P2-133: Determination of tau, phospho-tau and Abeta1-42 levels in cerebrospinal fluid of patients as a help for the early diagnosis of AD: The french experience in lille

Abstract

According to the clinical conditions, Alzheimer's disease (AD) cannot be diagnosed until dementia is present. New diagnostic tools are needed for the early diagnosis of incipient AD and quantification of cerebrospinal fluid (CSF) biomarkers is of great interest. To determine the diagnostic value of CSF Tau, P–tau and Aβ1–42 in AD versus non–AD patients (MCI patients, non demented control subjects and demented non–AD patients) referred to the Lille Memory Clinic since 2004. Levels of total Tau protein, its phosphorylated form on Thr181 P–tau (P–Tau) and amyloid β1–42 (Aβ1–42) were determined using commercially available sandwich ELISA kits (Innogenetics, Gent, Belgium). One hundred twenty two patients were included: 36 non demented controls, 27 AD patients, 8 MCI (with mild cognitive impairment) and 51 non Alzheimer dementia (3 vascular dementia,7 LBD, 5PSP, 7 CBD, 3 DFT, 4 dementia with parkinsonism and 24 other dementia). In AD patients CSF Aβ1–42 was significantly lower (350 pg/ml) than in non–AD subjects (574 pg/ml), whereas CSF total tau and CSF P–tau were significantly higher (respectively 422 and 58 pg/ml) in AD patients compared to non–AD (respectively 284 and 37 pg/ml). Six MCI have at least one of the three biomarkers that was altered. To distinguish AD patients from non–AD patients sensitivity of Aβ1–42, tau, P–tau and the combination of the three markers were 76%, 43%, 38% and 29% and their specificity were 36%, 95%, 95% and 97% respectively. Their positive predictive values were 39%, 82%, 80% and 86% and their negative predictive values were 74%, 76%, 74% and 72%. CSF tau and P–tau levels, though a low sensitivity have a high specificity, useful for the diagnosis of AD. Determination of Aβ1–42 levels lacks specificity and is more difficult to standardize. Two CSF biomarkers, tau and P–tau have powerful predictive values useful for the diagnosis of Alzheimer's disease. The interest of the biomarkers for the prediction of conversion of MCI to AD will be determined by a longitudinal study.