Evaluation of Apolipoprotein E Fragmentation as a Biomarker for Alzheimer's Disease

Recent studies have supported a role for the proteolytic cleavage of apolipoprotein E4 (APOE4) as a potential mechanism for the enhanced dementia risk associated with Alzheimer's disease. To determine whether APOE4 fragmentation is correlated with AD, ELISA assays were performed with cerebral spinal fluid (CSF) and plasma samples utilizing an antibody that specifically detects a 17 kDa amino-terminal fragment (p17) of APOE (nApoECF antibody). In CSF samples, levels of APOE fragmentation were minimal in both neuropathological normals (NPNs) and AD cases and there were no significant differences between the two cohorts across APOE genotypes. Similar results were found in plasma samples where the p17 APOE fragment comprised only 8.4% of the total level of identified APOE. As with CSF, there were no significant differences found between NPNs and AD cases in terms of the amount of nApoECF quantified. Taken together, these results suggest that the p17 amino-terminal fragment of APOE is not correlated with AD or APOE genotype in the plasma or CSF.