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 β-amyloid protein (Aβ_total and Aβ_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 Aβ_total, and between apolipoprotein E and Aβ_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 Aβ_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 Aβ_total concentrations. Increased CSF concentrations of tau significantly discriminated DAT and control subjects, as did the ratios of tau to Aβ_total and tau to Aβ_1-42.