Acta Neuropathologica

, Volume 120, Issue 1, pp 43–54

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

  • Eileen H. Bigio
  • Manjari Mishra
  • Kimmo J. Hatanpaa
  • Charles L. WhiteIII
  • Nancy Johnson
  • Alfred Rademaker
  • Bing Bing Weitner
  • Han-Xiang Deng
  • Steven D. Dubner
  • Sandra Weintraub
  • Marsel Mesulam
Original Paper

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.

Keywords

Primary progressive aphasia Frontotemporal dementia Alzheimer disease FTLD-TDP TDP-43 proteinopathy Hippocampal sclerosis 

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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Eileen H. Bigio
    • 1
    • 2
  • Manjari Mishra
    • 1
  • Kimmo J. Hatanpaa
    • 3
  • Charles L. WhiteIII
    • 3
  • Nancy Johnson
    • 1
    • 4
  • Alfred Rademaker
    • 1
    • 5
  • Bing Bing Weitner
    • 5
  • Han-Xiang Deng
    • 4
  • Steven D. Dubner
    • 1
    • 2
  • Sandra Weintraub
    • 1
    • 6
  • Marsel Mesulam
    • 1
    • 4
  1. 1.Cognitive Neurology and Alzheimer Disease CenterNorthwestern University Feinberg School of MedicineChicagoUSA
  2. 2.Department of PathologyNorthwestern University Feinberg School of MedicineChicagoUSA
  3. 3.Department of PathologyAlzheimer Disease Center, University of Texas Southwestern Medical CenterDallasUSA
  4. 4.Department of NeurologyNorthwestern University Feinberg School of MedicineChicagoUSA
  5. 5.Department of Preventive MedicineNorthwestern University Feinberg School of MedicineChicagoUSA
  6. 6.Department of PsychiatryNorthwestern University Feinberg School of MedicineChicagoUSA

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