Predicting CSF neurogranin and neurofilament light chain protein levels with a neuropathology‐based APOE genetic risk score

Cerebrospinal fluid (CSF) levels of neurogranin, an index of synaptic degeneration, and neurofilament light chain (NfL), an index of neuroaxonal degradation, are both biomarkers of neurodegeneration in Alzheimer’s disease (AD). The presence of APOE is the strongest genetic risk factor for late onset AD and has also been associated with increased CSF neurogranin, a marker of neurodegeneration. To test the association between APOE and CSF biomarkers for neurodegeneration, we used a neuropathology‐based weighted risk score for APOE genotype (APOE‐npscore) and hypothesized that greater AD risk as indexed by the APOE‐npscore would be associated with higher CSF concentrations of neurogranin and NfL.