A new metabolomic workflow for early detection of Alzheimer's disease

Alzheimer's disease (AD) is the most prevalent cause of dementia among older people. Although AD probably starts 20-30 years before first clinical symptoms become noticeable, nowadays it cannot be diagnosed accurately in its early stages. In this work, we present a new MS-based metabolomic approach based on the use of ultra-high performance liquid chromatography-time-of-flight mass spectrometry (UHPLC-TOF MS) to investigate cerebrospinal fluid (CSF) samples from patients with different AD stages. With the aim to obtain wide metabolome coverage two different chromatographic separation modes, namely reversed phase (RP) and hydrophilic interaction chromatography (HILIC), were used. RP/UHPLC-MS and HILIC/UHPLC-MS methods were optimized and applied to analyze CSF samples from 75 patients related to AD progression. Significant metabolic differences in CSF samples from subjects with different cognitive status related to AD progression were detected using this methodology, obtaining a group of potential biomarkers together with a classification model by means of a multivariate statistical analysis. The proposed model predicted the development of AD with an accuracy of 98.7% and specificity and sensitivity values above of 95%. © 2013 Elsevier B.V.This work was supported by: Projects AGL2011-29857-C03-01, Gun ochBertilStohnesStiftelse, KarolinskaInstitutets fund for geriatric research, StiftelsenGamlaTjanarinnor, Stiftelsen Dementia, Swedish Alzheimer Foundation, Swedish Brain Foundation and the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and the Karolinska Institute. C.I. thanks the MEC for her FPI and stay abroad fellowships.Peer Reviewe