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

Shanker Swaminathan, Shannon L. Risacher, Karmen 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 Saykin

Research output: Contribution to journalArticle

23 Citations (Scopus)

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 ([11C]PiB PET) has not been assessed. Methods: Ninety-six Alzheimer's Disease Neuroimaging Initiative participants with [11C]PiB scans and plasma Aβ1-40 and Aβ1-42 measurements at the time of PET scanning were included. Regional and voxelwise analyses of [ 11C]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 [11C]PiB uptake. Results: In APOE ε4- but not ε4+ participants, positive relationships between plasma Aβ1-40/Aβ1-42 and [11C]PiB uptake were observed. Modeling the interaction of APOE and plasma Aβ1-40/Aβ1-42 improved the explained variance in [11C]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.

Original languageEnglish
JournalAlzheimer's and Dementia
Volume10
Issue number1
DOIs
StatePublished - Jan 2014

Fingerprint

Apolipoprotein E4
Amyloid
Apolipoproteins E
Alzheimer Disease
Alleles
Neuroimaging
Positron-Emission Tomography
Biomarkers
Brain

Keywords

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

ASJC Scopus subject areas

  • Health Policy
  • Epidemiology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Developmental Neuroscience
  • Clinical Neurology

Cite this

Association of plasma and cortical amyloid beta is modulated by APOE ε4 status. / Swaminathan, Shanker; Risacher, Shannon L.; Yoder, Karmen; West, John D.; Shen, Li; Kim, Sungeun; Inlow, Mark; Foroud, Tatiana; Jagust, William J.; Koeppe, Robert A.; Mathis, Chester A.; Shaw, Leslie M.; Trojanowski, John Q.; Soares, Holly; Aisen, Paul S.; Petersen, Ronald C.; Weiner, Michael W.; Saykin, Andrew.

In: Alzheimer's and Dementia, Vol. 10, No. 1, 01.2014.

Research output: Contribution to journalArticle

Swaminathan, S, Risacher, SL, Yoder, K, West, JD, Shen, L, Kim, S, Inlow, M, Foroud, T, Jagust, WJ, Koeppe, RA, Mathis, CA, Shaw, LM, Trojanowski, JQ, Soares, H, Aisen, PS, Petersen, RC, Weiner, MW & Saykin, A 2014, 'Association of plasma and cortical amyloid beta is modulated by APOE ε4 status', Alzheimer's and Dementia, vol. 10, no. 1. https://doi.org/10.1016/j.jalz.2013.01.007
Swaminathan, Shanker ; Risacher, Shannon L. ; Yoder, Karmen ; West, John D. ; Shen, Li ; Kim, Sungeun ; Inlow, Mark ; Foroud, Tatiana ; Jagust, William J. ; Koeppe, Robert A. ; Mathis, Chester A. ; Shaw, Leslie M. ; Trojanowski, John Q. ; Soares, Holly ; Aisen, Paul S. ; Petersen, Ronald C. ; Weiner, Michael W. ; Saykin, Andrew. / Association of plasma and cortical amyloid beta is modulated by APOE ε4 status. In: Alzheimer's and Dementia. 2014 ; Vol. 10, No. 1.
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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 ([11C]PiB PET) has not been assessed. Methods: Ninety-six Alzheimer's Disease Neuroimaging Initiative participants with [11C]PiB scans and plasma Aβ1-40 and Aβ1-42 measurements at the time of PET scanning were included. Regional and voxelwise analyses of [ 11C]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 [11C]PiB uptake. Results: In APOE ε4- but not ε4+ participants, positive relationships between plasma Aβ1-40/Aβ1-42 and [11C]PiB uptake were observed. Modeling the interaction of APOE and plasma Aβ1-40/Aβ1-42 improved the explained variance in [11C]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.",
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AU - Swaminathan, Shanker

AU - Risacher, Shannon L.

AU - Yoder, Karmen

AU - West, John D.

AU - Shen, Li

AU - Kim, Sungeun

AU - Inlow, Mark

AU - Foroud, Tatiana

AU - Jagust, William J.

AU - Koeppe, Robert A.

AU - Mathis, Chester A.

AU - Shaw, Leslie M.

AU - Trojanowski, John Q.

AU - Soares, Holly

AU - Aisen, Paul S.

AU - Petersen, Ronald C.

AU - Weiner, Michael W.

AU - Saykin, Andrew

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N2 - 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 ([11C]PiB PET) has not been assessed. Methods: Ninety-six Alzheimer's Disease Neuroimaging Initiative participants with [11C]PiB scans and plasma Aβ1-40 and Aβ1-42 measurements at the time of PET scanning were included. Regional and voxelwise analyses of [ 11C]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 [11C]PiB uptake. Results: In APOE ε4- but not ε4+ participants, positive relationships between plasma Aβ1-40/Aβ1-42 and [11C]PiB uptake were observed. Modeling the interaction of APOE and plasma Aβ1-40/Aβ1-42 improved the explained variance in [11C]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.

AB - 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 ([11C]PiB PET) has not been assessed. Methods: Ninety-six Alzheimer's Disease Neuroimaging Initiative participants with [11C]PiB scans and plasma Aβ1-40 and Aβ1-42 measurements at the time of PET scanning were included. Regional and voxelwise analyses of [ 11C]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 [11C]PiB uptake. Results: In APOE ε4- but not ε4+ participants, positive relationships between plasma Aβ1-40/Aβ1-42 and [11C]PiB uptake were observed. Modeling the interaction of APOE and plasma Aβ1-40/Aβ1-42 improved the explained variance in [11C]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.

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