An association of CSF apolipoprotein E glycosylation and amyloid-beta 42 in individuals who carry the APOE4 allele.

Autor: Meuret CJ; University of Southern California, 2250 Alcazar St, Rm 210, Los Angeles, CA, 90033, USA., Hu Y; Isoformix Inc., 9830 S. 51. St. Suite B-113, Phoenix, AZ, 85044, USA., Smadi S; University of Southern California, 2250 Alcazar St, Rm 210, Los Angeles, CA, 90033, USA., Bantugan MA; University of Southern California, 2250 Alcazar St, Rm 210, Los Angeles, CA, 90033, USA., Xian H; University of Southern California, 2250 Alcazar St, Rm 210, Los Angeles, CA, 90033, USA., Martinez AE; University of Southern California, 2250 Alcazar St, Rm 210, Los Angeles, CA, 90033, USA., Krauss RM; University of California, San Francisco, CA, USA., Ma QL; University of Southern California, 2250 Alcazar St, Rm 210, Los Angeles, CA, 90033, USA., Nedelkov D; Isoformix Inc., 9830 S. 51. St. Suite B-113, Phoenix, AZ, 85044, USA. dobrin.nedelkov@isoformix.com., Yassine HN; University of Southern California, 2250 Alcazar St, Rm 210, Los Angeles, CA, 90033, USA. hyassine@usc.edu.
Jazyk: angličtina
Zdroj: Alzheimer's research & therapy [Alzheimers Res Ther] 2023 May 23; Vol. 15 (1), pp. 96. Date of Electronic Publication: 2023 May 23.
DOI: 10.1186/s13195-023-01239-0
Abstrakt: Carrying the apolipoprotein E (ApoE) Ɛ4 allele is associated with an increased risk of cerebral amyloidosis and late-onset Alzheimer's disease, but the degree to which apoE glycosylation affects its development is not clear. In a previous pilot study, we identified distinct total and secondary isoform-specific cerebral spinal fluid (CSF) apoE glycosylation profiles, with the E4 isoform having the lowest glycosylation percentage (E2 > E3 > E4). In this work, we extend the analysis to a larger cohort of individuals (n = 106), utilizing matched plasma and CSF samples with clinical measures of AD biomarkers. The results confirm the isoform-specific glycosylation of apoE in CSF, resulting from secondary CSF apoE glycosylation patterns. CSF apoE glycosylation percentages positively correlated with CSF Aβ 42 levels (r = 0.53, p < 0.0001). These correlations were not observed for plasma apoE glycosylation. CSF total and secondary apoE glycosylation percentages also correlated with the concentration of CSF small high-density lipoprotein particles (s-HDL-P), which we have previously shown to be correlated with CSF Aβ 42 levels and measures of cognitive function. Desialylation of apoE purified from CSF showed reduced Aβ 42 degradation in microglia with E4 > E3 and increased binding affinity to heparin. These results indicate that apoE glycosylation has a new and important role in influencing brain Aβ metabolism and can be a potential target of treatment.
(© 2023. The Author(s).)
Databáze: MEDLINE
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