeries in childhood |
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86 | (1) |
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3 Incidental Ap pathology in iatrogenic Creutzfeldt-Jakob disease |
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87 | (3) |
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4 Molecular mechanisms underlying acquired CAA |
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90 | (3) |
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93 | (1) |
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93 | (1) |
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94 | (5) |
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Section III Neuroimmunology of AD |
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7 Blood-brain barrier and innate immunity in the pathogenesis of Alzheimer's disease |
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99 | (48) |
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1 Amyloid cascade hypothesis |
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102 | (4) |
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106 | (7) |
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3 Neurovascular unit, stroke, and AD |
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113 | (1) |
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114 | (2) |
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5 CAA and CMB in the development of AD and VCI |
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116 | (2) |
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6 Innate immunity in the pathogenesis of AD |
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118 | (2) |
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120 | (4) |
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124 | (2) |
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9 Glymphatic and lymphatic systems of the brain and AD |
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126 | (2) |
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10 Cholesterol as a risk factor |
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128 | (1) |
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11 Blood-based signatures of AD |
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129 | (1) |
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12 Neuron type-selective vulnerability and synapse loss |
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129 | (2) |
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131 | (1) |
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131 | (16) |
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8 Gut microbiota mediated allostasis prevents stress-induced neuroinflammatory risk factors of Alzheimer's disease |
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147 | (36) |
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148 | (2) |
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2 Physiological changes in response to chronic stress |
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150 | (2) |
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3 Stress-induced physiological changes predispose individuals to Alzheimer's disease |
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152 | (3) |
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4 Bidirectional stress regulation by the gut microbiota |
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155 | (4) |
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5 Stress-induced neuroinflammation drives Alzheimer's disease pathology |
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159 | (5) |
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6 Gut microbiota-derived metabolites prevent stress-induced neuroinflammation in Alzheimer's disease |
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164 | (8) |
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172 | (1) |
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173 | (10) |
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9 Neuroimmune interactions in Alzheimer's disease---New frontier with old challenges? |
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183 | (22) |
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1 Immune responses in neurodegenerative diseases early days |
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185 | (1) |
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2 Evidence for immune-overactivation in neurodegenerative diseases |
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186 | (1) |
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3 Immune exhaustion or inadequate immune responses in AD? |
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187 | (1) |
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4 Innate or adaptive immunity or both? |
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188 | (3) |
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5 Challenges moving forward |
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191 | (1) |
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192 | (1) |
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192 | (1) |
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192 | (13) |
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10 Alzheimer's therapy development: A few points to consider |
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205 | (14) |
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206 | (1) |
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2 Targeting tau intracellularly or extracellularly |
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207 | (3) |
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3 Drug-screening models: Preventing seeding/spread vs neurotoxicity |
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210 | (2) |
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4 Strains of Ap and tau: Influence on therapeutic development |
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212 | (2) |
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5 Targets other than Ap and tau |
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214 | (1) |
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215 | (1) |
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215 | (1) |
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216 | (3) |
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11 The next steps in curing Alzheimer's disease |
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219 | (4) |
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220 | (1) |
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220 | (3) |
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12 Future horizons in Alzheimer's disease research |
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223 | (20) |
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223 | (2) |
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2 Proteomic approaches to better understand the pathogenesis of AD |
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225 | (2) |
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3 Therapeutic approaches that target multiple oligomer species concurrently |
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227 | (3) |
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4 Targeting the major LOAD genetic risk factor: Apolipoprotein E4 |
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230 | (1) |
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5 Targeting innate immunity dysfunction in AD |
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231 | (2) |
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6 Testing alternative hypotheses of AD pathogenesis |
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233 | (1) |
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233 | (1) |
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234 | (1) |
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235 | (8) |
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13 Why delay in effective treatment for Alzheimer's disease and related conditions |
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243 | (14) |
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243 | (2) |
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2 Strategies to develop an effective treatment for a multifactorial disorder |
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245 | (7) |
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252 | (1) |
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252 | (5) |
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14 Restoring synaptic function through multimodal therapeutics |
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257 | (20) |
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Muhammad-AI-Mustafa Ismail |
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258 | (1) |
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2 Bringing back insulin and cholesterol metabolism balance for synaptic function |
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259 | (5) |
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3 Alleviation of Aβ and tau proteinopathies by autophagy enhancement to restore proteostasis and synaptic function |
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264 | (6) |
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4 The future of synaptic therapeutics in AD |
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270 | (1) |
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270 | (7) |
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15 Disease-modifying therapy for proteinopathies: Can the exception become the rule? |
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277 | (12) |
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280 | (3) |
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2 RNAi and antisense gene silencers |
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283 | (1) |
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284 | (1) |
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285 | (1) |
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285 | (4) |
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16 Combination therapy for Alzheimer's disease and related dementias |
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289 | (10) |
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289 | (2) |
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2 Limitations to a combination therapy approach to Alzheimer's disease |
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291 | (1) |
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3 What is Alzheimer's disease? |
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292 | (1) |
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4 Alternative strategies for the treatment of dementia---Focus on devices |
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293 | (3) |
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296 | (3) |
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Section V Alpha-synucleinopathies |
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17 Can infections trigger alpha-synucleinopathies? |
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299 | (24) |
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300 | (4) |
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2 Infections as potential triggers of alpha-synucleinopathies |
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304 | (9) |
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3 Research challenges regarding infections as triggers of Parkinson's disease |
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313 | (3) |
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316 | (1) |
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316 | (1) |
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316 | (7) |
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18 Prion-like propagation of α-synuclein in neurodegenerative diseases |
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323 | (28) |
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324 | (1) |
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325 | (1) |
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3 Pathogenic α-synuclein accumulation in patients' brains |
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326 | (1) |
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4 The "prion hypothesis" in neurodegenerative diseases |
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327 | (2) |
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5 In vitro experimental models of α-synuclein prion-like propagation |
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329 | (1) |
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6 In vivo experimental models of α-synuclein prion-like propagation |
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330 | (1) |
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7 Prion-like properties of pathogenic α-synuclein derived from patients with α-synucleinopathy |
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331 | (3) |
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8 Inactivation of pathogenic α-synuclein seeds |
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334 | (1) |
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9 α-Synuclein pathogenesis in multiple system atrophy |
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335 | (1) |
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10 What kind of α-synuclein species plays the key role in prion-like propagation? |
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336 | (1) |
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11 Applications of experimental models in the development of diagnostics and therapeutics |
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337 | (1) |
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12 Directions for future research |
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338 | (2) |
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340 | (11) |
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19 Yeast models of neurodegenerative diseases |
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351 | (22) |
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351 | (2) |
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2 Use Saccharomyces cerevisiae as a tractable model of human diseases |
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353 | (2) |
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3 Endogenous heritable yeast amyloids |
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355 | (3) |
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4 Developing yeast models of human neurodegenerative diseases |
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358 | (4) |
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5 Defining toxicity in a yeast-based ND model |
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362 | (2) |
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6 Impact of strain genotype: The background effect |
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364 | (2) |
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7 Yeast-based drug discovery |
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366 | (3) |
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8 Alternative yeast species: New models? |
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369 | (2) |
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9 Concluding remarks and future directions |
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371 | (2) |
| Acknowledgments |
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373 | (1) |
| References |
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373 | (8) |
| Index |
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