Voxel-based morphometry in frontotemporal lobar degeneration with ubiquitin-positive inclusions with and without progranulin mutations

Arch Neurol. 2007 Mar;64(3):371-6. doi: 10.1001/archneur.64.3.371.

Abstract

Background: Mutations in the progranulin gene (PGRN) have recently been identified as a cause of frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U) in some families.

Objective: To determine whether there is a difference in the patterns of atrophy in FTLD-U cases with and without PGRN mutations.

Design: Case-control study.

Setting: Brain bank of a tertiary care medical center. Patients Eight subjects who had screened positive for PGRN mutations (PGRN-positive) and who underwent volumetric magnetic resonance imaging were identified. Subjects were then matched by clinical diagnosis to a group of 8 subjects with a pathological diagnosis of FTLD-U who had screened negative for PGRN mutations (PGRN-negative). All subjects were then age-matched and sex-matched to a control subject.

Main outcome measures: Voxel-based morphometry was used to assess the patterns of gray matter atrophy in the PGRN-positive group compared with the PGRN-negative group and compared with controls.

Results: The PGRN-positive group showed a widespread and severe pattern of gray matter loss predominantly affecting the frontal, temporal, and parietal lobes. The PGRN-negative group showed a less severe pattern of gray matter loss restricted mainly to the temporal and frontal lobes. On direct comparison, the PGRN-positive group showed greater gray matter loss in the frontal and parietal lobes compared with the PGRN-negative group.

Conclusion: Findings from this study suggest that PGRN mutations may be associated with a specific and severe pattern of cerebral atrophy in subjects with FTLD-U.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Brain Mapping
  • Case-Control Studies
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / pathology*
  • Dementia* / genetics
  • Dementia* / metabolism
  • Dementia* / pathology
  • Female
  • Humans
  • Inclusion Bodies / metabolism*
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Magnetic Resonance Imaging / methods
  • Male
  • Middle Aged
  • Mutation*
  • Progranulins
  • Ubiquitin / metabolism*

Substances

  • GRN protein, human
  • Intercellular Signaling Peptides and Proteins
  • Progranulins
  • Ubiquitin