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Original Contribution | ONLINE FIRST

β-Amyloid Dynamics in Human Plasma ONLINE FIRST

Yafei Huang, PhD; Rachel Potter, BA; Wendy Sigurdson, MSN; Tom Kasten, PhD; Rose Connors, BA; John C. Morris, MD; Tammie Benzinger, MD; Mark Mintun, MD; Tim Ashwood, PhD; Mats Ferm, PhD; Samantha L. Budd, PhD; Randall J. Bateman, MD
Arch Neurol. 2012;():1-7. doi:10.1001/archneurol.2012.1810.
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Objectives  To investigate dynamic changes in human plasma β-amyloid (Aβ) concentrations, evaluate the effects of aging and amyloidosis on these dynamics, and determine their correlation with cerebrospinal fluid (CSF) Aβ concentrations.

Design  A repeated plasma and CSF sampling study.

Setting  The Washington University School of Medicine in St Louis, Missouri.

Participants  Older adults with amyloid deposition (Amyloid+), age-matched controls without amyloid deposition (Amyloid), and younger normal controls (YNCs) were enrolled for the study.

Main Outcome Measures  Hourly measurements of plasma Aβ were compared between groups by age and amyloidosis. Plasma Aβ and CSF Aβ concentrations were compared for correlation, linear increase, and circadian patterns.

Results  Circadian patterns were observed in plasma Aβ, with diminished amplitudes with aging. Linear increase of Aβ was only observed for CSF Aβ in the YNC and Amyloid groups, but not in the Amyloid+ group. No linear increase was observed for plasma Aβ. No significant correlations were found between plasma and CSF Aβ concentrations.

Conclusions  Plasma Aβ, like CSF, demonstrates a circadian pattern that is reduced in amplitude with increasing age but is unaffected by amyloid deposition. However, we found no evidence that plasma and CSF Aβ concentrations were related on an hourly or individual basis.

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Figures

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Grahic Jump Location

Figure 1. Cerebrospinal (CSF) β-amyloid 40 (Aβ40) (A) and Aβ42 (B) concentrations linearly increase in the younger normal control (YNC) and age-matched control without amyloid deposition (Amyloid) groups. However, in the older adult with amyloid deposition (Amyloid+) group, the linear increase of CSF Aβ42 was absent and the linear increase of CSF Aβ40 was diminished. In contrast, plasma Aβ40 (A) and Aβ42 (B) concentrations did not have a linear rise in any of the 3 groups.

Place holder to copy figure label and caption
Grahic Jump Location

Figure 2. β-Amyloid (Aβ) diurnal patterns diminish with increased age. The diurnal amplitude of plasma Aβ40 (A), plasma Aβ42 (B), cerebrospinal (CSF) Aβ40 (C), and CSF Aβ42 (D) was decreased by approximately half in the older groups (age-matched control without amyloid deposition [Amyloid] and older adult with amyloid deposition [Amyloid+]) compared with the younger group, regardless of amyloid deposition. Data are group averaged mean-adjusted Aβ concentrations over time. YNC indicates younger normal control.

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