Differential effect of APOE genotype on amyloid load and glucose metabolism in AD dementia

Neurology. 2013 Jan 22;80(4):359-65. doi: 10.1212/WNL.0b013e31827f0889. Epub 2012 Dec 19.

Abstract

Objective: To examine the relationships between apolipoprotein E (APOE) ε4 dose and in vivo distributions of both fibrillary amyloid burden and glucose metabolism in the same Alzheimer disease dementia patients, selected for abnormal amyloid imaging.

Methods: Twenty-two APOE ε4 negative, 40 heterozygous, and 22 homozygous Alzheimer disease dementia patients underwent dynamic (90 minutes) [(11)C]Pittsburgh compound B (PIB) and static [(18)F]fluorodeoxyglucose (FDG) PET scans. Parametric nondisplaceable binding potential images of [(11)C]PIB and standardized uptake value ratio images of [(18)F]FDG were generated using cerebellar gray matter as reference tissue. Frontal, parietal, temporal, posterior cingulate, and occipital cortices were selected as regions of interest.

Results: Multivariate general linear models with adjustment for age, sex, and Mini-Mental State Examination showed main effects of APOE ε4 dose on distributions of both [(11)C]PIB (p for trend <0.05) and [(18)F]FDG (p for trend <0.01). More specifically, a univariate general linear model of individual regions showed increased [(11)C]PIB binding in frontal cortex of APOE ε4 noncarriers compared with APOE ε4 carriers (p < 0.05). In contrast, APOE ε4 carriers had reduced [(18)F]FDG uptake in occipital cortex (p < 0.05) and a borderline significant effect in posterior cingulate (p = 0.07) in a dose-dependent manner.

Conclusion: We found a reversed APOE ε4 dose effect for amyloid deposition in the frontal lobe, whereas APOE ε4 carriership was associated with more profound metabolic impairment in posterior parts of the cortex. These findings suggest that APOE genotype has a differential effect on the distribution of amyloid plaques and glucose metabolism. This may have important implications for emerging therapies that aim to directly intervene in the disease process.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / diagnostic imaging
  • Alzheimer Disease / genetics*
  • Alzheimer Disease / metabolism*
  • Amyloidosis / diagnostic imaging
  • Amyloidosis / genetics*
  • Amyloidosis / metabolism*
  • Aniline Compounds
  • Apolipoproteins E / genetics*
  • Benzothiazoles
  • Blood Glucose / metabolism*
  • Cerebral Cortex / diagnostic imaging
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / pathology
  • Female
  • Fluorodeoxyglucose F18
  • Genotype
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Positron-Emission Tomography / methods
  • Severity of Illness Index
  • Thiazoles

Substances

  • 2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole
  • Aniline Compounds
  • Apolipoproteins E
  • Benzothiazoles
  • Blood Glucose
  • Thiazoles
  • Fluorodeoxyglucose F18