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TDP-43 pathology in primary progressive aphasia and frontotemporal dementia with pathologic Alzheimer disease.

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.
AuthorsEileen 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
JournalActa neuropathologica (Acta Neuropathol) Vol. 120 Issue 1 Pg. 43-54 (Jul 2010) ISSN: 1432-0533 [Electronic] Germany
PMID20361198 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Apolipoprotein E4
  • DNA-Binding Proteins
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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