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

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 Aβ_1–40 and Aβ_1–42 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 Aβ_1–40, Aβ_1–42, and Aβ_1–40/Aβ_1–42 with [¹¹C]PiB uptake.

Results

In APOE ε4− but not ε4+ participants, positive relationships between plasma Aβ_1–40/Aβ_1–42 and [¹¹C]PiB uptake were observed. Modeling the interaction of APOE and plasma Aβ_1–40/Aβ_1–42 improved the explained variance in [¹¹C]PiB binding compared with using APOE and plasma Aβ_1–40/Aβ_1–42 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.

Fig. 1. (A–D) Scatterplots of plasma Aβ_1–40/Aβ_1–42 vs average regional [¹¹C]PiB uptake from the (Average regional [¹¹C]PiB uptake = Plasma Aβ_1–40/Aβ_1–42 + APOE ε4 status + [Plasma Aβ_1–40/Aβ_1–42 × APOE ε4 status]) model (A and B), and plasma Aβ_1–40/Aβ_1–42 vs mean [¹¹C]PiB uptake from the cluster identified in the (Voxel [¹¹C]PiB uptake = Plasma Aβ_1–40/Aβ_1–42 + APOE ε4 status + [Plasma Aβ_1–40/Aβ_1–42 × APOE ε4 status]) model (C and D). Aβ, amyloid beta; PiB, Pittsburgh compound B; APOE, apolipoprotein E.

Figure options

Fig. 2. Brain regions (R, right; L, left) identified in the (Voxel [¹¹C]PiB uptake = Plasma Aβ_1–40/Aβ_1–42 + APOE ε4 status + [Plasma Aβ_1–40/Aβ_1–42 × APOE ε4 status]) model (voxel-level threshold of P < .005 [uncorrected], cluster size ≥ 200 voxels). The red-to-yellow scale indicates increasing statistical significance of association. PiB, Pittsburgh compound B; Aβ, amyloid beta; APOE, apolipoprotein E.