Cerebral Cortex

1 Cognitive Profiles of Normal Human Aging.- 1. Introduction.- 2. Domains of Cognitive function.- 3. Memory.- 3.1. Types of Memory.- 3.2. Explicit Memory Performance and Aging.- 3.3. Implicit Memory Performance and Aging.- 4. Executive function.- 5. Visuospatial function.- 6. Language.- 7. Attention.- 8. General Intelligence.- 9. Age-Related Changes in Brain Structure and function.- 10. Conclusion.- 11. References.- 2 Age-Related Cognitive Decline in the Rhesus Monkey.- 1. Introduction.- 2. Life Span of the Rhesus Monkey.- 3. Cognitive function.- 3.1. Attention.- 3.2. Learning and Memory.- 3.3. Executive System function.- 3.4. Motor Skills.- 4. Performance Patterns.- 5. Longitudinal Studies.- 6. Neurobiological Considerations.- 7. Conclusions.- 8. References.- 3 Normal Aging in the Cerebral Cortex of Primates.- 1. Introduction.- 2. Neurons in the Cerebral Cortex.- 3. Variation in the Sizes of Cortical Areas.- 4. Changes in Volume: Gray and White Matter with Age.- 5. Effects of Age on Dendrites.- 6. Effects of Age on Layer I.- 7. Age-Related Changes in Synapses.- 8. Effects of Aging on Axons and Their Sheaths.- 9. Effects of Aging on Neuroglial Cells.- 10. Neuritic Plaques and Amyloid.- 11. Conclusions.- 12. References.- 4 Age-Related Neuronal Loss in the Cerebral Cortex.- 1. Background.- 1.1. Historical Confusion.- 1.2. A More Clear but Still Incomplete View.- 2. Recent Studies with Improved Methods.- 3. Differences in Neuronal Loss Patterns: Normal Aging and Alzheimer's Disease.- 4. Interspecies Differences.- 5. Factors other than Neuronal Loss.- 6. The Emerging View and Its Implications.- 7. References.- 5 Age-Related Cognitive Deficits and Neurotransmitters: The Role of Catecholamine Mechanisms in Prefrontal Cortical Cognitive Decline.- 1. Introduction.- 2. Pattern of Cognitive Deficits with Normal Aging.- 2.1. Monkeys.- 2.2. Humans.- 3. Pattern of Neuropathological and Neurochemical Changes.- 3.1. Neuropathological Changes.- 3.2. Neurochemical Changes.- 4. Neurotransmitter Modulation of the Prefrontal Cortex.- 4.1. Dopamine.- 4.2. Norepinephrine.- 4.3. Serotonin.- 4.4. Acetylcholine.- 5. The Cholinergic Hypothesis of Age-Related Cognitive Decline.- 6. Functional Evidence for PFC Catecholamine Loss with Age.- 6.1. Dopamine Loss.- 6.2. Norepinephrine Loss.- 7. Summary.- 8. References.- 6 Neurotransmitter Receptor Changes in the Hippocampus and Cerebral Cortex in Normal Aging.- 1. Introduction.- 2. Technical Considerations.- 3. Age-Related Changes in Cholinergic Receptors.- 4. Age-Related Changes in GABAergic Receptors.- 5. Age-Related Changes in Glutamatergic Receptors.- 6. Age-Related Changes in Monkey Temporal Lobe.- 7. Possible Mechanisms of Receptor Changes.- 7.1. Membrane Loss.- 7.2. Functional or Metabolic Down-Regulation.- 7.3. Masking of Loss by Up-Regulation.- 7.4. Changes in Affinity and Gene Regulation of Subunits.- 8. Summary and Conclusions.- 9. References.- 7 Trophic Factors in Experimental Models of Adult Central Nervous System Injury.- 1. Introduction.- 1.1. The Trophic Hypothesis.- 1.2. Trophic Factor Diversity.- 1.3. Trophic Influence Assessment in Vivo.- 2. Experimental Approaches.