APOE4 carriership status influences [11C]PiB white matter retention in cognitively healthy older adults

Purpose: The objective of this study was to assess whether APOE4 carriership status affects white matter (WM) [¹¹C]PiB positron emission tomography (PET) retention in cognitively healthy older adults, as a potential indicator of myelin integrity.

Methods: We explored WM [¹¹C]PiB retention of 101 participants (non-carriers, n = 40; APOE3/4 carriers, n = 40; APOE4/4 carriers, n = 21) and its association with fractional anisotropy, a diffusion tensor imaging measure reflecting WM microstructure. WM [¹¹C]PiB retention was assessed in voxel-wise analysis and within normal-appearing white matter (NAWM) and white matter hyperintensities (WMHs) as regions-of-interest.

Results: [¹¹C]PiB retention was lower in WMHs than NAWM (p_t-test < 0.001). In NAWM, APOE4/4 and APOE3/4 carriers showed reduced [¹¹C]PiB retention compared to non-carriers (p_ANCOVA = 0.040, among all groups), while there were no significant differences in [¹¹C]PiB retention within regions of WMHs (p_ANCOVA = 0.11). APOE4/4 carriers had lower WM [¹¹C]PiB retention than non-carriers in voxel-wise analysis (p_FWE < 0.05). WM [¹¹C]PiB retention was not associated with fractional anisotropy, suggesting different pathological pathways.

Conclusion: A decrease in NAWM [¹¹C]PiB retention is suggestive of myelin damage prior to the onset of cognitive decline in APOE4 homozygotes.