Association of LDL cargo proteins with white matter hyperintensity volume in older adults from the atherosclerosis risk in communities study

BackgroundLow-density lipoprotein cholesterol (LDL-C) has been associated with Alzheimer's disease (AD) pathology and other neuroimaging measures, such as brain volume and white matter hyperintensity (WMH) volume.ObjectiveIn this exploratory study, we examined cross-sectional associations between LDL cargo proteins and AD-related outcomes.MethodsWe randomly selected 65 participants without dementia with amyloid PET and brain MRI data available in the Atherosclerosis Risk in Communities. We used a mass spectrometry-based technique to quantify proteins in LDL isolated from plasma collected at the ARIC Visit 5. Linear or logistic regression was applied to evaluate the associations between individual LDL protein or LDL-C and (1) brain amyloid deposition (yes or no), (2) temporal-parietal meta-ROI brain volume (a biomarker of AD-related neurodegeneration), or (3) WMH volume, adjusting for covariates.ResultsParticipants' average age was 76.3 years with a standard deviation of 5.4, and females comprised 53.8% (35 out of 65). The estimated effect sizes of many LDL protein's associations with these neuroimaging measures were larger than that of LDL-C. The strongest association was higher LDL apolipoprotein C1 (apoC1) and lower WMH volume. Each SD increment of LDL apoC1 LDL was associated with a lower WMH volume of 7243.1 mm³ (95% CI [-10482.0, -4004.1]; a BH-adjusted p = 0.002). In comparison, each SD increment of LDL-C (in mg/dL) was associated with a lower WMH volume of 1676.1 mm³ (95% CI [-5425.9, 2073.7]; a BH-adjusted p of 0.90)<b>.</b>ConclusionsThis study suggests that increased LDL apoC1 was linked to decreased WMH volume in older adults without dementia.