- 2.1. Injury Models.- 2.2. Trophic Factor Delivery Systems.- 3. Nerve Growth Factor.- 3.1. Nerve Growth Factor and Its Receptors.- 3.2. In Vitro Activity.- 3.3. In Vivo Activity.- 3.4. Clinical Experience with Nerve Growth Factor Administration.- 4. Other Neurotrophins.- 4.1. Neurotrophins and Their Receptors.- 4.2. In Vitro Activity.- 4.3. In Vivo Activity.- 4.4. Clinical Experience with Neurotrophin Administration.- 5. Ciliary Neurotrophic Factor.- 6. Fibroblast Growth Factors.- 6.1. Fibroblast Growth Factors and Their Receptors.- 6.2. In Vitro Activity.- 6.3. In Vivo Activity.- 7. Trophic Factor Administration and Adult Neurogenesis.- 7.1. In Vitro Evidence.- 7.2. In Vivo Evidence.- 8. Conclusions.- 8.1. Reliability of Phenotypic Expression.- 8.2. Caveats Regarding Quantification of Tissue Sections.- 8.3. Broad Effects of Trophic Factor Administration.- 9. References.- 8 Cortical Neuropathology in Aging and Dementing Disorders: Neuronal Typology, Connectivity, and Selective Vulnerability.- 1. Introduction.- 2. Neuropathological Evidence of Selective Neuronal Vulnerability in Aging and Alzheimer's Disease.- 2.1. Neuropathological Changes.- 2.2. Distribution of Cortical Neurofibrillary Tangles and Senile Plaques.- 2.3. Correlations between Lesion Distribution and Specific Circuits.- 3. Morphologic and Neurochemical Correlates of Neuronal Vulnerability in AD.- 3.1. Neuronal Types and Development of Neurofibrillary Tangles.- 3.2. Abundance of Nonphosphorylated Neurofilament Protein in Subsets of Vulnerable Neurons.- 3.3. Glutamate Receptor Implication.- 3.4. Other Proteins Associated with Neuronal Degeneration.- 3.5. Morphologic and Molecular Characteristics of Resistant Neuron Subpopulations.- 4. Other Dementing Disorders: Evidence for Disease-Specific Involvement of Cortical Circuitry.- 4.1. Down's Syndrome.- 4.2. Guamanian Amyotrophic Lateral Sclerosis/Parkinsonism-Dementia Complex.- 4.3. Progressive Supranuclear Palsy and Corticobasal Degeneration.- 4.4. Postencephalitic Parkinsonism.- 4.5. Dementia Pugilistica and Posttraumatic Dementia.- 4.6. Pick's Disease.- 4.7. Frontal Lobe Dementia.- 4.8. Lewy Body Dementia.- 4.9. Other Neurodegenerative Disorders Involving Cytoskeletal Alterations.- 5. Conclusions and Future Prospects.- 6. References.- 9 The Anatomy of Dementias.- 1. Introduction.- 2. Alzheimer's Disease and the Primary Involvement Pattern of the Temporal Lobe.- 3. Progressive Subcortical Gliosis.- 4. Dementia of the Frontal Type.- 5. Pick's Disease.- 6. Huntington's Disease.- 7. Parkinson's Disease and Diffuse Lewy Body Disease.- 8. Corticobasal Degeneration.- 9. Multiple System Atrophy.- 10. Progressive Supranuclear Palsy.- 11. Schizophrenia.- 12. Discussion.- 12.1. General.- 12.2. Alzheimer's Disease and Progressive Subcortical Gliosis: Head Brain /Body Brain and Architectonics.- 12.3. Embryology of the Cerebral Cortex and Progressive Subcortical Gliosis.- 12.4. Frontal-Type Dementia, Pick's Disease, and the Selective Vulnerability of the Frontal and Temporal Lobes.- 12.5. Huntington's Disease and Diffuse Lewy Body Disease: Dementias with Cerebral Cortical Pathology and Prominent Subcortical Changes.