Rapid Progression from Mild Cognitive Impairment to Alzheimer’s Disease in Subjects with Elevated Levels of Tau in Cerebrospinal Fluid and the <i>APOE </i>ε<i>4</i>/ε<i>4</i> Genotype

<i>Background/Aims:</i> Increased cerebrospinal fluid (CSF) tau, decreased CSF amyloid-β42 (Aβ42) and the apolipoprotein E gene <i>(APOE) </i>ε<i>4</i> 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. <i>Methods:</i> 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. <i>Results:</i> The expected changes in CSF total (T)-tau, phosphorylated (P)-tau and Aβ42 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 <i>APOE </i>ε<i>4/</i>ε<i>4</i> genotype, but not with decreased Aβ42. Finally, for the first time we demonstrated that MCI subjects with high CSF T-tau or P-tau and <i>APOE </i>ε<i>4</i> homozygosity progressed faster from MCI to AD. <i>Conclusions:</i> CSF T-tau and P-tau as well as the <i>APOE </i>ε<i>4/</i>ε<i>4</i> genotype are robust predictors of AD and are also associated with a more rapid progression from MCI to AD.