Correlation between Apolipoprotein E genotype and brain metabolism in amyotrophic lateral sclerosis

Eur J Neurol. 2019 Feb;26(2):306-312. doi: 10.1111/ene.13812. Epub 2018 Oct 24.


Background and purpose: The aim of the study was to evaluate the metabolic correlates of Apolipoprotein E (APOE) genotype in amyotrophic lateral sclerosis (ALS) and to investigate the role of ε2 as a risk factor for cognitive impairment.

Methods: A total of 159 ALS cases underwent APOE and ALS-related genes analysis, neuropsychological assessment and cerebral 18 F-2-fluoro-2-deoxy-D-glucose positron emission tomography. The APOE genotype was regressed against whole brain metabolism as assessed by 18 F-2-fluoro-2-deoxy-D-glucose positron emission tomography, with age, sex, education, type of onset and C9orf72 status as covariates.

Results: Brain metabolism was significantly positively correlated with APOE genotype from ε2/ε2 to ε3/ε4 in the left prefrontal [Brodmann area (BA) 10], orbitofrontal (BAs 11, 45, 47) and anterior cingulate (BA 32) cortices. There was a tendency to a relative hypometabolism going towards the ε2/ε2 extreme.

Conclusions: We found a highly significant, relatively lower metabolism in association with the ε2 allele in extra-motor areas typically affected in frontotemporal dementia (left prefrontal, orbitofrontal and anterior cingulate cortices), strengthening the finding of a role of ε2 as a risk factor for cognitive impairment in ALS. Our data suggested a link between cholesterol homeostasis and neurodegeneration.

Keywords: Apolipoprotein E; 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography; amyotrophic lateral sclerosis; frontotemporal dementia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alleles
  • Amyotrophic Lateral Sclerosis / diagnostic imaging
  • Amyotrophic Lateral Sclerosis / genetics*
  • Amyotrophic Lateral Sclerosis / metabolism
  • Apolipoproteins E / genetics*
  • Brain / diagnostic imaging
  • Brain / metabolism*
  • Female
  • Genotype*
  • Glucose / metabolism
  • Humans
  • Male
  • Middle Aged
  • Positron-Emission Tomography
  • Risk Factors


  • Apolipoproteins E
  • Glucose