Characterization of tau in cerebrospinal fluid using mass spectrometry.
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.
Portelius
Erik
E
Clinical Neurochemistry Laboratory, Department of Neuroscience and Physiology, University of Göteborg, Sahlgrenska University Hospital, S-431 80 Mölndal, Sweden. erik.portelius@neuro.gu.se
Hansson
Sara F
SF
Tran
Ai Jun
AJ
Zetterberg
Henrik
H
Grognet
Pierre
P
Vanmechelen
Eugeen
E
Höglund
Kina
K
Brinkmalm
Gunnar
G
Westman-Brinkmalm
Ann
A
Nordhoff
Eckhard
E
Blennow
Kaj
K
Gobom
Johan
J
D000544:Alzheimer Disease / Q000378:metabolism; D000595:Amino Acid Sequence; D001923:Brain Chemistry; D002853:Chromatography, Liquid / Q000379:methods; D006801:Humans; D047468:Immunoprecipitation / Q000379:methods*; D013058:Mass Spectrometry / Q000379:methods*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000134:cerebrospinal fluid / Q000737:chemistry; D020033:Protein Isoforms / Q000134:cerebrospinal fluid* / Q000737:chemistry* / Q000235:genetics; D016875:tau Proteins / Q000134:cerebrospinal fluid* / Q000737:chemistry* / Q000235:genetics
D010446:Peptide Fragments; D020033:Protein Isoforms; D016875:tau Proteins