Amyloid beta peptides in human plasma and tissues and their significance for Alzheimer's disease

Alex E. Roher, Chera L. Esh, Tyler A. Kokjohn, Eduardo M. Castaño, Gregory D. Van Vickle, Walter M. Kalback, R. Lyle Patton, Dean C. Luehrs, Ian D. Daugs, Yu Min Kuo, Mark R. Emmerling, Holly Soares, Joseph F. Quinn, Jeffrey Kaye, Donald J. Connor, Nina B. Silverberg, Charles Howard Adler, James D. Seward, Thomas G. Beach, Marwan N. Sabbagh

Research output: Contribution to journalArticle

179 Citations (Scopus)

Abstract

Background: We evaluated the amounts of amyloid beta (Aβ)) peptides in the central nervous system (CNS) and in reservoirs outside the CNS and their potential impact on Aβ plasma levels and Alzheimer's disease (AD) pathology. Methods: Amyloid β levels were measured in (1) the plasma of AD and nondemented (ND) controls in a longitudinal study, (2) the plasma of a cohort of AD patients receiving a cholinesterase inhibitor, and (3) the skeletal muscle, liver, aorta, platelets, leptomeningeal arteries, and in gray and white matter of AD and ND control subjects. Results: Plasma Aβ levels fluctuated over time and among individuals, suggesting continuous contributions from brain and peripheral tissues and associations with reactive circulating proteins. Arteries with atherosclerosis had larger amounts of Aβ40 than disease-free vessels. Inactivated platelets contained more Aβ peptides than activated ones. Substantially more Aβ was present in liver samples from ND patients. Overall, AD brain and skeletal muscle contained increased levels of Aβ. Conclusions: Efforts to use plasma levels of Aβ peptides as AD biomarkers or disease-staging scales have failed. Peripheral tissues might contribute to both the circulating amyloid pool and AD pathology within the brain and its vasculature. The wide spread of plasma Aβ values is also due in part to the ability of Aβ to bind to a variety of plasma and membrane proteins. Sources outside the CNS must be accounted for because pharmacologic interventions to reduce cerebral amyloid are assessed by monitoring Aβ plasma levels. Furthermore, the long-range impact of Aβ immunotherapy on peripheral Aβ sources should also be considered.

Original languageEnglish (US)
Pages (from-to)18-29
Number of pages12
JournalAlzheimer's and Dementia
Volume5
Issue number1
DOIs
StatePublished - Jan 2009

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Amyloid beta-Peptides
Alzheimer Disease
Amyloid
Central Nervous System
Brain
Skeletal Muscle
Blood Platelets
Arteries
Pathology
Leukoencephalopathies
Peptides
Aptitude
Liver
Cholinesterase Inhibitors
Immunotherapy
Longitudinal Studies
Aorta
Blood Proteins
Atherosclerosis
Membrane Proteins

Keywords

  • Aβ immunotherapy
  • Alzheimer's disease
  • Atherosclerotic vascular disease
  • Peripheral Aβ
  • Plasma Aβ

ASJC Scopus subject areas

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

Cite this

Roher, A. E., Esh, C. L., Kokjohn, T. A., Castaño, E. M., Van Vickle, G. D., Kalback, W. M., ... Sabbagh, M. N. (2009). Amyloid beta peptides in human plasma and tissues and their significance for Alzheimer's disease. Alzheimer's and Dementia, 5(1), 18-29. https://doi.org/10.1016/j.jalz.2008.10.004

Amyloid beta peptides in human plasma and tissues and their significance for Alzheimer's disease. / Roher, Alex E.; Esh, Chera L.; Kokjohn, Tyler A.; Castaño, Eduardo M.; Van Vickle, Gregory D.; Kalback, Walter M.; Patton, R. Lyle; Luehrs, Dean C.; Daugs, Ian D.; Kuo, Yu Min; Emmerling, Mark R.; Soares, Holly; Quinn, Joseph F.; Kaye, Jeffrey; Connor, Donald J.; Silverberg, Nina B.; Adler, Charles Howard; Seward, James D.; Beach, Thomas G.; Sabbagh, Marwan N.

In: Alzheimer's and Dementia, Vol. 5, No. 1, 01.2009, p. 18-29.

Research output: Contribution to journalArticle

Roher, AE, Esh, CL, Kokjohn, TA, Castaño, EM, Van Vickle, GD, Kalback, WM, Patton, RL, Luehrs, DC, Daugs, ID, Kuo, YM, Emmerling, MR, Soares, H, Quinn, JF, Kaye, J, Connor, DJ, Silverberg, NB, Adler, CH, Seward, JD, Beach, TG & Sabbagh, MN 2009, 'Amyloid beta peptides in human plasma and tissues and their significance for Alzheimer's disease', Alzheimer's and Dementia, vol. 5, no. 1, pp. 18-29. https://doi.org/10.1016/j.jalz.2008.10.004
Roher, Alex E. ; Esh, Chera L. ; Kokjohn, Tyler A. ; Castaño, Eduardo M. ; Van Vickle, Gregory D. ; Kalback, Walter M. ; Patton, R. Lyle ; Luehrs, Dean C. ; Daugs, Ian D. ; Kuo, Yu Min ; Emmerling, Mark R. ; Soares, Holly ; Quinn, Joseph F. ; Kaye, Jeffrey ; Connor, Donald J. ; Silverberg, Nina B. ; Adler, Charles Howard ; Seward, James D. ; Beach, Thomas G. ; Sabbagh, Marwan N. / Amyloid beta peptides in human plasma and tissues and their significance for Alzheimer's disease. In: Alzheimer's and Dementia. 2009 ; Vol. 5, No. 1. pp. 18-29.
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AU - Van Vickle, Gregory D.

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AU - Connor, Donald J.

AU - Silverberg, Nina B.

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