β-amyloid dynamics in human plasma

Abstract

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.

Figure 1

CSF Aβ40 (A) and Aβ42 (B) concentrations linearly increase in YNC and Amyloid − groups. However, in the 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) did not have a linear rise in any of the three groups.

Figure 2

Aβ diurnal patterns diminish with increased age. The diurnal amplitude of Plasma Aβ40 (A), Plasma Aβ42 (B), CSF Aβ40 (C), and CSF Aβ42(D) were decreased by approximately half in the older groups (Amyloid − and Amyloid +) compared to the younger group, regardless of amyloid deposition. Data are group averaged mean-adjusted Aβ levels over time.