4.5 Article

A Multi-Cohort Study of ApoE ε4 and Amyloid-β Effects on the Hippocampus in Alzheimer's Disease

Journal

JOURNAL OF ALZHEIMERS DISEASE
Volume 56, Issue 3, Pages 1159-1174

Publisher

IOS PRESS
DOI: 10.3233/JAD-161097

Keywords

Alzheimer's disease; amyloid; APOE epsilon 4; hippocampus; magnetic resonance imaging; mild cognitive impairment

Categories

Funding

  1. InnoMed, (Innovative Medicines in Europe) an Integrated Project - European Union of the Sixth Framework program [FP6-2004-LIFESCIHEALTH-5]
  2. Life Sciences, Genomics and Biotechnology for Health, Health Research Council of Academy of Finland
  3. Gamla Tjanarinnor Foundation
  4. Swedish Alzheimer's Association
  5. Swedish Brain Power
  6. Stiftelsen for Gamla Tjanarinnor
  7. Sigurd och Elsa Goljes Minne
  8. Swedish Research Council
  9. Swedish Council for Working Life and Social Research
  10. Swedish Brain Power, an Alexander von Humboldt Research Award
  11. IMAGEN project
  12. European Community's Sixth Framework Program [LSHM-CT-2007-037286]
  13. coordinated project ADAMS [242257]
  14. NIHR Biomedical Research Centre for Mental Health
  15. NIHR Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation Trust
  16. Institute of Psychiatry, Psychology, and Neuroscience (IoPPN), King's College London
  17. Alzheimer Research UK
  18. IMI
  19. InnoMed, (Innovative Medicines in Europe) an Integrated Project - European Union of the Sixth Framework program [FP6-2004-LIFESCIHEALTH-5]
  20. Life Sciences, Genomics and Biotechnology for Health, Health Research Council of Academy of Finland
  21. Gamla Tjanarinnor Foundation
  22. Swedish Alzheimer's Association
  23. Swedish Brain Power
  24. Stiftelsen for Gamla Tjanarinnor
  25. Sigurd och Elsa Goljes Minne
  26. Swedish Research Council
  27. Swedish Council for Working Life and Social Research
  28. Swedish Brain Power, an Alexander von Humboldt Research Award
  29. IMAGEN project
  30. European Community's Sixth Framework Program [LSHM-CT-2007-037286]
  31. coordinated project ADAMS [242257]
  32. NIHR Biomedical Research Centre for Mental Health
  33. NIHR Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation Trust
  34. Institute of Psychiatry, Psychology, and Neuroscience (IoPPN), King's College London
  35. Alzheimer Research UK
  36. IMI
  37. Medical Research Council [MR/N026063/1] Funding Source: researchfish
  38. Parkinson's UK [J-1403] Funding Source: researchfish
  39. MRC [MR/N026063/1] Funding Source: UKRI

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The apolipoprotein E (APOE) gene has been consistently shown to modulate the risk of Alzheimer's disease (AD). Here, using an AD and normal aging dataset primarily consisting of three AD multi-center studies (n = 1,781), we compared the effect of APOE and amyloid-beta (A beta) on baseline hippocampal volumes in AD patients, mild cognitive impairment (MCI) subjects, and healthy controls. A large sample of healthy adolescents (n = 1,387) was also used to compare hippocampal volumes between APOE groups. Subjects had undergone a magnetic resonance imaging (MRI) scan and APOE genotyping. Hippocampal volumes were processed using FreeSurfer. In the AD and normal aging dataset, hippocampal comparisons were performed in each APOE group and in epsilon 4 carriers with positron emission tomography (PET) A beta who were dichotomized (A beta+/A beta-) using previous cut-offs. We found a linear reduction in hippocampal volumes with epsilon 4 carriers possessing the smallest volumes, epsilon 3 carriers possessing intermediate volumes, and epsilon 2 carriers possessing the largest volumes. Moreover, AD and MCI epsilon 4 carriers possessed the smallest hippocampal volumes and control epsilon 2 carriers possessed the largest hippocampal volumes. Subjects with both APOE epsilon 4 and A beta positivity had the lowest hippocampal volumes when compared to A beta-epsilon 4 carriers, suggesting a synergistic relationship between APOE epsilon 4 and A beta. However, we found no hippocampal volume differences between APOE groups in healthy 14-year-old adolescents. Our findings suggest that the strongest neuroanatomic effect of APOE epsilon 4 on the hippocampus is observed in AD and groups most at risk of developing the disease, whereas hippocampi of old and young healthy individuals remain unaffected.

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