Clinicopathological study of diffuse neurofibrillary tangles with calcification. With special reference to TDP-43 proteinopathy and alpha-synucleinopathy.

Abstract

Diffuse neurofibrillary tangles with calcification (DNTC) is a relatively rare presenile dementia that clinically shows overlapping symptoms of Alzheimer's disease and frontotemporal lobar degeneration (FTLD). DNTC is pathologically characterized by localized temporal or frontotemporal atrophy with massive neurofibrillary tangles, neuropil threads and Fahr's-type calcification without senile plaques. We tried to clarify the molecular basis of DNTC by immunohistochemically examining the appearance and distribution of accumulated alpha-synuclein (aSyn) and TAR DNA-binding protein of 43kDa (TDP-43) in the brains of 10 Japanese autopsy cases. We also investigated the clinically characteristic symptoms from the clinical charts and previous reports, and the correlations with neuropathological findings. The characteristic symptoms were evaluated using the Neuropsychiatric Inventory Questionnaire (NPI-Q). As a result, we confirmed the high frequency of neuronal cytoplasmic accumulation of aSyn (80%) and phosphorylated TDP-43 (90%) in DNTC cases. There was a significant correlation between some selected items of NPI-Q scores and the severity of the limbic TDP-43 pathology. The pathology of DNTC included TDP-43 and aSyn pathology with high frequency. These abnormal accumulations of TDP-43 might be involved in the pathological process of DNTC, having a close relationship to the FTLD-like psychiatric symptoms during the clinical course.

• Authors: Chikako Habuchi, Shuji Iritani, Hirotaka Sekiguchi, Youta Torii, Ryoko Ishihara, Tetsuaki Arai, Masato Hasegawa, Kuniaki Tsuchiya, Haruhiko Akiyama, Hiroto Shibayama, Norio Ozaki
• Journal: Journal of the neurological sciences (J Neurol Sci) Vol. 301 Issue 1-2 Pg. 77-85 (Feb 15 2011) ISSN: 1878-5883 [Electronic] Netherlands
• PMID: 21106208 (Publication Type: Journal Article)
• Copyright: Copyright © 2010 Elsevier B.V. All rights reserved.

Chemical References

• DNA-Binding Proteins
• alpha-Synuclein

Topics

• Aged
• Brain Chemistry
• Cytoplasm (chemistry)
• DNA-Binding Proteins (analysis)
• Diffuse Neurofibrillary Tangles with Calcification (diagnosis, metabolism, pathology, psychology)
• Female
• Humans
• Lewy Bodies (chemistry, ultrastructure)
• Male
• Memory Disorders (etiology)
• Mental Disorders (etiology)
• Middle Aged
• Neurites (chemistry, ultrastructure)
• Neurofibrillary Tangles (chemistry, ultrastructure)
• Neuropsychological Tests
• Personality Disorders (etiology)
• Phosphorylation
• Protein Processing, Post-Translational
• Surveys and Questionnaires
• TDP-43 Proteinopathies (metabolism, pathology, psychology)
• alpha-Synuclein (analysis)