Presenter of 1 Presentation
LOWER CSF APOE GLYCOSYLATION ASSOCIATES WITH MEASURES OF AD BIOMARKERS
Abstract
Aims
Background: The mechanisms of how APOE4 allele (APOE4) increases the risk of Alzheimer’s disease (AD) pathology have not been fully elucidated. In cerebrospinal fluid (CSF), apoE is heavily glycosylated but its contributions to AD pathology is not known. ApoE’s glycosylation affects its binding to lipids and abeta peptides.
Methods
Total glycosylation and isoform-specific glycosylation were analyzed in plasma and CSF from a group of older individuals (n=106) from the University of Southern California ADRC cohort, grouped into cognitively normal individuals (n=75), those with mild cognitive impairment (n=14) and with AD dementia (n=17).
Results
In heterozygous individuals, the apoE3/E2, E4/E2, and E4/E3 isoform ratios were all significantly lower in plasma compared to CSF. The ratio of glycosylated to total apoE was greater in CSF compared to plasma for all apoE isoforms. In CSF but not plasma, ApoE4 was 35% and 25% less glycosylated (P<0.001) than ApoE2 and ApoE3, respectively. The % of secondary glycosylation was positively correlated with CSF Ab42 levels (R=0.55, p<0.001) and negatively correlated with CSF total Tau (R=-0.38, p=0.001). Patients with AD dementia had lower apoE % glycosylation than individuals with MCI (p=0.008).
Conclusions
Brain ApoE4 is less glycosylated than ApoE3 or ApoE2, and its degree of glycosylation correlates with markers of AD pathology. Ongoing experiments are delineating the effects of ApoE glycosylation on its functions. ApoE4 glycosylation may represent a newer target of treatment in AD.
