Functional correlates of Apolipoprotein E genotype in Frontotemporal Lobar Degeneration

BMC Neurol. 2006 Aug 24:6:31. doi: 10.1186/1471-2377-6-31.

Abstract

Background: It has been recently demonstrated that in Frontotemporal Lobar Degeneration (FTLD) memory deficits at presentation are commoner than previously thought. Apolipoprotein E (ApoE) genotype, the major genetic risk factor in sporadic late-onset Alzheimer Disease (AD), modulates cerebral perfusion in late middle-age cognitively normal subjects. ApoE epsilon4 homozygous have reduced glucose metabolism in the same regions involved in AD. The aim of this study was to determine whether ApoE genotype might play a key-role in influencing the cerebral functional pattern as well as the degree of memory deficits in FTLD patients.

Methods: Fifty-two unrelated FTLD patients entered the study and underwent a somatic and neurological evaluation, laboratory examinations, a brain structural imaging study, and a brain functional Single Photon Emission Tomography study. ApoE genotype was determined.

Results: ApoE genotype influenced both clinical and functional features in FTLD. ApoE epsilon4-carriers were more impaired in long-term memory function (ApoE epsilon4 vs. ApoE non epsilon4, 6.3 +/- 3.9 vs. 10.1 +/- 4.2, p = 0.004) and more hypoperfused in uncus and parahippocampal regions (x,y,z = 38,-6,-20, T = 2.82, cluster size = 100 voxels; -32,-12,-28, T= 2.77, cluster size = 40 voxels).

Conclusion: The present findings support the view that ApoE genotype might be considered a disease-modifying factor in FTLD, thus contributing to define a specific clinical presentation, and might be of relevance for pharmacological approaches.

MeSH terms

  • Adult
  • Aged
  • Apolipoproteins E / genetics*
  • Brain Ischemia / etiology*
  • Cross-Sectional Studies
  • Dementia / complications*
  • Dementia / genetics
  • Dementia / psychology*
  • Genotype
  • Heterozygote
  • Humans
  • Memory*
  • Middle Aged
  • Parahippocampal Gyrus / blood supply*

Substances

  • Apolipoproteins E