Neuropathological features of frontotemporal dementia and parkinsonism linked to chromosome 17q21-22 (FTDP-17): Duke Family 1684
| Autor: | M. G. Spillantini, Kathleen A. Welsh-Bohmer, A. D. Roses, Donald E. Schmechel, Christine M. Hulette, R. A. Crowther, P. C. Gaskell, Margaret A. Pericak-Vance, Larry H. Yamaoka |
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| Rok vydání: | 1999 |
| Předmět: |
Adult
Male Pathology medicine.medical_specialty Microtubule-associated protein Immunoelectron microscopy Tau protein tau Proteins Biology Pathology and Forensic Medicine Cellular and Molecular Neuroscience Limbic system mental disorders medicine Dementia Humans Age of Onset Ubiquitins Aged Parkinsonism Parkinson Disease Sarcosine General Medicine Middle Aged medicine.disease Immunohistochemistry Temporal Lobe Frontal Lobe Pedigree Microscopy Electron medicine.anatomical_structure Phenotype Neurology Gliosis biology.protein Female Neurology (clinical) medicine.symptom Frontotemporal dementia Chromosomes Human Pair 17 |
| Zdroj: | Journal of neuropathology and experimental neurology. 58(8) |
| ISSN: | 0022-3069 |
| Popis: | Frontotemporal dementia with parkinsonism (FTDP-17) is an autosomal dominant disorder that presents clinically with dementia, extrapyramidal signs, and behavioral disturbances in mid-life and progresses to death within 5 to 10 years. Pathologically, the disorder is characterized by variable neuronal loss and gliosis in the frontal and temporal lobes, limbic structures, and the midbrain. Autopsied individuals from some kindreds display abundant neurofibrillary change while others, including a single affected individual from Duke Family 1684, lack distinctive histological features and exhibit only mild neuronal loss and gliosis in limbic structures and subcortical nuclei when examined by routine silver stain. Recently, mutations in the microtubule associated protein tau have been shown to segregate with the disease in this family and in many other affected kindreds. In order to examine the distribution of tau deposits, we performed tau immunohistochemistry, immunoblotting, and immunoelectron microscopy of tau-containing filaments. Immunohistochemistry revealed numerous tau deposits within glial cells and within neurons. Twisted ribbon-like filaments observed by immunoelectron microscopy were immunodecorated with tau AT8 antibody. Sarkosyl-insoluble tau extracted from the hippocampus and cortex migrated as 2 major bands at 64 and 68 kilodaltons and a minor band at 72 kilodaltons, which after alkaline phosphatase treatment appeared to contain mainly tau isoforms with 4 repeats. Furthermore, the ratio of soluble tau with 4 to 3 microtubule-binding repeats was increased. The role of tau mutations in this disorder is discussed in this paper. |
| Databáze: | OpenAIRE |
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