Performance of Aβ1-40, Aβ1-42, Total Tau, and Phosphorylated Tau as Predictors of Dementia in a Cohort of Patients with Mild Cognitive Impairment

Mild cognitive impairment (MCI) is a common condition in the elderly which may remain stable along time (MCI-MCI) or evolve into Alzheimer's disease (MCI-AD) or other dementias. Cerebrospinal fluid (CSF) classical biomarkers, i.e., amyloid-beta 1-42 (A beta(1-42)), total tau (t-tau), and phosphorylated tau (p-tau) reflect the neuropathological changes taking place in AD brains, thus disclosing the disease in its prodromal phase. With the aim to evaluate the power of each biomarker and/or their combination in predicting AD progression, we have measured CSF A beta(1-40), A beta(1-42), t-tau, and p-tau in patients with AD, MCI-MCI, MCI-AD, and other neurological diseases without dementia (OND) followed up for four years. A beta(1-42) levels were significantly lower in AD and MCI-AD than in MCI-MCI. T-tau and p-tau levels were significantly increased in AD and MCI-AD versus OND and MCI-MCI. The A beta(1-42)/A beta(1-40) ratio showed a significant decrease in AD and MCI-AD as compared to MCI-MCI. Both A beta(1-42)/t-tau and A beta(1-42)/p-tau ratios showed significantly decreased values in AD and MCI-AD with respect to OND and MCI-MCI. A beta(1-42)/p-tau ratio was the best parameter for discriminating MCI-AD from MCI-MCI (sensitivity 81%, specificity 95%), being also correlated with the annual change rate in the Mini Mental State Examination annual change rate score (MMSE-ACR, r(S)=-0.71, p<0.0001). Survival analysis showed that 81% of MCI with a low A beta(1-42)/p-tau ratio (<1372) progressed to AD. The best model of logistic regression analysis retained A beta(1-42) and p-tau (sensitivity 75%, 95%CI: 70-80%; specificity 96%, 95%CI: 94-98%). We can conclude that A beta(1-42) and p-tau reliably predict conversion to AD in MCI patients.