Agreement between ¹⁸F-Florbetapir PET imaging and cerebrospinal fluid Aβ1-42, Aβ1-40, tTau and pTau measured on the LUMIPULSE G fully automated platform

Abstract

INTRODUCTION: The development of fully automated immunoassay platforms has improved the technical reliability of cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease. METHODS:We quantified Aβ1-42, Aβ1-40, tTau and pTau levels using the Lumipulse G System in 94 CSF samples from participants of the SPIN cohort with available 18 F-Florbetapir imaging. Amyloid scans were assessed visually and through automated quantification. We determined the cutoffs of CSF biomarkers that optimized their agreement with 18 F-Florbetapir PET and evaluated concordance between markers of the amyloid category.RESULTS: Aβ1-42, tTau and pTau (but not Aβ1-40) and the ratios with Aβ1-42 had good diagnostic agreement with 18 F-Florbetapir PET. As a marker of amyloid pathology, the Aβ1-42/Aβ1-40 ratio had higher agreement and better correlation with amyloid PET than Aβ1-42 alone.DISCUSSION: CSF biomarkers measured with the Lumipulse G System show good agreement with amyloid imaging. Combination of Aβ1-42 with Aβ1-40 increases the agreement between markers of amyloid pathology.

Cerebrospinal fluid profile of NPTX2 supports role of Alzheimer’s disease-related inhibitory circuit dysfunction in adults with Down syndrome

“…All cognitive measures were lower in sAD compared to controls (all adj.p < 0.0001) and in dDS compared to aDS (all adj.p < 0.0001). CSF biomarker levels were as previously reported [17]. Briefly, compared to controls mean Aβ 1-42 levels were lower in all groups (all adj.p < 0.0001) and p-tau and t-tau levels were higher in sAD, pDS and dDS (all adj.p < 0.0001).…”

“…Controls and sporadic AD patients were retrospectively selected from the Sant Pau Initiative for Neurodegeneration (SPIN) cohort (Memory Unit, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain, [16]). Controls were without cognitive or neurological disorders and normal levels of core AD CSF biomarkers (Aβ 1-42 , t-tau and p-tau), determined according to our internal cut-offs [17]. AD patients were clinically diagnosed with dementia due to AD [18].…”

“…Adults with DS were recruited from the Down Alzheimer Barcelona Neuroimaging Initiative, a prospective longitudinal cohort, linked to a population-based health plan in Catalonia, Spain, led by the Catalan Foundation for Down Syndrome and Hospital de la Santa Creu i Sant Pau, Barcelona, Spain [19]. Inclusion criteria for participation in the study required that participants were over 18 years of age, that they received a comprehensive neurological and neuropsychological evaluation and underwent a lumbar puncture to assess AD biomarkers levels (CSF Aβ 1-42 , t-tau and p-tau) [17]. As in previous studies [19][20][21], participants with DS were classified by neurologists and neuropsychologists, masked to biomarker data in a consensus meeting into the following groups: asymptomatic AD (aDS; no clinical or neuropsychological suspicion of symptomatic AD), prodromal AD (pDS; suspicion of cognitive decline due to AD, but symptoms did not fulfill criteria for dementia) and AD dementia (dDS; full blown dementia).…”

“…Samples had been previously stored at − 80°C and had not been thawed prior to analysis. Commercially available automated immunoassays were used to determine levels of CSF Aβ 1-42 (Lumipulse Aβ 1-42 , Fujirebio-Europe, Belgium) total tau (Lumipulse G Total Tau, Fujirebio-Europe) and tau phosphorylated at threonine residue 181 (Lumipulse G PTAU 181, Fujirebio-Europe) in the DABNI cohort and SPIN controls [17]. An in-house enzyme-linked immunosorbent assay targeting the N-terminal fragment encoding amino acid 1 to 201 of NPTX2 was performed in the Baltimore Laboratory as previously described [12].…”