Advances in Alzheimer's and Parkinson's Disease: Insights, Progress, and Perspectives (Advances in Behavioral Biology)

a.pdf......Page 1
Advances in Behavioral Biology......Page 2
ADVANCES IN BEHAVIORAL BIOLOGY......Page 3
Advances in Alzheimer’sand Parkinson’s Disease......Page 4
Preface......Page 6
Contents......Page 7
Contributors......Page 12
Clinical Features of Dementia Associated With PD......Page 30
Cognitive Features......Page 31
Treatment of PDD......Page 32
References......Page 35
PARK1......Page 37
PARK2......Page 38
PARK3......Page 39
PARK6......Page 40
PARK8......Page 41
PARK9, PARK10, PARK11......Page 42
References......Page 43
Introduction......Page 45
Results......Page 46
References......Page 48
Introduction......Page 50
Clinical Research on Rehabilitation for PD......Page 51
Neurophysiological Approach to Motor Rehabilitation......Page 52
Possible Limitations of Rehabilitation for PD......Page 54
References......Page 55
Introduction......Page 58
References......Page 61
Introduction......Page 62
Current Diagnosis of Parkinson’s Disease......Page 63
From Neurochemical Findingshellip......Page 64
...To Pathological Staging.........Page 65
... En Route to Translation into Biomarkers......Page 66
Transcranial Ultrasonography......Page 67
Biochemical Markers......Page 68
Genetic Markers......Page 69
Conclusion......Page 70
References......Page 71
Cell Grafting for Parkinson’s Disease......Page 77
Neurotransmitter-Secreting Cell Line Grafting......Page 78
Simultaneous Delivery of Neurotransmitter and Neurotrophic Factor by Cell Line Grafting......Page 79
Control of Neurotransmitter and Neurotrophic Factor Secretion After Grafting into the Brain......Page 80
Conclusion......Page 81
References......Page 82
Introduction......Page 83
6-Hydroxydopamine......Page 84
MPTP......Page 85
Rotenone......Page 86
Continuous Administration of MPTP......Page 88
Genes Associated with Parkinson’s Disease and Genetic Models......Page 89
Parkin......Page 90
DJ-1......Page 91
a-Synuclein......Page 92
Inhibition of the UP System: One Cause of Parkinson’s Disease......Page 93
Novel Therapeutic Target in Parkinson’s Disease......Page 94
References......Page 95
Family D (Western Nebraska)......Page 100
Family A (German-Canadian)......Page 104
LRRK2/ROCO Gene......Page 107
G2019S Families......Page 108
Sagamihara Family......Page 109
Discussion......Page 110
References......Page 113
Introduction......Page 115
Activated Microglia in the Substantia Nigra, Putamen, and Various Regions of the Brain in PD......Page 116
Different Expression of Cytokines in the Hippocampus and Putamen in PD and LBD......Page 117
Conclusion......Page 118
References......Page 119
Introduction......Page 120
Antibodies and Immunohistochemistry......Page 122
Quantification of Immunoblots......Page 123
DJ-1 siRNA Transfection......Page 124
Symptomatic Mice Exhibit Elevated DJ-1 Levels......Page 125
DJ-1 Is Present in Reactive Astrocytes in Brain Sections from the Contursi Kindred......Page 126
DJ-1 Co-immunoprecipitates with Tau and Phospho-tau in Brain Homogenates......Page 128
DJ-1 siRNA Knockdown Confers Susceptibility to Oxidative Insult in Cell Culture......Page 129
Discussion......Page 130
References......Page 132
Introduction......Page 136
AB Deposition and the Neuroinflammatory Response in AD......Page 137
Neuroinflammation and Regenerative Pathways in AD......Page 138
Inflammation and the Pathological Cascade in AD......Page 139
Inflammation and the Pathological Cascade in PD......Page 140
Conclusions......Page 141
References......Page 142
IntroductionDue to the explosive growth in new information on the genetic and molecular pathology of the neurodegenerative diseases discussed here, which have been the subject of numerous reviews from many diverse perspectives, only a limited number of recent primary publications are listed and additional earlier literature citations are available in the recent reviews cited here.......Page 145
Alzheimer’s Disease and Related Tauopathies......Page 146
Parkinson’s Disease, Related Synucleinopathies, and Other Parkinsonian Movement Disorders......Page 148
References......Page 151
Neuronal Death in AD and PD......Page 154
Association of Oxidative Stress with Genetic Mutations and Risk Factors for AD and PD......Page 156
