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Acta Neuropathologica

, Volume 116, Issue 1, pp 103–118 | Cite as

MAPT S305I mutation: implications for argyrophilic grain disease

  • Gabor G. Kovacs
  • Alan Pittman
  • Tamas ReveszEmail author
  • Connie Luk
  • Andrew Lees
  • Eva Kiss
  • Peter Tariska
  • Lajos Laszlo
  • Kinga Molnár
  • Maria J. Molnar
  • Markus Tolnay
  • Rohan de Silva
Case Report

Abstract

Frontotemporal lobar degeneration (FTLD) with mutations in the tau gene (MAPT) causes familial frontotemporal dementia with tau pathology. Many of these mutations result in morphological phenotypes resembling sporadic tauopathies, although, to date, no such cases mimicking argyrophilic grain disease (AgD) have been documented. We now present a case with a novel S305I MAPT mutation and a morphological phenotype showing resemblance to AgD. At the age of 39, the patient developed behavioural and personality changes and lack of verbal fluency with later poor performance on naming tasks and rigidity in the extremities. After a short disease course of 1.5 years, the patient died. A unique neuropathological phenotype with neuronal diffuse cytoplasmic tau immunoreactivity, oligodendroglial-coiled bodies, argyrophilic grains, and non-argyrophilic, but tau-immunopositive and ubiquitin-immunonegative pre-grains were observed, whereas classical neurofibrillary tangles, Pick bodies, and neuritic plaques were absent. The tau-positive abnormal structures were composed only of 4R-tau isoforms and, ultrastructurally, straight filaments. Neuronal loss was greatest in the medial temporal cortex, hippocampus, and amygdala. These pathological features resemble AgD. The novel S305I substitution has a strong effect on MAPT exon 10 splicing, thereby causing a striking increase in 4R-tau isoforms. Our observation not only widens the phenotypic spectrum of FTLD with MAPT mutation but also underpins the notion that the predominance of similar neuropathological findings in sporadic AgD cases may be viewed as features of a distinct disease entity.

Keywords

Tau Mutation Argyrophilic grain Frontotemporal lobar degeneration 

Notes

Acknowledgments

This work was supported by a grant from the Reta Lila Weston Trust for Medical Research (RdS, AP, CL, AJL), the PSP (Europe) Association (RdS, CL, AJL, TR), the Medical Research Council (RdS; Grant G0501560), the EU Grant FP6, BNEII No LSHM-CT-2004-503039 (GGK) and the Swiss National Science Foundation Grant 3100-068328 (MT), Alzheimer’s Research Trust (TR) and the Parkinson’s Disease Society (TR).

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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Gabor G. Kovacs
    • 1
    • 8
  • Alan Pittman
    • 2
  • Tamas Revesz
    • 3
    Email author
  • Connie Luk
    • 2
  • Andrew Lees
    • 2
  • Eva Kiss
    • 4
  • Peter Tariska
    • 4
  • Lajos Laszlo
    • 5
  • Kinga Molnár
    • 5
  • Maria J. Molnar
    • 6
  • Markus Tolnay
    • 7
  • Rohan de Silva
    • 2
  1. 1.Institute of NeurologyMedical University of ViennaViennaAustria
  2. 2.Reta Lila Weston Institute of Neurological Studies and Department of Molecular NeuroscienceUCL Institute of NeurologyLondonUK
  3. 3.Department of Molecular Neuroscience, Queen Square Brain BankUCL Institute of NeurologyLondonUK
  4. 4.National Insitute of Psychiatry and Neurology, Memory ClinicBudapestHungary
  5. 5.Department of Anatomy, Cell and Developmental BiologyEotvos Lorand University of SciencesBudapestHungary
  6. 6.Department of Molecular NeurologyNational Insitute of Psychiatry and NeurologyBudapestHungary
  7. 7.Institute of Pathology, Department of NeuropathologyUniversity Hospital BaselBaselSwitzerland
  8. 8.Department of NeuropathologyNational Insitute of Psychiatry and NeurologyBudapestHungary

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