Association of plasma and cortical amyloid beta is modulated by APOE ε4 status

Shanker Swaminathan; Shannon L Risacher; Karmen K Yoder; John D West; Li Shen; Sungeun Kim; Mark Inlow; Tatiana Foroud; William J Jagust; Robert A Koeppe; Chester A Mathis; Leslie M Shaw; John Q Trojanowski; Holly Soares; Paul S Aisen; Ronald C Petersen; Michael W Weiner; Andrew J Saykin; Alzheimer's Disease Neuroimaging Initiative

doi:10.1016/j.jalz.2013.01.007

Association of plasma and cortical amyloid beta is modulated by APOE ε4 status

Alzheimers Dement. 2014 Jan;10(1):e9-e18. doi: 10.1016/j.jalz.2013.01.007. Epub 2013 Mar 26.

Authors

Shanker Swaminathan¹, Shannon L Risacher², Karmen K Yoder², John D West², Li Shen³, Sungeun Kim³, Mark Inlow⁴, Tatiana Foroud⁵, William J Jagust⁶, Robert A Koeppe⁷, Chester A Mathis⁸, Leslie M Shaw⁹, John Q Trojanowski⁹, Holly Soares¹⁰, Paul S Aisen¹¹, Ronald C Petersen¹², Michael W Weiner¹³, Andrew J Saykin¹⁴; Alzheimer's Disease Neuroimaging Initiative

Affiliations

¹ Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
² Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA.
³ Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA; Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN, USA.
⁴ Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Mathematics, Rose-Hulman Institute of Technology, Terre Haute, IN, USA.
⁵ Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA; Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN, USA.
⁶ Helen Wills Neuroscience Institute, University of California at Berkeley, Berkeley, CA, USA.
⁷ Division of Nuclear Medicine, Department of Radiology, University of Michigan, Ann Arbor, MI, USA.
⁸ Department of Radiology, University of Pittsburgh, Pittsburgh, PA, USA.
⁹ Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
¹⁰ Bristol Myers Squibb Co., Wallingford, CT, USA.
¹¹ Department of Neurosciences, University of California at San Diego, San Diego, CA, USA.
¹² Department of Neurology, Mayo Clinic and Foundation, Rochester, MN, USA.
¹³ Department of Veterans Affairs Medical Center, Center for Imaging of Neurodegenerative Diseases, San Francisco, CA, USA.
¹⁴ Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA; Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN, USA. Electronic address: asaykin@iupui.edu.

Abstract

Background: Apolipoprotein E (APOE) ε4 allele's role as a modulator of the relationship between soluble plasma amyloid beta (Aβ) and fibrillar brain Aβ measured by Pittsburgh compound B positron emission tomography ([(11)C]PiB PET) has not been assessed.

Methods: Ninety-six Alzheimer's Disease Neuroimaging Initiative participants with [(11)C]PiB scans and plasma Aβ1-40 and Aβ1-42 measurements at the time of PET scanning were included. Regional and voxelwise analyses of [(11)C]PiB data were used to determine the influence of APOE ε4 allele on association of plasma Aβ1-40, Aβ1-42, and Aβ1-40/Aβ1-42 with [(11)C]PiB uptake.

Results: In APOE ε4- but not ε4+ participants, positive relationships between plasma Aβ1-40/Aβ1-42 and [(11)C]PiB uptake were observed. Modeling the interaction of APOE and plasma Aβ1-40/Aβ1-42 improved the explained variance in [(11)C]PiB binding compared with using APOE and plasma Aβ1-40/Aβ1-42 as separate terms.

Conclusions: The results suggest that plasma Aβ is a potential Alzheimer's disease biomarker and highlight the importance of genetic variation in interpretation of plasma Aβ levels.

Keywords: Alzheimer's Disease Neuroimaging Initiative; Alzheimer's disease; Amyloid beta; Apolipoprotein E; Mild cognitive impairment; Pittsburgh compound B; Plasma amyloid beta; Positron emission tomography.

Publication types

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

MeSH terms

Aged
Aged, 80 and over
Alzheimer Disease* / genetics
Alzheimer Disease* / metabolism
Alzheimer Disease* / pathology
Amyloid beta-Peptides / metabolism*
Aniline Compounds
Apolipoproteins E / genetics
Brain / diagnostic imaging
Cerebral Cortex / metabolism*
Cognitive Dysfunction* / genetics
Cognitive Dysfunction* / metabolism
Cognitive Dysfunction* / pathology
Female
Humans
Male
Neuropsychological Tests
Peptide Fragments / metabolism*
Positron-Emission Tomography
Radiopharmaceuticals
Thiazoles

Substances

2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole
Amyloid beta-Peptides
Aniline Compounds
Apolipoproteins E
Peptide Fragments
Radiopharmaceuticals
Thiazoles
amyloid beta-protein (1-40)
amyloid beta-protein (1-42)

Abstract

Publication types

MeSH terms

Substances

Grants and funding