Spinal Fluid Biomarkers Detect Early Alzheimer's Disease

Abnormal levels of seven proteins in cerebrospinal fluid could be markers for the early stages of Alzheimer's disease (AD), which would improve diagnosis.

Biomarker ions were determined using mass spectroscopy to identify the seven proteins that are diagnostic of prodromal AD which were then followed by bioinformatic analysis that generated a set of potential biomarkers.

Scientists at Nottingham Trent University (Nottingham, UK) analyzed samples of lumbar cerebrospinal fluid (CSF) from 33 clinically diagnosed AD cases, 20 age-matched controls, and 10 mild cognitive impairment (MCI) patients to obtain proteomic profiles.

The panel of seven peptide biomarker ions was able to discriminate AD patients from controls with a median accuracy of 95% (sensitivity 85%, specificity 97%). The panel was identified, in order of predictive ability, as the secreted protein acidic and rich in cysteine (SPARC)-like 1 protein, fibrinogen alpha chain precursor, amyloid-β, apolipoprotein E precursor, serum albumin precursor, keratin type I cytoskeletal 9, and tetranectin.

When the model was applied to an independent blind dataset from MCI patients, the intensity of signals was intermediate between the control and AD patients implying that these markers could potentially predict patients with early neurodegenerative disease. The seven ion diagnostic paradigm was further validated using an independent cohort of samples, where the model was able to classify AD cases from controls with median accuracy of 84.5% (sensitivity 93.3%, specificity 75.7%). Validation by immunoassay was performed on the top three identified markers using the discovery samples and an independent sample cohort, which was from 17 postmortem confirmed AD patients.

Professor Kevin Morgan, from the Human Genomics and Molecular Genetics Institute at Nottingham and the principal author of the study said, "The findings are a new lead for improving early diagnosis of Alzheimer's disease. It will also be important to investigate what causes these specific proteins to change as Alzheimer's develops." The study was published in the February 2012 edition of the Journal of Alzheimer's Disease.

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