- 12.6. Corticobasal Degeneration, Multiple System Atrophy, and Progressive Supranuclear Palsy: Dementias with Predominately Subcortical Involvement.- 12.7. Schizophrenia.- 12.8. Conclusion.- 13. References.- 10 Age-Related Changes in Subcortical Nuclei that Project to the Cerebral Cortex.- 1. Introduction.- 2. Subcortical Areas.- 2.1. Cholinergic Basal Forebrain.- 2.2. Dopaminergic Ventral Mesencephalon.- 2.3. Locus Coeruleus.- 2.4. Median and Dorsal Raphe Nuclei.- 3. Discussion.- 3.1. Age-Related Changes.- 3.2. Disease-Related Changes.- 4. Summary and Conclusions.- 5. References.- 11 Ultrastructural Changes in Dementing Illnesses.- 1. Introduction.- 2. Alzheimer's Disease.- 2.1. Alzheimer's Neurofibrillary Tangles.- 2.2. Ghost Tangles.- 2.3. Astrocytic Paired Helical Filaments.- 2.4. Anchorage Densities of Perivascular Astrocytes.- 2.5. Senile Plaques.- 2.6. Hirano Bodies (Eosinophilic Rodlike Structures).- 2.7. Granulovacuolar Degeneration.- 3. Pick's Disease.- 4. Progressive Supranuclear Palsy and Corticobasal Degeneration.- 4.1. Progressive Supranuclear Palsy.- 4.2. Corticobasal Degeneration.- 5. Diffuse Lewy Body Disease.- 6. Cruetzfeldt-Jakob Disease.- 7. Amyotrophic Lateral Sclerosis with Dementia.- 8. AIDS-Dementia Complex.- 9. Conclusion.- 10. References.- 12 Locating Genetic Modifiers for Inherited Neurodegenerative Diseases.- 1. Introduction.- 2. Conceptualization of Genetic Modifiers.- 3. Wilson's Disease.- 4. Huntington's Disease.- 5. Machado-Joseph Disease.- 6. Approaches for Identifying Genetic Modifiers.- 6.1. Genetic Case-Control Paradigms.- 6.2. Genetic Linkage Analysis.- 6.3. Special Case: Primary Mutation and Its Modifier in One Genetic System.- 7. Conclusions.- 8. References.- 13 Early Features of Alzheimer's Disease.- 1. Introduction.- 2. Memory Changes in Early Alzheimer's Disease.- 3. Executive Function Changes in Early Alzheimer's Disease.- 4. Changes in Brain Structure and Function in Early Alzheimer's Disease that May Underly the Memory Deficit.- 5. Changes in Brain Structure in Early Alzheimer's Disease Related to Executive Function Deficits.- 6. Summary.- 7. References.- 14 Temporal Sequence of Alzheimer's Disease-Related Pathology.- 1. Introduction.- 2. Anatomical Considerations.- 3. Extracellular Amyloid Deposits.- 3.1. Transiently Developed Forms of Amyloid Deposits.- 3.2. Mature Forms of Amyloid Deposits.- 3.3. Evolutionary Stages of A?-Amyloid Deposition.- 4. Intraneuronal Neurofibrillary Changes.- 4.1. Neurofibrillary Tangles, Neuropil Threads, and Neuritic Plaques.- 4.2. Evolutionary Stages of Neurofibrillary Tangles and Neuropil Threads.- 4.3. Stages I to VI: Development Repeats Cortical Myelination Progression in Reverse Order.- 5. Age, Amyloid Deposits, and Neurofibrillary Changes.- 6. References.- 15 Neuropathological Correlates of Dementia in Alzheimer's Disease.- 1. Introduction.- 1.1. Synapse Formation and Remodeling as the Microanatomical Correlate of Cognition.- 1.2. Pre- and Postsynaptic Damage as the Basis for Dementia.- 1.3. Approaches to Understanding the Structural Basis of Alzheimer's Disease Dementia.- 2. Neuropathological Basis for Cognitive Decline in Alzheimer's Disease.