Biomarker profiles of Alzheimer's disease and dynamic of the association between cerebrospinal fluid levels of β-amyloid peptide and tau

Objective To investigate the relationship between cerebrospinal fluid (CSF) 6-amyloid peptide (A(342) and CSF Tau in a large population of patients referred to memory clinics for investigation of cognitive dysfunction. Methods We analyzed Alzheimer's disease (AD) biomarkers in CSF taken from 3565 patients referred to 18 French memory clinics. Patients were classified into four profiles according to levels of CSF biomarkers (A: amyloidosis, N: neurodegeneration). The association between CSF Tau and CSF A642 were analyzed using general linear regression models, in the overall population and stratified by biomarkers profiles. We compared linear and quadratic models using Akaike information criterion. We also assessed change in biomarker profiles in a subset of patients who had 2 assessments of biomarkers. Results CSF Tau was negatively associated with CSF A342 in the overall population, following a non-linear quadratic model. However, the nature of this association was different in the 4 profiles: positive association in A-N- profile, negative association in A-N+ and A+N+ profiles, lack of association in A+N- patients. When considering patients with longitudinal data on profiles, 36% of those initially classified as A-N+ evolved to an A+N+ profile. Conclusions The nature of the association between CSF A beta 42 and CFS Tau depends on the A/N profiles of patients. These results suggest an increase in CSF A beta 42 early in the disease before its decline while tau pathology progresses, this pattern is particularly observed in non-APOE4 subjects. This phenomenon may explain why some patients with neurodegeneration only markers convert to an AD profile (A+N+) over time.