Primary Role of Oxidative Stress in AD and PD......Page 157
Cell Cycle Reentry in AD and PD......Page 159
Pathological Hallmarks: Pathogenic, Incidental, or a Beneficial Coping Response?......Page 160
Possible Protective Function of Abeta, Tau, and Alpha-Synuclein Against Oxidative Stress......Page 161
References......Page 163
Introduction......Page 170
Proteomics......Page 171
Alzheimer’s Disease......Page 175
Energy Dysfunction......Page 177
Lipid Abnormalities and Cholinergic Dysfunction......Page 178
Synaptic Abnormalities and LTP......Page 179
Parkinson’s Disease......Page 180
Redox Proteomics in PD......Page 181
Conclusions......Page 182
References......Page 183
Introduction......Page 189
Definitions......Page 190
Amyloid Fragments and Tau in AD......Page 191
Biomarkers in Body Fluids of PD Patients......Page 193
References......Page 194
Introduction......Page 195
Stereotactic Injections......Page 196
SBE-luc Reporter Mice......Page 197
Noninvasive Imaging of Endotoxic Brain Injury In Vivo......Page 199
References......Page 202
Introduction......Page 203
Alzheimer’ Disease Neuroimaging Initiative......Page 204
Study Outline......Page 205
Clinical Coordination Center......Page 206
Clinical Core......Page 207
Current State of the ADNI......Page 208
References......Page 209
Introduction......Page 210
Oxidative Stress, Oxidative Stress Signaling, and Alzheimer’s Disease......Page 211
Mitotic Abnormalities, Mitotic Signaling, and Alzheimer’s Disease......Page 213
Two-Hit Hypothesis......Page 214
Genetic Factors and the Two-Hit Hypothesis......Page 216
References......Page 217
Introduction......Page 224
Vascular Risk Factors in AD and MCI......Page 225
Conclusion......Page 227
References......Page 228
Cholesterol Homeostasis in the Brain......Page 229
Apolipoprotein E and Cholesterol Transport in the CNS: Backbone for the Maintenance of Synaptic Integrity and Plasticity......Page 231
Cholesterol Homeostasis and Cholesterol-Lowering Drugs......Page 232
References......Page 235
Introduction......Page 238
Lipids and Alzheimer’s Disease......Page 239
Cholesterol De Novo Synthesis Assay......Page 240
Identifying the Target Enzyme......Page 243
Conclusions......Page 244
References......Page 245
Introduction......Page 248
Synthesis and Physiological Functions of GAG......Page 249
Interactions of sGAG with b-Amyloid Peptide......Page 250
Interaction of sGAG with Prion Protein and Peptides......Page 252
Conclusions and Therapeutic Implications......Page 254
References......Page 258
Neuroprotective Role of Glycosaminoglycans......Page 263
Drugs and Chemicals......Page 265
Immunohistochemistry......Page 266
AF64A/Saline Administration......Page 267
AF64A/C3 Administration......Page 268
References......Page 269
Introduction......Page 271
Transdifferentiation of Adult Stem Cells......Page 272
Dedifferentiation of Adult Stem Cells......Page 274
APP Function in Stem Cell Biology......Page 275
References......Page 278
Introduction......Page 281
Production of AAV/Abibeta Vaccine......Page 282
Vaccination and Tissue Examinations......Page 283
Ab Vaccine-Mediated Meningoencephalitis......Page 284
Gut Immune System and Advantage of AAV/Abibeta Vaccine......Page 285
References......Page 287
Introduction......Page 289
Passive Immunization of Transgenic Mice with Phage-ScFv Against b-Amyloid Peptide......Page 290
Targeting b-Amyloid Plaques......Page 291
References......Page 293
Introduction......Page 295
AD Pathophysiology and BDNF Down-regulation......Page 296
Conclusions......Page 297
References......Page 298
Introduction......Page 300
NGF Receptor Levels in MCI and AD......Page 301
Pro-NGF Increases in MCI and AD......Page 302
Conclusions......Page 303
References......Page 304
Introduction......Page 306
Effects of Trophic Factors on Other Transcription Factors of the FoxO Family......Page 307
Tea Extracts Protect Hippocampal Neurons Through Their Catechins Gallate Esters......Page 308
Conclusion......Page 309
References......Page 310
Introduction......Page 312
Amyloid Cascade Hypothesis......Page 313
Intraneuronal Ab......Page 314
References......Page 316
a-Secretase Processing of betaAPP and PRPC......Page 320
bAPP and PRPC Physiological Processing: Up-regulation by PKC Agonists......Page 322
ADAM10 and ADAM17: Responsible for the Physiological Processing of betaAPP and PRPC?......Page 324
