title: Quantification of tau phosphorylated at threonine 181 in human cerebrospinal fluid: a sandwich ELISA with a synthetic phosphopeptide for standardization.
abstract: Hyperphosphorylation of the microtubule-associated protein tau is specifically found in those brain cells affected in several tauopathies. Tau has also been consistently found to be present in the cerebrospinal fluid (CSF). Here we report the quantification in CSF of tau phosphorylated at Thr 181 using an immunoassay with a synthetic peptide for standardization. The choice of the peptide was based on fine mapping of a phospho-dependent antibody, AT270 (P(176)PAPKT(p)P(132))and a human specific tau antibody, HT7 (P(159)PGQK(163)). CSF-phospho-tau levels were increased in Alzheimer patients (23.5+/-10.1 pM, P<0.01) compared with age-matched controls (15.9+/-5.7 pM), while decreased in patients with frontotemporal dementia (8.6+/-3.9 pM; P<0.01). In every diagnostic group, a highly significant correlation was found between total tau and phospho-tau (Alzheimer's disease, r(2)=0.73; frontotemporal dementia, r(2)=0.43; Control, r(2)=0.42), suggesting that the degree of phosphorylation of CSF-tau changes in different clinical conditions.
authors.affiliation: Innogenetics NV, Industriepark Zwijnaarde 7, Box 4, B-9052, Gent, Belgium. eugeevme@innogenetics.be
authors.forename: E
authors.initials: E
authors.lastname: Vanmechelen
authors.forename: H
authors.initials: H
authors.lastname: Vanderstichele
authors.forename: P
authors.initials: P
authors.lastname: Davidsson
authors.forename: E
authors.initials: E
authors.lastname: Van Kerschaver
authors.forename: B
authors.initials: B
authors.lastname: Van Der Perre
authors.forename: M
authors.initials: M
authors.lastname: Sjögren
authors.forename: N
authors.initials: N
authors.lastname: Andreasen
authors.forename: K
authors.initials: K
authors.lastname: Blennow
mesh_terms: D000595:Amino Acid Sequence; D015415:Biomarkers; D001923:Brain Chemistry; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods / Q000592:standards; D006801:Humans; D008969:Molecular Sequence Data; D010748:Phosphopeptides / Q000138:chemical synthesis / Q000378:metabolism*; D010766:Phosphorylation; D012015:Reference Standards; D013912:Threonine / Q000378:metabolism*; D016875:tau Proteins / Q000134:cerebrospinal fluid* / Q000378:metabolism
chemical_list: D015415:Biomarkers; D010748:Phosphopeptides; D016875:tau Proteins; D013912:Threonine