额颞叶变性
精神分裂症(面向对象编程)
医学
病态的
病理
精神科
内科学
失智症
痴呆
疾病
作者
Felix Geser,John Robinson,Joseph A. Malunda,Sharon X. Xie,Chris Clark,Linda K. Kwong,Paul J. Moberg,Erika M. Moore,Vivianna M. Van Deerlin,Virginia M.‐Y. Lee,Steven E. Arnold,John Q. Trojanowski
出处
期刊:Archives of neurology
[American Medical Association]
日期:2010-10-01
卷期号:67 (10)
被引量:92
标识
DOI:10.1001/archneurol.2010.254
摘要
Background
Major psychiatric diseases such as schizophrenia and mood disorders have not been linked to a specific pathology, but their clinical features overlap with some aspects of the behavioral variant of frontotemporal lobar degeneration. Although the significance of pathological 43-kDa (transactivation response) DNA-binding protein (TDP-43) for frontotemporal lobar degeneration was appreciated only recently, the prevalence of TDP-43 pathology in patients with severe mental illness vs controls has not been systematically addressed. Objective
To examine patients with chronic psychiatric diseases, mainly schizophrenia, for evidence of neurodegenerative TDP-43 pathology in comparison with controls. Design
Prospective longitudinal clinical evaluation and retrospective medical record review, immunohistochemical identification of pathological TDP-43 in the central nervous system, and genotyping for gene alterations known to cause TDP-43 proteinopathies including the TDP-43 (TARDBP) and progranulin (GRN) genes. Setting
University health system. Participants
One hundred fifty-one subjects including 91 patients with severe mental illness (mainly schizophrenia) and 60 controls. Main Outcome Measures
Clinical medical record review, neuronal and glial TDP-43 pathology, andTARDPandGRNgenotyping status. Results
Significant TDP-43 pathology in the amygdala/periamygdaloid region or the hippocampus/transentorhinal cortex was absent in both groups in subjects younger than 65 years but present in elderly subjects (29% [25 of 86] of the psychiatric patients and 29% [10 of 34] of control subjects). Twenty-three percent (8 of 35) of the positive cases showed significant TDP-43 pathology in extended brain scans. There were no evident differences between the 2 groups in the frequency, degree, or morphological pattern of TDP-43 pathology. The latter included (1) subpial and subependymal, (2) focal, or (3) diffuse lesions in deep brain parenchyma and (4) perivascular pathology. A newGRNvariant of unknown significance (c.620T>C, p.Met207Thr) was found in 1 patient with schizophrenia with TDP-43 pathology. No knownTARDBPmutations or other variants were found in any of the subjects studied herein. Conclusions
The similar findings of TDP-43 pathology in elderly patients with severe mental illness and controls suggest common age-dependent TDP-43 changes in limbic brain areas that may signify that these regions are affected early in the course of a cerebral TDP-43 multisystem proteinopathy. Finally, our data provide an age-related baseline for the development of whole-brain pathological TDP-43 evolution schemata.
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