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Centiloid cut-off values for optimal agreement between PET and CSF core AD biomarkers

Artikel i vetenskaplig tidskrift
Författare G. Salvado
J. L. Molinuevo
A. Brugulat-Serrat
C. Falcon
O. Grau-Rivera
M. Suarez-Calvet
J. Pavia
A. Ninerola-Baizan
A. Perissinotti
F. Lomena
C. Minguillon
K. Fauria
Henrik Zetterberg
Kaj Blennow
J. D. Gispert
J. Cami
R. Cacciaglia
M. Crous-Bou
C. Deulofeu
R. Dominguez
X. Gotsens
N. Gramunt
L. Hernandez
G. Huesa
J. Huguet
M. Leon
P. Marne
T. Menchon
M. Mila
G. Operto
M. Pascual
A. Polo
S. Pradas
A. Sala-Vila
G. Sanchez-Benavides
S. Segundo
A. Soteras
L. Tenas
M. Vilanova
N. Vilor-Tejedor
Publicerad i Alzheimers Research & Therapy
Volym 11
ISSN 1758-9193
Publiceringsår 2019
Publicerad vid Institutionen för neurovetenskap och fysiologi
Språk en
Länkar dx.doi.org/10.1186/s13195-019-0478-...
Ämnesord AD pathophysiology, Biomarker concordance, Threshold, Positivity, Preclinical, Early detection, Positron emission tomography, Phosphorylated tau, Biomarker categorization, preclinical alzheimers-disease, beta-amyloid 42, cerebrospinal-fluid, association, prevention, deposition, diagnosis, accuracy, Neurosciences & Neurology
Ämneskategorier Neurovetenskaper

Sammanfattning

BackgroundThe Centiloid scale has been developed to standardize measurements of amyloid PET imaging. Reference cut-off values of this continuous measurement enable the consistent operationalization of decision-making for multicentre research studies and clinical trials. In this study, we aimed at deriving reference Centiloid thresholds that maximize the agreement against core Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers in two large independent cohorts.MethodsA total of 516 participants of the ALFA+ Study (N=205) and ADNI (N=311) underwent amyloid PET imaging ([F-18]flutemetamol and [F-18]florbetapir, respectively) and core AD CSF biomarker determination using Elecsys (R) tests. Tracer uptake was quantified in Centiloid units (CL). Optimal Centiloid cut-offs were sought that maximize the agreement between PET and dichotomous determinations based on CSF levels of A(42), tTau, pTau, and their ratios, using pre-established reference cut-off values. To this end, a receiver operating characteristic analysis (ROC) was conducted, and Centiloid cut-offs were calculated as those that maximized the Youden's J Index or the overall percentage agreement recorded.ResultsAll Centiloid cut-offs fell within the range of 25-35, except for CSF A(42) that rendered an optimal cut-off value of 12 CL. As expected, the agreement of tau/A(42) ratios was higher than that of CSF A(42). Centiloid cut-off robustness was confirmed even when established in an independent cohort and against variations of CSF cut-offs.ConclusionsA cut-off of 12 CL matches previously reported values derived against postmortem measures of AD neuropathology. Together with these previous findings, our results flag two relevant inflection points that would serve as boundary of different stages of amyloid pathology: one around 12 CL that marks the transition from the absence of pathology to subtle pathology and another one around 30 CL indicating the presence of established pathology. The derivation of robust and generalizable cut-offs for core AD biomarkers requires cohorts with adequate representation of intermediate levels.Trial registrationALFA+ Study, NCT02485730ALFA PET Sub-study, NCT02685969

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