Herein, we aimed to investigate whether plasma SHBG could predict neurodegeneration and clinical progression in prodromal AD: 1) we first tested whether plasma SHBG was associated with CSF AD biomarkers in Chinese Alzheimer’s Biomarker and LifestylE (CABLE) study; 2) we next explored the values of plasma SHBG in predicting CSF AD core biomarkers, imaging, cognition, and AD risk in Alzheimer’s disease Neuroimaging Initiative (ADNI) cohort. The gene discussed is SHBG; the disease is Alzheimer disease.