Alterations in the Balance of Amyloid-beta Protein Precursor Species in the Cerebrospinal Fluid of Alzheimer's Disease Patients

摘要

We recently demonstrated that soluble forms of the amyloid-beta protein precursor (sA beta PP) assemble into multimeric complexes in cerebrospinal fluid (CSF), which contributes to the underestimation of specific sA beta PP species when assessed by ELISA. To circumvent this issue, we analyzed by SDS-PAGE large fragments of sA beta PP and their variants in the CSF from Alzheimer's disease (AD; n = 20) and control (n = 20) subjects, probing with specific antibodies against particular domains. Similar levels of sA beta PP alpha and sA beta PP beta protein were found in CSF samples from AD and controls, yet there appeared to be a shift in the balance of the soluble full-length A beta PP (sA beta PPf) species in AD samples, with a decrease in the proportion of the lower (similar to 100 kDa) band relative to the upper (similar to 120 kDa) band. Similar differences were observed in the contribution of the major KPI-immunoreactive A beta PP species. CSF samples also displayed differences in the correlations of A beta PP species with classical AD biomarkers, particularly with respect to the A beta(42) peptide. The differences reveal alterations that probably reflect pathophysiological changes in the brain.