Cerebrospinal Fluid Soluble Amyloid-β Protein Precursor as a Potential Novel Biomarkers of Alzheimer's Disease

In this report, we confirm our previous findings of increased concentrations of soluble amyloid-beta protein precursor (sA beta PP) in cerebrospinal fluid (CSF) of patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI) in a large cohort of patients (n = 314), not overlapping with those of our previous study, and we extend our observations by including a control group of participants with normal cognition. In addition, we investigate the effects of age, the APOE epsilon 4 genotype, and the blood-CSF barrier function on the concentrations of sA beta PP alpha and sA beta PP beta. The study participants were categorized according to clinical-neuropsychological criteria, supported by CSF neurochemical dementia diagnostics (NDD) analyses. sA beta PP alpha concentrations in the AD group (132.0 +/- 44.8) were significantly higher than in the control group (105.3 +/- 37.3, p < 0.0005) but did not differ from the MCI-AD group (138.5 +/- 39.5, p = 0.91). The MCI-AD group differed significantly from the MCI-O (97.3 +/- 34.3, p < 0.05) group. There was no difference between the control and the MCI-O groups (p = 0.94). Similarly, sA beta PP beta concentrations in the AD group (160.2 +/- 54.3) were significantly higher than in the control group (129.9 +/- 44.6, p < 0.005) but did not differ from the MCI-AD group (184.0 +/- 56.4, p = 0.20). The MCI-AD group differed significantly from the MCI-O (127.8 +/- 46.2, p < 0.05) group. There was no difference between the control and the MCI-O groups (p > 0.99). We observed highly significant correlation of the two sA beta PP forms. Age and the CSF-serum albumin ratio were significant albeit weak predictors of the sA beta PP alpha and sA beta PP alpha concentrations, while carrying the APOE epsilon 4 allele did not influence the levels of the sA beta PP forms. Taken together, the results strongly suggest that CSF sA beta PP concentrations may be considered as an extension of already available NDD tools.