- 2.1. Characteristics of the Neurodegenerative Process.- 2.2. Clinico-Neuropathological Correlation in Alzheimer's Disease and Related Disorders.- 2.3. Correlations with the Progression of Neurodegenerative Alterations.- 2.4. Correlations with Neuropathological Markers.- 2.5. Correlations with Neurofibrillary Cytoskeletal Alterations.- 2.6. Association with Lewy Bodies.- 2.7. Correlations with Amyloid Deposition.- 3. Mechanisms of Synaptic Pathology in Alzheimer's Disease.- 3.1. Amyloid-? Precursor Protein and Synaptic Damage.- 3.2. Apolipoprotein E and Synaptic Damage.- 3.3. Non-A? Component Precursor and Presynaptic Damage.- 4. References.- 16 Multifocal Cortical Neurodegeneration in Alzheimer's Disease.- 1. Introduction.- 2. Neuropsychological Subgroups.- 3. Genetic Factors: Subgroups or Subtypes?.- 3.1. Frank Genetic Subtypes: Autosomal Dominant Mutations.- 3.2. Different Clinical and Neuropathological Outcomes: PS and APP Mutations.- 3.3. Mitochondrial DNA Mutations.- 3.4. Genetic Risk Factor: The ApoE Gene.- 4. Models of Heterogeneity, Postmortem Measures, and A? Neurotoxicity.- 5. Laminar Patterns in Neocortical Neurochemistry.- 6. Laminar Patterns of Neuron Vulnerability in Frontal/Anterior Cingulate Dementias.- 7. Multifocal Atrophies and Subsystem Disruption in Alzheimer's Disease.- 7.1. Frontotemporal Atrophy and Case FG.- 7.2. Parietotemporal Atrophy and Case WJ.- 7.3. Posterior Cortical Atrophy.- 8. Layer-Selective Neurodegeneration in Posterior Cingulate Cortex.- 9. Neocortical Neurochemistry and the Subtypes Hypothesis.- 10. Models of Multifocal Cortical Neurodegeneration and the Subtypes Hypothesis.- 11. References.- 17 Molecular Pathology of Alzheimer's Disease and Related Disorders.- 1. Introduction.- 2. Genetics of Familial Alzheimer's Disease and Sporadic Alzheimer's Disease.- 2.1. Familial Alzheimer's Disease Caused by Mutations in the Amyloid-? Precursor Protein and Presenilin Genes.- 2.2. ApoE as a Risk Factor for Alzheimer's Disease.- 3. Neurofibrillary Tangles: Pathophysiological Alterations in Hippocampus and Neocortex.- 3.1. Tau Structure and function.- 3.2. Paired Helical Filament Tau Structure and Localization to Neurofibrillary Tangles and Dystrophic Processes in Alzheimer's Disease.- 3.3. Neurofibrillary Pathology in Other Tangle-Bearing Diseases.- 4. Senile Plaques: Pathophysiological Alterations in Hippocampus and Neocortex.- 4.1. Amyloid Deposition and Alzheimer's Disease.- 4.2. Amyloid Deposition and Other Neurological Disorders.- 4.3. Genetics and Proteolytic Processing of Amyloid-? Precursor Protein and Amyloid-? Protein.- 4.4. Function of Amyloid-? Protein.- 5. Other Lesions and Cytopathology: Pathology in Hippocampus and Neocortex.- 5.1. Hirano Bodies.- 5.2. AMY Plaques.- 5.3. Granulovacuolar Degeneration.- 5.4. Nonneuronal Cells and Inflammatory Changes in Alzheimer's Disease.- 6. Analysis of Vulnerable Cell Types and Pathological Lesions in Diseased Brain.- 6.1. Cell Death in Alzheimer's Disease.- 6.2. Elucidating Pathologic Mechanisms: RNA Species Assessment in Alzheimer's Disease Lesions.- 6.3. mRNA Species in Single Profiles Isolated from the Alzheimer's Disease Hippocampus.