Characterization of Tau in Cerebrospinal Fluid Using Mass Spectrometry

• Published in: Journal of proteome research Vol. 7; no. 5; pp. 2114 - 2120
• Main Authors: Portelius, Erik, Hansson, Sara F, Tran, Ai Jun, Zetterberg, Henrik, Grognet, Pierre, Vanmechelen, Eugeen, Höglund, Kina, Brinkmalm, Gunnar, Westman-Brinkmalm, Ann, Nordhoff, Eckhard, Blennow, Kaj, Gobom, Johan
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 01.05.2008
• Subjects: Alzheimer Disease; Alzheimer Disease - metabolism; Amino Acid Sequence; Brain Chemistry; cerebrospinal fluid; chemistry; Chromatography; Chromatography, Liquid - methods; genetics; Humans; Immunoprecipitation; Immunoprecipitation - methods; Liquid; Mass Spectrometry; Mass Spectrometry - methods; MEDICAL AND HEALTH SCIENCES; MEDICIN OCH HÄLSOVETENSKAP; metabolism; methods; Molecular Sequence Data; Peptide Fragments; Peptide Fragments - cerebrospinal fluid; Peptide Fragments - chemistry; Protein Isoforms; Protein Isoforms - cerebrospinal fluid; Protein Isoforms - chemistry; Protein Isoforms - genetics; tau Proteins; tau Proteins - cerebrospinal fluid; tau Proteins - chemistry; tau Proteins - genetics; MALDI-TOF MS; LC-MS/MS; Tau; Alzheimer’s disease; immunoprecipitation; cerebrospinal fluid
• ISSN: 1535-3893; 1535-3907
• DOI: 10.1021/pr7008669

The neurodegenerative disorder Alzheimer’s disease (AD) is the most common cause of dementia in the elderly. The presence of neurofibrillary tangles, consisting of hyperphosphorylated tau protein, is one of the major neuropathologic characteristics of the disease, making this protein an attractive biomarker for AD and a possible target for therapy. Here, we describe an optimized immunoprecipitation mass spectrometry method that enables, for the first time, detailed characterization of tau in human cerebrospinal fluid. The identities of putative tau fragments were confirmed using nanoflow liquid chromatography and tandem mass spectrometry. Nineteen tryptic fragments of tau were detected, of which 16 are found in all tau isoforms while 3 represented unique tau isoforms. These results pave the way for clinical CSF studies on the tauopathies.