Work

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

Year: 2025

Type: article

Abstract: The objective of this study was to assess whether APOE4 carriership status affects white matter (WM) [ 11 C]PiB positron emission tomography (PET) retention in cognitively healthy older adults, as a potential indicator of myelin integrity. We explored WM [ 11 C]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 [ 11 C]PiB retention was assessed in voxel-wise analysis and within normal-appearing white matter (NAWM) and white matter hyperintensities (WMHs) as regions-of-interest. [ 11 C]PiB retention was lower in WMHs than NAWM (p t-test < 0.001). In NAWM, APOE4/4 and APOE3/4 carriers showed reduced [ 11 C]PiB retention compared to non-carriers (p ANCOVA = 0.040, among all groups), while there were no significant differences in [ 11 C]PiB retention within regions of WMHs (p ANCOVA = 0.11). APOE4/4 carriers had lower WM [ 11 C]PiB retention than non-carriers in voxel-wise analysis (p FWE < 0.05). WM [ 11 C]PiB retention was not associated with fractional anisotropy, suggesting different pathological pathways. A decrease in NAWM [ 11 C]PiB retention is suggestive of myelin damage prior to the onset of cognitive decline in APOE4 homozygotes. • [ 11 C]PiB white matter SUVR is lower in cognitively healthy APOE4/4 than non-carriers. • This decrease is suggestive of a reduction in myelin integrity. • White matter [ 11 C]PiB retention was not associated with fractional anisotropy. • Methodological considerations of [ 11 C]PiB as a marker of myelination are discussed.

Source: Neurobiology of Disease

DOI: 10.1016/j.nbd.2025.107140