Re-examining tau-immunoreactive pathology in the population: granulovacuolar degeneration and neurofibrillary tangles. 2015

Sally Hunter, and Thais Minett, and Tuomo Polvikoski, and Elizabeta Mukaetova-Ladinska, and Carol Brayne, and
Department of Public Health and Primary Care, Institute of Public Health, Forvie Site, University of Cambridge School of Clinical Medicine, Box 113 Cambridge Biomedical Campus, Cambridge, CB2 0SP, UK. seh66@medschl.cam.ac.uk.

BACKGROUND Alzheimer's disease (AD) is associated with neurofibrillary pathology, including neurofibrillary tangles (NFT), neuritic plaques (NP) and neuropil threads containing aggregated microtubule associated protein tau. Aggregated tau is also associated with granulovacuolar degeneration (GVD). The relationships between tau, GVD, NFT and dementia are unclear. METHODS We assessed hippocampal (CA1) tau-immunoreactive GVD and NFT pathology in brain donations from the population-representative Cambridge City over 75s Cohort (CC75C) using the CERAD protocol and a modified protocol that included a morphological characterisation of tau-immunoreactive deposits within neurons as NFTs or as GVD. Associations between GVD, NFT and dementia were investigated. RESULTS Hippocampal pyramidal neurons affected with either NFT or GVD are common in the older population. Some tau-immunoreactive deposits resemble ghost GVD neurons. Tau immunoreactivity identified GVD in 95% cases rated as none with haematoxylin and eosin staining. Both severe NFT (odds ratio (OR) 7.33, 95% confidence interval (CI) 2.01; 26.80, p = 0.003) and severe GVD (OR 7.48, 95% (CI) 1.54; 36.24, p = 0.012) were associated with dementia status. Increasing NFT (OR 2.47 95% (CI) 1.45; 4.22, p = 0.001) and GVD (OR 2.12 95% (CI) 1.23; 3.64, p = 0.007) severities are associated with increasing dementia severity. However, when the analyses were controlled for other neuropathologies (NFT, NP, Tar-DNA binding Protein-43 and amyloid deposits), the associations between GVD and dementia lost significance. CONCLUSIONS Current neuropathological assessments do not adequately evaluate the presence and severity of the GVD pathology and its contribution to dementia remains unclear. We recommend that protocols to assess GVD should be developed for routine use and that tau, in a non-PHF associated conformation, is reliably associated with GVD.

UI MeSH Term Description Entries
D007150 Immunohistochemistry Histochemical localization of immunoreactive substances using labeled antibodies as reagents. Immunocytochemistry,Immunogold Techniques,Immunogold-Silver Techniques,Immunohistocytochemistry,Immunolabeling Techniques,Immunogold Technics,Immunogold-Silver Technics,Immunolabeling Technics,Immunogold Silver Technics,Immunogold Silver Techniques,Immunogold Technic,Immunogold Technique,Immunogold-Silver Technic,Immunogold-Silver Technique,Immunolabeling Technic,Immunolabeling Technique,Technic, Immunogold,Technic, Immunogold-Silver,Technic, Immunolabeling,Technics, Immunogold,Technics, Immunogold-Silver,Technics, Immunolabeling,Technique, Immunogold,Technique, Immunogold-Silver,Technique, Immunolabeling,Techniques, Immunogold,Techniques, Immunogold-Silver,Techniques, Immunolabeling
D008137 Longitudinal Studies Studies in which variables relating to an individual or group of individuals are assessed over a period of time. Bogalusa Heart Study,California Teachers Study,Framingham Heart Study,Jackson Heart Study,Longitudinal Survey,Tuskegee Syphilis Study,Bogalusa Heart Studies,California Teachers Studies,Framingham Heart Studies,Heart Studies, Bogalusa,Heart Studies, Framingham,Heart Studies, Jackson,Heart Study, Bogalusa,Heart Study, Framingham,Heart Study, Jackson,Jackson Heart Studies,Longitudinal Study,Longitudinal Surveys,Studies, Bogalusa Heart,Studies, California Teachers,Studies, Jackson Heart,Studies, Longitudinal,Study, Bogalusa Heart,Study, California Teachers,Study, Longitudinal,Survey, Longitudinal,Surveys, Longitudinal,Syphilis Studies, Tuskegee,Syphilis Study, Tuskegee,Teachers Studies, California,Teachers Study, California,Tuskegee Syphilis Studies
D008297 Male Males
D009410 Nerve Degeneration Loss of functional activity and trophic degeneration of nerve axons and their terminal arborizations following the destruction of their cells of origin or interruption of their continuity with these cells. The pathology is characteristic of neurodegenerative diseases. Often the process of nerve degeneration is studied in research on neuroanatomical localization and correlation of the neurophysiology of neural pathways. Neuron Degeneration,Degeneration, Nerve,Degeneration, Neuron,Degenerations, Nerve,Degenerations, Neuron,Nerve Degenerations,Neuron Degenerations
D009474 Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM. Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D003704 Dementia An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. Senile Paranoid Dementia,Amentia,Familial Dementia,Amentias,Dementia, Familial,Dementias,Dementias, Familial,Dementias, Senile Paranoid,Familial Dementias,Paranoid Dementia, Senile,Paranoid Dementias, Senile,Senile Paranoid Dementias
D005260 Female Females
D006624 Hippocampus A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation. Ammon Horn,Cornu Ammonis,Hippocampal Formation,Subiculum,Ammon's Horn,Hippocampus Proper,Ammons Horn,Formation, Hippocampal,Formations, Hippocampal,Hippocampal Formations,Hippocampus Propers,Horn, Ammon,Horn, Ammon's,Proper, Hippocampus,Propers, Hippocampus,Subiculums
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000369 Aged, 80 and over Persons 80 years of age and older. Oldest Old

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