Relationships among cerebrospinal fluid biomarkers in dementia of the Alzheimer type

Cerebrospinal fluid (CSF) contains proteins known to be involved in the pathogenesis of Alzheimer disease (AD), including amyloid-related proteins, tau protein and apolipoprotein E. While the CSF concentrations of these proteins have been compared in subjects with and without dementia of the Alzheimer type (DAT), they have not been simultaneously assessed in carefully staged DAT subjects and control subjects to examine correlations among them. In this study, CSF concentrations of soluble amyloid precursor protein (sAPP), two forms of beta-amyloid protein (Abeta(total) and Abeta(1-42)), tau, and apolipoprotein E were assessed in subjects with (n = 33) and without (n = 11) DAT. Direct correlations were found between CSF concentrations of sAPP and tau and Abeta(total), and between apolipoprotein E and Abeta(total) within the DAT subjects and within the combined group of DAT and control subjects. A weak inverse correlation was also found between CSF concentrations of tau and Abeta(1-42) within the combined group of DAT and control subjects. Moreover, increased severity of dementia was correlated with increased CSF tau concentrations and decreased sAPP and Abeta(total) concentrations. Increased CSF concentrations of tau significantly discriminated DAT and control subjects, as did the ratios of tau to Abeta(total) and tau to Abeta(1-42).