Distinct patterns of apolipoprotein C-I, C-II, and C-III isoforms are associated with markers of Alzheimer's disease

Apolipoproteins C-I, C-II, and C-III interact with ApoE to regulate lipoprotein metabolism and contribute to Alzheimer's disease pathophysiology. In plasma, apoC-I and C-II exist as truncated isoforms, while apoC-III exhibits multiple glycoforms. This study aimed to 1) delineate apoC-I, C-II, and C-III isoform profiles in cerebrospinal fluid (CSF) and plasma in a cohort of nondemented older individuals (n = 61), and 2) examine the effect of APOE4 on these isoforms and their correlation with CSF A beta 42, a surrogate of brain amyloid accumulation. The isoforms of the apoCs were immunoaffinity enriched and measured with MALDI-TOF mass spectrometry, revealing a significantly higher percentage of truncated apoC-I and apoC-II in CSF compared with matched plasma, with positive correlation between CSF and plasma. A greater percentage of mono-sialylated and disialylated apoC-III isoforms was detected in CSF, accompanied by a lower percentage of the two nonsialylated apoC-III isoforms, with significant linear correlations between CSF and plasma. Furthermore, a greater percentage of truncated apoC-I in CSF and apoC-II in plasma and CSF was observed in individuals carrying at least one APOE epsilon 4 allele. Increased apoC-I and apoC-II truncations were associated with lower CSF A beta 42. Finally, mono-sialylated apoC-III was lower, and disialylated apoC-III greater in the CSF of epsilon 4 carriers. Together, these results reveal distinct patterns of the apoCs isoforms in CSF, implying CSF-specific apoCs processing. jlr These patterns were accentuated in APOE epsilon 4 allele carriers, suggesting an association between APOE4 genotype and Alzheimer's disease pathology with apoCs processing and function in the brain.

Automated summary

This study found significantly higher percentages of truncated apoC-I and apoC-II in CSF compared with matched plasma, with positive correlations between them. In addition, there were more mono-sialylated and disialylated apoC-III isoforms in CSF, with significant linear correlations between CSF and plasma. Individuals carrying at least one APOE epsilon 4 allele showed a greater percentage of truncated apoC-I in CSF and apoC-II in plasma and CSF.