- 7. Conclusions.- 8. References.- 18 Glutamate Receptors and Excitotoxic Mechanisms in Alzheimer's Disease.- 1. Introduction.- 2. Components of Glutamatergic Pathways.- 2.1. The Ionotropic Receptors.- 2.2. The Metabotropic Glutamate Receptors.- 2.3. The Transporters.- 3. Alzheimer's Disease Neuropathology.- 4. Alterations in Glutamatergic Pathways in Alzheimer's Disease.- 4.1. The NMDA Receptors.- 4.2. The Kainic Acid Receptors.- 4.3. The AMPA Receptors.- 4.4. The Metabotropic Receptors.- 4.5. In Situ Hybridization Studies of Glutamate Receptors.- 4.6. Immunohistochemical Studies of Glutamate Receptors.- 4.7. Glutamate Levels.- 4.8. Glutamate Transport.- 5. Glutamate Receptors and Excitotoxic Insult.- 6. Relationship between Glutamatergic Pathways and Alzheimer's Disease Pathology?.- 7. Summary and Conclusions.- 8. References.- 19 Nerve Growth Factor Systems in Alzheimer's Disease.- 1. Introduction.- 2. Nerve Growth Factor Receptor Subtypes.- 3. Nerve Growth Factor in Neurological Disease.- 4. Nerve Growth Factor Protein Levels in Normal Aged Human Brain.- 5. Nerve Growth Factor-Like Immunoreactivity in Hippocampus.- 6. Target-Derived Nerve Growth Factor within Aged Cholinergic Basal Forebrain Neurons.- 7. Nerve Growth Factor Receptors and Cholinergic Basal Forebrain Neurons.- 8. Low-Affinity p75NTR and High-Affinity trkA Receptor within the Basal Forebrain.- 9. Colocalization of p75NTR and trk within the Primate Basal Forebrain.- 10. Alterations in the Nerve Growth Factor System in Alzheimer's Disease.- 10.1. Cytoskeletal Abnormalities within p75NTR Containing Cholinergic Basal Forebrain Neurons.- 10.2. Loss of p75NTR Protein- and mRNA-Containing Cholinergic Basal Forebrain Neurons.- 11. Altered Transport of Target-Derived Nerve Growth Factor.- 12. Increased Nerve Growth Factor Levels in Neo- and Limbic Cortex.- 13. trkA within Cholinergic Basal Forebrain Neurons.- 13.1. Alterations in trkA Gene and Protein Expression in Nucleus Basalis.- 13.2. Reverse Transcription Polymerase Chain Reaction and Western Blot Analysis of trkA.- 13.3. Is Nerve Growth Factor Off trk in Alzheimer's Disease?.- 14. Neuroplasticity of the Nerve Growth Factor Receptor System in Alzheimer's Disease.- 14.1. De Novo Expression of p75NTR Containing Cortical Neurons.- 14.2. Galanin Fiber Hypertrophy of Remaining p75NTR Basal Forebrain Neurons.- 15. Treatment Approaches for Preventing Cholinergic Cell Degeneration in Alzheimer's Disease.- 15.1. Grafting Encapsulated Cells Secreting Human Nerve Growth Factor.- 15.2. Comments.- 16. Nerve Growth Factor Conjugated to an Antitransferrin Receptor Antibody.- 16.1. Actions of OX-26-NGF on Cholinergic Systems.- 16.2. OX-26-NGF Prevents Cholinergic Basal Forebrain Cell Degeneration in Animal Correlates of Alzheimer's Disease.- 17. Conclusion.- 18. References.- 20 Vascular-Related and Mediated Alterations in Alzheimer's Disease.- 1. Introduction.- 2. Imaging the Vasculature.- 3. Macroscopic Changes in the Vasculature.- 4. Microscopic Changes in the Vasculature.- 5. Pathologic Deposition in the Vasculature.- 6. Evidence for Vascular-Mediated Alterations.- 7. References.