Prediction and longitudinal study of CSF biomarkers in mild cognitive impairment

ObjectivesTo longitudinally evaluate five cerebrospinal fluid (CSF) biomarkers in the transition from mild cognitive impairment (MCI) to Alzheimer's disease (AD).MethodsA baseline and 2-year follow-up clinical and CSF study of 86 subjects, including 22 MCI patients that declined to AD (MCI-AD), 43 MCI that did not deteriorate (MCI-MCI) and 21 controls (NL-NL). All subjects were studied for total and phosphorylated tau (T-tau, P-tau231), amyloid beta (Aβ) Aβ42/Aβ40 ratio, isoprostane (IP) as well as P-tau231/Aβ42/40 and T-tau/Aβ42/40 ratios.ResultsAt baseline and at follow-up MCI-AD showed higher levels P-tau231, T-tau, IP, P-tau231/Aβ42/40 and T-tau/Aβ42/40 ratios and lower Aβ42/Aβ40 than MCI-MCI or NL-NL. Baseline P-tau231 best predicted MCI-AD (80%, p < 0.001) followed in accuracy by P-tau231/Aβ42/40 and T-tau/Aβ42/40 ratios (both 75%, p's < 0.001), T-tau (74%, p < 0.001), Aβ42/Aβ40 (69%, p < 0.01), and IP (68%, p < 0.01). Only IP showed longitudinal effects (p < 0.05).ConclusionsP-tau231 is the strongest predictor of the decline from MCI to AD. IP levels uniquely show longitudinal progression effects. These results suggest the use of CSF biomarkers in secondary prevention trials.