Novel panel of cerebrospinal fluid biomarkers for the prediction of progression to Alzheimer dementia in patients with mild cognitive impairment

Objective: To use proteomic analysis of cerebrospinal fluid to discover novel proteins and peptides able to differentiate between patients with stable mild cognitive impairment (MCI) and those who will progress to Alzheimer disease (AD). Design: Baseline cerebrospinal fluid samples from patients with MCI and healthy controls were profiled using surface-enhanced laser desorption/ionization time-offlight mass spectrometry. Setting: Memory disorder clinic. Participants: Patients with MCI (n = 113), of whom 56 were cognitively stable and 57 progressed to AD with dementia during a 4- to 6-year follow-up, as well as 28 healthy controls who were followed up for 3 years. Main Outcome Measure: During follow-up, 57 patients progressed to AD and 56 patients had stable MCI. Cerebrospinal fluid from these 2 groups of patients was compared using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. Results: We identified a panel of 17 potential biomarkers that could distinguish between patients with stable MCI and patients with MCI who progressed to AD. We have positively identified and characterized 5 of the potential biomarkers. Conclusions: Proteomic profiling of cerebrospinal fluid provided a novel panel of 17 potential biomarkers for prediction of MCI progression to AD. The 5 identified biomarkers are relevant to the pathogenesis of AD and could help gain an understanding of the molecular pathways in which they may function.