The Y145Stop mutant of human prion protein, huPrP23-144, has been linked to PrP cerebral amyloid angiopathy, an inherited amyloid disease, and also serves as a valuable in vitro model for investigating the molecular basis of amyloid strains. Prior studies of huPrP23-144 amyloid by magic-angle-spinning (MAS) solid-state NMR spectroscopy revealed a compact beta-rich amyloid core region near the C-terminus and an unstructured N-terminal domain. Here, with the focus on understanding the higher-order architecture of huPrP23-144 fibrils, we probed the intermolecular alignment of beta-strands within the amyloid core using MAS NMR techniques and fibrils formed from equimolar mixtures of N-15-labeled protein and C-13-huPrP23-144 prepared with [1,3-C-13(2)] or [2-C-13]glycerol. Numerous intermolecular correlations involving backbone atoms observed in 2D N-15-C-13 spectra unequivocally suggest an overall parallel in-register alignment of the beta-sheet core. Additional experiments that report on intermolecular N-15-(CO)-C-13 and N-15-C-13 alpha dipolar couplings yielded an estimated strand spacing that is within similar to 10% of the distances of 4.7-4.8 angstrom typical for parallel beta-sheets.