Novel types of frontotemporal lobar degeneration: beyond tau and TDP-43

J Mol Neurosci. 2011 Nov;45(3):402-8. doi: 10.1007/s12031-011-9551-1. Epub 2011 May 21.


Most cases of frontotemporal lobar degeneration (FTLD) are characterized by the abnormal accumulation of either the microtubule-associated protein tau or the transactive response DNA-binding protein with M(r) 43 kDa, TDP-43 (FTLD-tau and FTLD-TDP, respectively). However, there remain ∼10% of cases, composed of a heterogenous collection of uncommon disorders, for which the molecular basis remains uncertain. In this review, we describe the characteristic genetic, clinical, and pathological features of the major tau/TDP-negative FTLD subtypes, with focus on recent advances in our understanding of their molecular basis. This includes the discovery that the pathological changes in atypical FTLD with ubiquitinated inclusions, neuronal intermediate filament inclusion disease, and basophilic inclusion body disease are immunoreactive for the fused in sarcoma (FUS) protein, resulting in the creation of a new molecular subgroup (FTLD-FUS), and studies clarifying the functional consequences of pathogenic CHMP2B mutations.

Publication types

  • Review

MeSH terms

  • Brain / metabolism
  • Brain / pathology
  • Chromosomes, Human, Pair 3
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Endosomal Sorting Complexes Required for Transport / genetics
  • Frontotemporal Lobar Degeneration / classification*
  • Frontotemporal Lobar Degeneration / genetics*
  • Frontotemporal Lobar Degeneration / pathology*
  • Frontotemporal Lobar Degeneration / physiopathology
  • Humans
  • Inclusion Bodies / chemistry
  • Inclusion Bodies / pathology
  • Intermediate Filaments / metabolism
  • Intermediate Filaments / pathology
  • Neurons / metabolism
  • Neurons / pathology
  • RNA-Binding Protein FUS / genetics
  • RNA-Binding Protein FUS / metabolism
  • Ubiquitin / metabolism
  • tau Proteins / genetics*
  • tau Proteins / metabolism


  • CHMP2B protein, human
  • DNA-Binding Proteins
  • Endosomal Sorting Complexes Required for Transport
  • RNA-Binding Protein FUS
  • Ubiquitin
  • tau Proteins