Abstract |
The clinical syndrome of primary progressive aphasia (PPA) can be associated with a variety of neuropathologic diagnoses at autopsy. Thirty percent of cases have Alzheimer disease (AD) pathology, most often in the usual distribution, which defies principles of brain-behavior organization, in that aphasia is not symptomatic of limbic disease. The present study investigated whether concomitant TDP-43 pathology could resolve the lack of clinico-anatomic concordance. In this paper, 16 cases of clinical PPA and 10 cases of primarily non-aphasic frontotemporal dementia (FTD), all with AD pathology, were investigated to determine whether their atypical clinical phenotypes reflected the presence of additional TDP-43 pathology. A comparison group consisted of 27 cases of pathologic AD with the typical amnestic clinical phenotype of probable AD. Concomitant TDP-43 pathology was discovered in only three of the FTD and PPA but in more than half of the typical amnestic clinical phenotypes. Hippocampal sclerosis (HS) was closely associated with TDP-43 pathology when all groups were combined for analysis. Therefore, the clinical phenotypes of PPA and FTD in cases with pathologic AD are only rarely associated with TDP-43 proteinopathy. Furthermore, medial temporal TDP-43 pathology is more tightly linked to HS than to clinical phenotype. These findings challenge the current notions about clinicopathologic correlation, especially about the role of multiple pathologies.
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Authors | Eileen H Bigio, Manjari Mishra, Kimmo J Hatanpaa, Charles L White 3rd, Nancy Johnson, Alfred Rademaker, Bing Bing Weitner, Han-Xiang Deng, Steven D Dubner, Sandra Weintraub, Marsel Mesulam |
Journal | Acta neuropathologica
(Acta Neuropathol)
Vol. 120
Issue 1
Pg. 43-54
(Jul 2010)
ISSN: 1432-0533 [Electronic] Germany |
PMID | 20361198
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Apolipoprotein E4
- DNA-Binding Proteins
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Topics |
- Aged
- Alzheimer Disease
(genetics, metabolism, pathology)
- Aphasia, Primary Progressive
(genetics, metabolism, pathology)
- Apolipoprotein E4
(genetics, metabolism)
- Brain
(metabolism, pathology)
- DNA-Binding Proteins
(metabolism)
- Female
- Frontotemporal Dementia
(genetics, metabolism, pathology)
- Gliosis
(genetics, metabolism, pathology)
- Hippocampus
(metabolism, pathology)
- Humans
- Male
- Middle Aged
- Neurons
(metabolism, pathology)
- Organ Size
- Phenotype
- Sclerosis
(genetics, metabolism, pathology)
- TDP-43 Proteinopathies
(genetics, metabolism, pathology)
- Temporal Lobe
(metabolism, pathology)
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