Work

Quantification of total apolipoprotein E and its isoforms in cerebrospinal fluid from patients with neurodegenerative diseases

Year: 2020

Type: article

Abstract: BACKGROUND: The human APOE gene, which codes for apolipoprotein E (apoE), has three major polymorphic alleles: ε2, ε3, and ε4 that give rise to amino acid substitutions. APOE-ε4 is a strong risk factor of sporadic Alzheimer's disease (AD) but the reason why is still unknown despite intense research for more than 20 years. The aim of the study was to investigate if the concentrations of total apoE and the specific apoE isoforms in cerebrospinal fluid (CSF) differ between various neurodegenerative diseases and control individuals, as well as among the APOE genotypes. METHODS: CSF concentration ratio cut-off into Aβ positive (Aβ+, < 0.091) and Aβ negative (Aβ-, > 0.091) groups. RESULTS: Even though there was a significant increase of total apoE in the amyloid β-positive (Aβ+) group compared with amyloid β-negative (Aβ-) individuals (p < 0.001), the magnitude of the effect was very small (AUC = 0.55). Moreover, CSF total apoE concentrations did not differ between Aβ- CU controls and clinically diagnosed AD patients. There was a difference in concentration between isoforms in heterozygous individuals in an isoform-dependent manner (E2 < E3 < E4) (p < 0.001, AUC = 0.64-0.69), and these associations remained when dichotomizing the samples into Aβ+ and Aβ- groups (p < 0.01, AUC = 0.63-0.74). In the cohort with follow-up samples, neither total apoE nor isoform-specific apoE concentrations differed between the two time points (p > 0.05). CONCLUSIONS: The results indicate that neither the concentrations of total apoE nor the different apoE isoforms in CSF are associated with APOE-ε4 carrier status, Aβ status, or clinical dementia diagnoses.

Source: Alzheimer s Research & Therapy

DOI: 10.1186/s13195-020-00585-7