Journal of Neural Transmission

, Volume 122, Issue 7, pp 1007–1018

Frontotemporal lobar degeneration FTLD-tau: preclinical lesions, vascular, and Alzheimer-related co-pathologies

  • Dietmar Rudolf Thal
  • Christine A. F. von Arnim
  • W. Sue T. Griffin
  • Robert E. Mrak
  • Lauren Walker
  • Johannes Attems
  • Thomas Arzberger
Neurology and Preclinical Neurological Studies - Original Article

DOI: 10.1007/s00702-014-1360-6

Cite this article as:
Thal, D.R., von Arnim, C.A.F., Griffin, W.S.T. et al. J Neural Transm (2015) 122: 1007. doi:10.1007/s00702-014-1360-6

Abstract

Frontotemporal lobar degeneration with τ pathology (FTLD-tau) is one of a group of neurodegenerative diseases that manifests with cognitive decline. Alzheimer (AD) and cerebrovascular lesions are commonly noted in the brains of most elderly individuals, begging the question as to whether (a) coexisting AD and vascular pathology or age contribute to the development of FTLD-tau disorders and vice versa and (b) FTLD-tau-like pathology can be found in non-diseased individuals. We studied brains of FTLD-tau cases exhibiting (a) argyrophilc grain disease (AGD), (b) progressive supranuclear palsy (PSP), (c) corticobasal degeneration (CBD), or (d) Pick’s disease (PiD) for coexisting AD and vascular pathology for comparison with that of non-diseased individuals and AD patients. We confirmed that AGD lowered the threshold for AD pathology to cause dementia. Such an effect was not seen in PSP, CBD, or PiD. In PiD, white matter degeneration and demyelination was observed in the frontal and temporal lobes in association with small vessel disease (SVD)-related changes in white matter arteries. Age at death varied among the four types of FTLD-tau. PiD cases were youngest at death followed by CBD, PSP, and finally AGD. In 9.8 % of non-diseased controls, we found grains, coiled bodies, and/or τ-positive astrocytes mimicking an AGD-like pattern. Moreover, the prevalence of FTLD-tau pathology in non-diseased individuals increased with age. In summary, this study demonstrates that age impacts of the diversity of neuropathological changes in FTLD-tau. The age-related coexistence of AD-related pathology is, thereby, associated with AGD but not with PSP, CBD, and PiD. Moreover, severe SVD and white matter demyelination is associated with PiD indicating a role of vascular copathology in this type of FTLD-tau. Finally, our finding that FTLD-tau-related pathological lesions occur in non-diseased individuals suggests that preclinical stages of FTLD-tau exist. As such, our results indicate that age, together with vascular and AD-related copathology, contributes to the morphological appearance of FTLD-tau.

Keywords

FTLD-tau Alzheimer’s disease Vascular pathology Preclinical stages Tau Age 

Supplementary material

702_2014_1360_MOESM1_ESM.doc (32 kb)
Supplementary material 1 (DOC 31 kb)

Copyright information

© Springer-Verlag Wien 2015

Authors and Affiliations

  • Dietmar Rudolf Thal
    • 1
  • Christine A. F. von Arnim
    • 2
  • W. Sue T. Griffin
    • 3
    • 4
  • Robert E. Mrak
    • 5
  • Lauren Walker
    • 6
  • Johannes Attems
    • 6
  • Thomas Arzberger
    • 7
    • 8
  1. 1.Laboratory of Neuropathology, Institute of Pathology, Center for Clinical ResearchUlm UniversityUlmGermany
  2. 2.Department of NeurologyUlm UniversityUlmGermany
  3. 3.Donald W. Reynolds Center on AgingUniversity of Arkansas for Medical Sciences (UAMS)Little RockUSA
  4. 4.Geriatric Research Education and Clinical CenterVeteran’s Affairs Medical CenterLittle RockUSA
  5. 5.Department of PathologyUniversity of ToledoToledoUSA
  6. 6.Institute for Ageing and HealthNewcastle UniversityNewcastle upon TyneUK
  7. 7.Centre for Neuropathology and Prion ResearchLudwig-Maximilians-University MunichMunichGermany
  8. 8.Department of Psychiatry and PsychotherapyLudwig-Maximilians-University MunichMunichGermany

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