Mapping the effects of ApoE4, age and cognitive status on 18F-florbetapir PET measured regional cortical patterns of beta-amyloid density and growth

Neuroimage. 2013 Sep;78:474-80. doi: 10.1016/j.neuroimage.2013.04.048. Epub 2013 Apr 23.


Background: Although it is well known that many clinical and genetic factors have been associated with beta-amyloid deposition, few studies have examined the interactions of such factors across different stages of Alzheimer's pathogenesis.

Methods: We used 18F-florbetapir F18 PET imaging to quantify neuritic beta-amyloid plaque density across four cortical regions in 602 elderly (55-94 years) subjects from the national ADNI biomarker study. The group comprised of 194 normal elderly, 212 early mild cognitive impairment [EMCI], 132 late mild cognitive impairment [LMCI], and 64 mild Alzheimer's (AD).

Findings: In a model incorporating multiple predictive factors, the effect of apolipoprotein E ε4 and diagnosis was significant on all four cortical regions. The highest signals were seen in cingulate followed by frontal and parietal with lowest signals in temporal lobe (p<0.0001). The effect of apolipoprotein E ε4 (Cohen's D 0.96) on beta-amyloid plaque density was approximately twice as large as the effect of a diagnosis of AD (Cohen's D 0.51) and thrice as large as the effect of a diagnosis of LMCI (Cohen's D 0.34) (p<0.0001). Surprisingly, ApoE ε4+ normal controls had greater mean plaque density across all cortical regions than ε4- EMCI and ε4- LMCI (p<0.0001, p=0.0009) and showed higher, though non-significant, mean value than ε4- AD patients (p<0.27). ApoE ε4+ EMCI and LMCI subjects had significantly greater mean plaque density across all cortical regions than ε4- AD patients (p<0.027, p<0.0001).

Interpretation: Neuritic amyloid plaque load across progressive clinical stages of AD varies strongly by ApoE4 genotype. These findings support the need for better pathology-based and supported diagnosis in routine practice. Our data also provides additional evidence for a temporal offset between amyloid deposition and clinically relevant symptoms.

Publication types

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

MeSH terms

  • Age Factors
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / genetics*
  • Alzheimer Disease / pathology
  • Amyloid / genetics
  • Amyloid / metabolism
  • Aniline Compounds
  • Apolipoprotein E4 / genetics*
  • Brain / diagnostic imaging*
  • Brain / pathology
  • Brain Mapping
  • Cognitive Dysfunction / genetics*
  • Cognitive Dysfunction / pathology
  • Ethylene Glycols
  • Female
  • Fluorine Radioisotopes
  • Humans
  • Male
  • Middle Aged
  • Plaque, Amyloid / genetics*
  • Plaque, Amyloid / pathology
  • Positron-Emission Tomography
  • Radiopharmaceuticals


  • Amyloid
  • Aniline Compounds
  • Apolipoprotein E4
  • Ethylene Glycols
  • Fluorine Radioisotopes
  • Radiopharmaceuticals
  • florbetapir