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Journal article
Microglial activation and TDP-43 pathology correlate with executive dysfunction in amyotrophic lateral sclerosis
Acta neuropathologica, v 123(3), pp 395-407
01 Mar 2012
PMID: 22210083
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
While cognitive deficits are increasingly recognized as common symptoms in amyotrophic lateral sclerosis (ALS), the underlying histopathologic basis for this is not known, nor has the relevance of neuroinflammatory mechanisms and microglial activation to cognitive impairment (CI) in ALS been systematically analyzed. Staining for neurodegenerative disease pathology, TDP-43, and microglial activation markers (CD68, Iba1) was performed in 102 autopsy cases of ALS, and neuropathology data were related to clinical and neuropsychological measures. ALS with dementia (ALS-D) and ALS with impaired executive function (ALS-Ex) patients showed significant microglial activation in middle frontal and superior or middle temporal (SMT) gyrus regions, as well as significant neuronal loss and TDP-43 pathology in these regions. Microglial activation and TDP-43 pathology in middle frontal and superior or middle temporal regions were highly correlated with measures of executive impairment, but not with the MMSE. In contrast, only one ALS-D patient showed moderate Alzheimer's disease (AD) pathology. Tau and A beta pathology increased with age. A lower MMSE score correlated with tau pathology in hippocampus and SMT gyrus, and with A beta pathology in limbic and most cortical regions. Tau and A beta pathology did not correlate with executive measures. We conclude that microglial activation and TDP-43 pathology in frontotemporal areas are determinants of FTLD spectrum dementia in ALS and correlate with neuropsychological measures of executive dysfunction. In contrast, AD pathology in ALS is primarily related to increasing age and associated with a poorer performance on the MMSE.
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Details
- Title
- Microglial activation and TDP-43 pathology correlate with executive dysfunction in amyotrophic lateral sclerosis
- Creators
- Johannes Brettschneider - University of PennsylvaniaDavid J. Libon - Drexel UniversityJon B. Toledo - University of PennsylvaniaSharon X. Xie - University of PennsylvaniaLeo McCluskey - University of PennsylvaniaLauren Elman - University of PennsylvaniaFelix Geser - Universität UlmVirginia M. -Y. Lee - College Station Medical CenterMurray Grossman - University of PennsylvaniaJohn Q. Trojanowski - University of Pennsylvania
- Publication Details
- Acta neuropathologica, v 123(3), pp 395-407
- Publisher
- Springer Nature
- Number of pages
- 13
- Grant note
- AG033101; AG17586; AG10124; AG32953 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Wyncote Foundation Fundacion Alfonso Martin Escudero P01AG032953 / NATIONAL INSTITUTE ON AGING; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA) AOBJ586910 / Deutsche Forschungsgemeinschaft DFG; German Research Foundation (DFG) Koller Family Foundation
- Resource Type
- Journal article
- Language
- English
- Web of Science ID
- WOS:000301856300006
- Scopus ID
- 2-s2.0-84857918252
- Other Identifier
- 991021901314404721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Clinical Neurology
- Neurosciences
- Pathology