title: Amyloid beta peptide ratio 42/40 but not A beta 42 correlates with phospho-Tau in patients with low- and high-CSF A beta 40 load.
abstract: Neurochemical dementia diagnostics (NDD) can significantly improve the clinically based categorization of patients with early dementia disorders, and the cerebrospinal fluid (CSF) concentrations of amyloid beta peptides ending at the amino acid position of 42 (A beta x-42 and A beta 1-42) are widely accepted biomarkers of Alzheimer's disease (AD). However, in subjects with constitutively high- or low-CSF concentrations of total A beta peptides (tA beta), the NDD interpretation might lead to erroneous conclusions as these biomarkers seem to correlate better with the total A beta load than with the pathological status of a given patient in such cases. In this multicenter study, we found significantly increased CSF concentrations of phosphorylated Tau (pTau181) and total Tau in the group of subjects with high CSF A beta x-40 concentrations and decreased A beta x-42/x-40 concentration ratio compared with the group of subjects with low CSF A beta x-40 and normal A beta ratio (p<0.001 in both cases). Furthermore, we observed significantly decreased A beta ratio (p<0.01) in the group of subjects with APOE epsilon 4 allele compared with the group of subjects without this allele. Surprisingly, patients with low-A beta x-40 and the decreased A beta ratio characterized with decreased pTau181 (p<0.05), and unaltered total Tau compared with the subjects with high A beta x-40 and the A beta ratio in the normal range. We conclude that the amyloid beta concentration ratio should replace the 'raw' concentrations of corresponding A beta peptides to improve reliability of the neurochemical dementia diagnosis.
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Erlangen-Nuremberg, Erlangen, Germany. jens.wiltfang@psych.imed.uni-erlangen.de
authors.forename: Jens
authors.initials: J
authors.lastname: Wiltfang
authors.forename: Hermann
authors.initials: H
authors.lastname: Esselmann
authors.forename: Mirko
authors.initials: M
authors.lastname: Bibl
authors.forename: Michael
authors.initials: M
authors.lastname: Hüll
authors.forename: Harald
authors.initials: H
authors.lastname: Hampel
authors.forename: Holger
authors.initials: H
authors.lastname: Kessler
authors.forename: Lutz
authors.initials: L
authors.lastname: Frölich
authors.forename: Johannes
authors.initials: J
authors.lastname: Schröder
authors.forename: Oliver
authors.initials: O
authors.lastname: Peters
authors.forename: Frank
authors.initials: F
authors.lastname: Jessen
authors.forename: Christian
authors.initials: C
authors.lastname: Luckhaus
authors.forename: Robert
authors.initials: R
authors.lastname: Perneczky
authors.forename: Holger
authors.initials: H
authors.lastname: Jahn
authors.forename: Magdalena
authors.initials: M
authors.lastname: Fiszer
authors.forename: Juan Manuel
authors.initials: JM
authors.lastname: Maler
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Zimmermann
authors.forename: Ralf
authors.initials: R
authors.lastname: Bruckmoser
authors.forename: Johannes
authors.initials: J
authors.lastname: Kornhuber
authors.forename: Piotr
authors.initials: P
authors.lastname: Lewczuk
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000235:genetics; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D001057:Apolipoproteins E / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D013223:Statistics as Topic; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D016875:tau Proteins