In this study, we evaluated the effect of CSF phosphorylated tau 181 (pTau181) and β-amyloid 1-42 (Aβ1–42) burden, as well as their ratio, on cortical NODDI and MAP-MRI microstructural measures in largely preclinical, cognitively unimpaired (69.7% CU) or mildly cognitively impaired (27.3% MCI) participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). The gene discussed is MAPT; the disease is Alzheimer disease.