While matched plasma and CSF were not available from the present cohort, considering our previous plasma (Ashraf et al., 2020a) and current CSF HPX findings, we suggest the decreased CSF HPX associated with decreased CSF Aβ and increased ptau, and disease progression (albeit not MCI conversion to AD), may result from: abnormally greater HPX export from the CSF to the plasma compartment; decreased neuroglial HPX synthesis; and/or increased brain parenchymal low density lipoprotein receptor-related protein 1 (LRP1)-mediated scavenging (Hvidberg et al., 2005). Here, LRP1 is linked to Alzheimer disease.