Performance of Aβ_1-40, Aβ_1-42, 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-β 1-42 (Aβ_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 Aβ_1-40, Aβ _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. Aβ_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 Aβ_1-42/Aβ_1-40 ratio showed a significant decrease in AD and MCI-AD as compared to MCI-MCI. Both Aβ_1-42/t-tau and Aβ_1-42/p-tau ratios showed significantly decreased values in AD and MCI-AD with respect to OND and MCI-MCI. Aβ_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 Aβ_1-42/p-tau ratio (1-42 and p-tau (sensitivity 75%, 95%CI: 70-80%; specificity 96%, 95%CI: 94-98%). We can conclude that Aβ_1-42 and p-tau reliably predict conversion to AD in MCI patients.