ADAM9: Indirect Contribution to betaAPP and PRPC Physiological Processing by Modulating ADAM10 Activity......Page 326
Conclusion......Page 327
References......Page 328
Background......Page 332
References......Page 337
Introduction......Page 340
Cell lines......Page 341
Aggregation of Tau in Cells......Page 342
Fragmentation of TauRD by a Thrombin-like Protease......Page 344
Aggregation and Toxicity......Page 345
Inhibition of Aggregation by Small Molecule Inhibitors......Page 346
Discussion......Page 348
References......Page 349
Introduction......Page 352
Tau Pathology in a Double Transgenic Mouse Overexpressing Tau Bearing Three of the Mutations Present in FTDP-17 (tauVLW) and GSK3 b......Page 353
Tau Pathology in a Double Transgenic Mouse Overexpressing Tau Bearing Three of the Mutations Present in FTDP-17 (TauVLW), and APP Bearing the Swedish Mutation (APPSW)......Page 354
Conclusion......Page 355
References......Page 356
Introduction......Page 358
Intracerebroventricular Injection of LPS......Page 359
Results......Page 360
Discussion......Page 365
Conclusion......Page 366
References......Page 367
Introduction......Page 369
Pleiotropic Effects of ApoE......Page 370
Pharmacogenetics......Page 375
CYP2D6 Polymorphisms in Alzheimer’s Disease......Page 377
References......Page 379
Disintegrin Metalloproteinase ADAM10 as alpha-Secretase In Vivo......Page 382
Activation of G Protein-Coupled Receptors and Downstream Signaling Systems......Page 383
Characterization of the Human ADAM10 Promoter and Up-regulation of Gene Expression by Retinoic Acid......Page 384
References......Page 386
Introduction......Page 388
Immunohistochemistry......Page 389
Frequency of AGD and TSA in AD......Page 390
Relation of AGD and TSA with 4R Tau Score in AD......Page 391
References......Page 392
Introduction......Page 393
Plasma Membrane as the Primary Target......Page 394
References......Page 396
Introduction......Page 399
Immunological Detection of GAb in Brain......Page 400
Background to GAb Generation in Brain......Page 401
GAb as Determinant for Area-Specific Deposition of Abeta......Page 402
References......Page 403
Neurotransmitter-Specific Structural Vulnerabilities to Extracellular Ab Burden......Page 405
Amyloid Dependent Neurotransmitter-Specific Dystrophic Neurite Generation......Page 408
References......Page 410
Cholinergic Changes in AD......Page 414
Glutamatergic Changes in AD......Page 416
References......Page 418
Introduction......Page 421
Immunotoxin Lesion of the nbm......Page 423
Cholinergic Therapy of Immunotoxin-Lesioned Animals......Page 425
Immunotoxin Lesion of the nbm......Page 426
Cholinergic Therapy of Immunotoxin-Lesioned Animals......Page 429
Conclusions......Page 430
References......Page 431
Introduction......Page 438
Effect of Ab on AChE Levels......Page 439
Role of a7 Nicotinic Acetylcholine Receptors in AD......Page 440
Cholinergic Neurites in AD Plaques......Page 441
Role of Cholinergic Neurons in Synaptic Scaling......Page 442
Conclusion......Page 443
References......Page 444
Introduction......Page 447
Effect of Muscarinic Cholinergic Receptor Stimulation on Nonamyloidogenic Metabolism of AbPP......Page 448
Effect of AChEIs on Expression and Metabolism of AbPP......Page 449
Evidence of Gene Expression Modulation by AChEIs......Page 450
References......Page 451
Introduction......Page 453
Lipophilicity Determination......Page 455
Ab Assay......Page 456
Phenserine, Cymserine, and Physostigmine Assessed at Nontoxic Doses in Human Neuronal (SK-N-SH) Cell Cultures......Page 457
Differential Effects of Phenserine, Cymserine, and Physostigmine on Soluble APP Levels......Page 458
Differential Effects of Phenserine, Cymserine, and Physostigmine on Soluble Ab......Page 459
Effects of Phenserine and Physostigmine on Cholinesterase Inhibition......Page 460
Pharmacologic Properties of Three Closely Related Carbamate Drugs......Page 461
Discussion......Page 462
Conclusion......Page 466
References......Page 467
Introduction......Page 471
Fluorescent Imaging Plate Reader......Page 472
Patch-Clamp Recordings in Cultured Hippocampal Neurons......Page 473
CNS Selective nAChRs Potentiators......Page 474
Selective ba7 nAChR Potentiators......Page 476
Discussion......Page 477
References......Page 479
Index......Page 481