Higher plasma cholesterol levels are associated with lower Parkinson's disease (PD) risk. Apolipoprotein A-1 (ApoA-1) is a surface marker of brain HDL-like particles associated with the time of PD onset. Clinical correlates of serum Apolipoprotein A1 levels with structural brain connectivity in PD-related disorders remains unclear. Here, we applied a novel diffusion-weighted imaging approach [Diffusion Magnetic Resonance Imaging (MRI) Connectometry] to explore the association between ApoA-1 and structural brain connectivity in PD. Participants involved in this research were recruited from Parkinson's Progression Markers Initiative (PPMI). Diffusion MRI connectometry was conducted using a multiple regression against apoA-1 for 36 patients with DTI measurements available in the baseline visit. Fiber results of the connectometry were then reconstructed for each patient, and diffusion parameters were extracted and regressed against apoA-1 levels. Connectometry results revealed the subgenual cingulum to be associated with ApoA-1, with different FDR yields. This result was further supported by significant negative correlation of Quantitative Anisotropic (QA) of left subgenual cingulum (Pearson's coefficient = -0.398, p = 0.020) and Generalized Fractional Anisotropic (GFA) of right subgenual cingulum (Pearson's coefficient -0.457, p = 0.007) with plasma apoA-1 levels, in a multiple regression model with age and sex. The subgenual cingulum encompasses fibers from the anterior cingulate cortex and anterior thalamus. These structures are involved in PD-associated psychosis and executive cognitive decline. We demonstrated for the first time that apoA-1, as a blood marker, can predict microstructural changes in white matter regions in PD patients with undisturbed cognition and mild motor disability.