Rapid Progression from Mild Cognitive Impairment to Alzheimer's Disease in Subjects with Elevated Levels of Tau in Cerebrospinal Fluid and the APOE ε4/ε4 Genotype

Background/Aims: Increased cerebrospinal fluid (CSF) tau, decreased CSF amyloid-beta 42 (A beta 42) and the apolipoprotein E gene (APOE) epsilon 4 allele predict progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD). Here, we investigated these markers to assess their predictive value and influence on the rate of disease progression. Methods: Using ELISA, we measured the CSF biomarkers in 47 AD patients, 58 patients with MCI and 35 healthy control subjects. Twenty-eight MCI patients revisited the clinic and half of them progressed to AD during a period of 3-12 years. Results: The expected changes in CSF total(T)-tau, phosphorylated (P)-tau and A beta 42 levels were found in AD, confirming the diagnostic value of these biomarkers. We were also able to corroborate an increased risk for progression from MCI to AD with elevated CSF T-tau and P-tau and with the presence of the APOE epsilon 4/epsilon 4 genotype, but not with decreased A beta 42. Finally, for the first time we demonstrated that MCI subjects with high CSF T-tau or P-tau and APOE epsilon 4 homozygosity progressed faster from MCI to AD. Conclusions: CSF T-tau and P-tau as well as the APOE epsilon 4/epsilon 4 genotype are robust predictors of AD and are also associated with a more rapid progression from MCI to AD. Copyright (C) 2009 S. Karger AG, Basel