title: Cerebrospinal Aβ11-x and 17-x levels as indicators of mild cognitive impairment and patients' stratification in Alzheimer's disease.
abstract: In the present work, the concentrations of Aβ11-x and Aβ17-x peptides (x=40 or 42), which result from the combined cleavages of β-amyloid precursor protein (AβPP) by β'/α or α/γ-secretases, respectively, were assessed in cerebrospinal fluid (CSF) samples from patients with Alzheimer's disease (AD) or mild cognitive impairment (MCI). Specific multiplexed assays were set up using new anti-40 and anti-42 monoclonal antibodies (mAbs) for the capture of these N-truncated Aβ peptides and anti-11 or anti-17 mAbs for their detection. The specificity, sensitivity and reproducibility of such assays were assessed using synthetic peptides and human cell models. Aβ11-x and Aβ17-x were then measured in CSF samples from patients with AD (n=23), MCI (n=23) and controls with normal cognition (n=21). Aβ11-x levels were significantly lower in patients with MCI than in controls. Compared with the combined quantification of Aβ1-42, total Tau (T-Tau) and phosphorylated Tau (P-Tau; AlzBio3, Innogenetics), the association of Aβ11-40, Aβ17-40 and T-Tau improved the discrimination between MCI and controls. Furthermore, when patients with MCI were classified into two subgroups (MCI ≤1.5 or ≥2 based on their CDR-SB (Cognitive Dementia Rating-Sum of Boxes) score), the CSF Aβ17-40/Aβ11-40 ratio was significantly higher in patients with CDR-SB ≤1.5 than in controls, whereas neither Aβ1-42, T-Tau nor P-Tau allowed the detection of this subpopulation. These results need to be confirmed in a larger clinical prospective cohort.
authors.affiliation: SysDiag CNRS/Bio-Rad UMR3145, Montpellier, France. jean-daniel.abraham@sysdiag.cnrs.fr
authors.forename: J-D
authors.initials: JD
authors.lastname: Abraham
authors.forename: S
authors.initials: S
authors.lastname: Promé
authors.forename: N
authors.initials: N
authors.lastname: Salvetat
authors.forename: L
authors.initials: L
authors.lastname: Rubrecht
authors.forename: S
authors.initials: S
authors.lastname: Cobo
authors.forename: E
authors.initials: E
authors.lastname: du Paty
authors.forename: P
authors.initials: P
authors.lastname: Galéa
authors.forename: E
authors.initials: E
authors.lastname: Mathieu-Dupas
authors.forename: S
authors.initials: S
authors.lastname: Ranaldi
authors.forename: C
authors.initials: C
authors.lastname: Caillava
authors.forename: G-A
authors.initials: GA
authors.lastname: Crémer
authors.forename: F
authors.initials: F
authors.lastname: Rieunier
authors.forename: P
authors.initials: P
authors.lastname: Robert
authors.forename: F
authors.initials: F
authors.lastname: Molina
authors.forename: D
authors.initials: D
authors.lastname: Laune
authors.forename: F
authors.initials: F
authors.lastname: Checler
authors.forename: J
authors.initials: J
authors.lastname: Fareh
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D016022:Case-Control Studies; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid* / Q000175:diagnosis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D012720:Severity of Illness Index
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments