Apolipoprotein C proteins in plasma non‐high‐density lipoprotein fractions and development of Alzheimer’s disease, central arterial stiffness, and cerebral small vessel disease in older adults

Background Plasma non-high-density lipoproteins impact development of central arterial stiffness and cerebral small vessel disease (cSVD), significantly contributing to Alzheimer’s (AD) related dementias (ADRDs) through an increase in amyloid beta (Aβ) burden acceleration atrophy susceptible brain regions. We sought identify proteins three non-HDL plasma (very-low density lipoprotein [VLDL], intermediate-density [IDL], low-density [LDL]) their cross-sectional associations with deposition, stiffness, neuroimaging features cSVD (e.g., white matter hyperintensity volume), volumes AD cSVD, incidence dementia. Method samples from 66 participants the Atherosclerosis Risk Communities (ARIC) study were fractionated isolate VLDL, IDL, LDL analyzed using label-free liquid chromatography-mass spectrometry (LC-MS) Data-Independent Acquisition. Acquired MS spectra processed Spectronaut™ give protein identification relative abundances calculated R. Linear regression models used examine between IDL or deposition (measured by PET scan), hyperintensities (WMH) volume MRI), (carotid-femoral heart-femoral pulse wave velocity), AD-signature region, frontal, parietal, hippocampal region Regression adjusted for age, sex, race, number APOε4 alleles, cholesterol level (if applicable). Additionally, differential analysis (student’s t-test) was compare elevated versus normal deposition. Result identified 50, 78, 81 LDL, respectively. The most significant findings were: 1) higher levels apolipoprotein C associated lower WMH less stiffness; 2) dementia; 3) Conclusion These results suggest possible role present non-HDL-lipoproteins AD, cSVD.