Cerebrospinal fluid ratio of phosphorylated tau protein and beta amyloid predicts amyloid PET positivity


Authors: J. Cerman 1,2;  J. Laczó 1,2;  M. Vyhnálek 1,2;  J. Malinovská 1;  J. Hanzalová 1;  J. Hort 1,2
Authors‘ workplace: Neurologická klinika 2. LF UK, a FN Motol, Praha 1;  Mezinárodní centrum klinického, výzkumu, FN u sv. Anny v Brně 2
Published in: Cesk Slov Neurol N 2020; 83(2): 173-179
Category: Original Paper
doi: 10.14735/amcsnn2020173

Současná diagnostická kritéria Alzheimerovy nemoci zdůrazňují vedle klinické diagnózy také vyšetření metabolických biomarkerů. V ČR je dostupné vyšetření pomocí amyloidové PET a vyšetření biomarkerů v likvoru (hladiny beta amyloidu Aβ 1-42, celkového tau a fosforylovaného tau 181). Cílem této studie bylo zhodnotit konkordanci amyloidové PET a biomarkerů v likvoru v klinických podmínkách a navrhnout způsob interpretace výsledků likvoru ke zlepšení predikce výsledku amyloidové PET především u rozporných případů.

Overview

Aim: Current diagnostic criteria for Alzheimer’s disease shift the focus from clinical findings to metabolic biomarkers. Most widely used metabolic biomarkers in the Czech Republic are cerebrospinal fluid levels of beta amyloid 1-42, total tau, and phosphorylated tau 181, as well as amyloid PET. Our aim was to investigate the concordance of amyloid PET and cerebrospinal fluid biomarkers in clinical settings and propose a way of interpreting cerebrospinal fluid biomarker results in order to better predict the amyloid PET status in contradictory cases.

Methods: A total of 103 patients underwent neuropsychological assessment, brain MRI, visually evaluated flutemetamol amyloid PET and examination of biomarkers in the cerebrospinal fluid. Concordance of amyloid PET and cerebrospinal fluid biomarkers was compared and subsequent optimal cut-off for the beta amyloid 1-42 and phosphorylated tau protein ratio was calculated.

Results: Concordance between amyloid PET and beta amyloid 1-42 was 79%, followed by phosphorylated tau protein (72%). In 40% of cases, the results of cerebrospinal fluid biomarkers was contradictory. Beta amyloid 1-42 and phosphorylated tau protein ratio was found to best discriminate between amyloid PET positive and negative patients (AUC = 0.938, 95% CI = 0.890–0.986; P < 0.001). Ratio of 9.47 provided 91.0% sensitivity and 91.3% specificity.

Conclusion: Both methods show good diagnostic concordance. In case of contradictory cerebrospinal fluid biomarkers, we encourage using the beta amyloid 1-42 and phosphorylated tau protein ratio.

The Editorial Board declares that the manuscript met the ICMJE “uniform requirements” for biomedical papers.

Keywords:

Alzheimer‘s disease – amyloid PET – biomarkers – cerebrospinal fluid – flutemetamol – beta amyloid Aβ 1-42 – tau protein


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Paediatric neurology Neurosurgery Neurology

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