Abstract | OBJECTIVE: METHODS: Brain tissue from a 65-year-old patient with PPA and progranulin mutation was analyzed using immunohistochemical methods for TDP-43. Analysis was performed in the superior temporal gyrus, inferior temporal gyrus, inferior parietal lobule, orbitofrontal cortex, entorhinal cortex, and dentate gyrus. Neuronal intranuclear inclusions, neuronal cytoplasmic inclusions, and dystrophic neurites were quantified using modified stereologic analysis. Analysis of variance was used to determine significant effects. RESULTS: All 3 types of inclusions predominated on the left side of analyzed cortical regions. They were also more frequent in language areas than in memory-related areas. CONCLUSION: These results demonstrate a phenotypically concordant distribution of abnormal TDP-43 inclusions in primary progressive aphasia (PPA). This contrasts with PPA cases with Alzheimer pathology where no consistent leftward asymmetry of neurofibrillary degeneration or amyloid deposition has been demonstrated despite the leftward asymmetry of the atrophy, and where neurofibrillary tangles show a greater density in memory than language areas despite the predominantly aphasic phenotype. This case suggests that the TDP-43 inclusions in PPA- frontotemporal lobar degeneration are more tightly linked to neuronal death and dysfunction than neurofibrillary and amyloid deposits in PPA- Alzheimer disease.
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Authors | G Gliebus, E H Bigio, K Gasho, M Mishra, D Caplan, M-M Mesulam, C Geula |
Journal | Neurology
(Neurology)
Vol. 74
Issue 20
Pg. 1607-10
(May 18 2010)
ISSN: 1526-632X [Electronic] United States |
PMID | 20479359
(Publication Type: Case Reports, Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- DNA-Binding Proteins
- GRN protein, human
- Intercellular Signaling Peptides and Proteins
- Progranulins
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Topics |
- Aged
- Analysis of Variance
- Aphasia, Primary Progressive
(genetics, metabolism, pathology)
- Brain
(metabolism, pathology)
- Cell Count
- DNA-Binding Proteins
(metabolism)
- Female
- Genetic Predisposition to Disease
- Humans
- Inclusion Bodies
(metabolism, pathology)
- Intercellular Signaling Peptides and Proteins
(genetics, metabolism)
- Mutation
(genetics)
- Neurofibrillary Tangles
(metabolism, pathology)
- Neurons
(metabolism, pathology)
- Pedigree
- Progranulins
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