Skip to main content
Article thumbnail
Location of Repository

Heterogeneity of ubiquitin pathology in frontotemporal lobar degeneration: classification and relation to clinical phenotype

By Ian R. A. Mackenzie, Atik Baborie, Stuart Pickering-Brown, Daniel Du Plessis, Evelyn Jaros, Robert H. Perry, David Neary, Julie S. Snowden and David M. A. Mann


We have investigated the extent and pattern of immunostaining for ubiquitin protein (UBQ) in 60 patients with frontotemporal lobar degeneration (FTLD) with ubiquitin-positive, tau-negative inclusions (FTLD-U), 37 of whom were ascertained in Manchester UK and 23 in Newcastle-Upon-Tyne, UK. There were three distinct histological patterns according to the form and distribution of the UBQ pathology. Histological type 1 was present in 19 patients (32%) and characterised by the presence of a moderate number, or numerous, UBQ immunoreactive neurites and intraneuronal cytoplasmic inclusions within layer II of the frontal and temporal cerebral cortex, and cytoplasmic inclusions within granule cells of the dentate gyrus; neuronal intranuclear inclusions (NII) of a “cat’s eye” or “lentiform” appearance were present in 17 of these patients. In histological type 2 (16 patients, 27%), UBQ neurites were predominantly, or exclusively, present with few intraneuronal cytoplasmic inclusions within layer II of the cerebral cortex, while in histological type 3 (25 patients, 42%), UBQ intraneuronal cytoplasmic inclusions either within the cortical layer II or in the granule cells of the dentate gyrus, with few or no UBQ neurites, were seen. In neither of these latter two groups were NII present. The influence of histological type on clinical phenotype was highly significant with type 1 histology being associated clinically with cases of frontotemporal dementia (FTD) or progressive non-fluent aphasia (PNFA), type 2 histology with semantic dementia (SD), and type 3 histology with FTD, or FTD and motor neurone disease (MND)

Topics: Original Paper
Publisher: Springer-Verlag
OAI identifier:
Provided by: PubMed Central

Suggested articles


  1. (2006). A family with tau-negative dementia and neuronal intranuclear inclusions linked to chromosome 17.
  2. (1994). Clinical, neuropsychological and neuropathological criteria for fronto-temporal dementia.
  3. (2006). Clinicopathologic analysis of frontotemporal and corticobasal degenerations and PSP.
  4. (2004). Clinicopathological correlates in frontotemporal dementia.
  5. (2004). Cortical ubiquitin-positive inclusions in frontotemporal dementia without motor neurone disease: a quantitative immunocytochemical study.
  6. (2006). dementia lacking distinctive histology (DLDH) revisited. Acta Neuropathol
  7. (1996). DiVerent variants of frontotemporal dementia: a neuropathological and immunohistochemical study.
  8. (2003). Extended investigation of tau and mutation screening of other candidate genes on chromosome 17q21 in a Swedish FTDP-17 family.
  9. (2001). Familial frontotemporal dementia with ubiquitin positive inclusions is linked to chromosome 17q21–22.
  10. (1990). Frontal lobe dementia and motor neurone disease.
  11. (1996). Fronto-temporal lobar degeneration: fronto-temporal dementia, progressive aphasia, semantic dementia.
  12. (2001). Frontotemporal dementia with ubiquitinated cytoplasmic and intranuclear inclusions.
  13. (2006). Frontotemporal dementia: clinicopathological correlations.
  14. (2005). Frontotemporal dementia.
  15. (2004). Frontotemporal lobar degeneration and ubiquitin immunohistochemistry.
  16. (2004). Frontotemporal lobar degeneration with motor neuron disease-type inclusions predominates in 76 cases of frontotemporal degeneration.
  17. (1998). Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria.
  18. (1992). Hippocampal and neocortical ubiquitin-immunoreactive inclusions in amyotrophic lateral sclerosis with dementia.
  19. (2005). Histopathological changes underlying frontotemporal lobar degeneration with clinicopathological correlation.
  20. (2005). Mutant valosin-containing protein causes a novel type of frontotemporal dementia. Ann Neurol 57:457–461Acta Neuropathol
  21. (2006). Mutations in Progranulin cause tau-negative frontotemporal dementia linked to chromosome 17.
  22. (2004). Neuronal ubiquitinated intranuclear inclusions in familial and non-familial frontotemporal dementia of the motor neurone disease type associated with amyotrophic lateral sclerosis.
  23. (2005). Neuropathologic, biochemical, and molecular characterization of the frontotemporal dementias.
  24. (2006). Novel ubiquitin pathology in frontotemporal dementia with valosin-containig protein gene mutations.
  25. (2006). Null mutations in progranulin cause ubiquitin-positive frontotemporal dementia linked to chromosome 17q21.
  26. (2000). Semantic dementia with ubiquitin-positive tau-negative inclusion bodies.
  27. (2003). Survival in frontotemporal dementia.
  28. (2002). Tau-negative frontal lobe dementia at 17q21: signiWcant Wnemapping of the candidate region to a 4.8-cm interval.
  29. (2005). The genetics and molecular pathology of frontotemporal lobar degeneration. In: Burns A, O’Brien J, Ames D (eds) Dementia, 3rd edn. Hodder Arnold, London,
  30. (2004). The neuropathology of frontotemporal lobar degeneration with respect to the cytological and biochemical characteristics of tau protein.
  31. (2003). The relationship between extramotor ubiquitin-immunoreactive neuronal inclusions and dementia in motor neurone disease.
  32. (2005). Ubiquitin immunohistochemistry of frontotemporal lobar degeneration diVerentiates cases with and without motor neurone disease. Alzheimer Dis Assoc Disord 19(suppl 1):S37–S43

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.