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Reference measurement procedure for CSF amyloid beta (Aβ) 1–42 and the CSF Aβ 1–42 /Aβ 1–40 ratio – a cross‐validation study against amyloid PET
Author(s) -
Pannee Josef,
Portelius Erik,
Minthon Lennart,
Gobom Johan,
Andreasson Ulf,
Zetterberg Henrik,
Hansson Oskar,
Blennow Kaj
Publication year - 2016
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.13838
Subject(s) - cerebrospinal fluid , concordance , receiver operating characteristic , lumbar puncture , alzheimer's disease , nuclear medicine , medicine , positron emission tomography , amyloid (mycology) , biomarker , dementia , area under the curve , pathology , chemistry , disease , biochemistry
A clinical diagnosis of Alzheimer's disease is currently made on the basis of results from cognitive tests in combination with medical history and general clinical evaluation, but the peptide amyloid‐beta (Aβ) in cerebrospinal fluid ( CSF ) is increasingly used as a biomarker for amyloid pathology in clinical trials and in recently proposed revised clinical criteria for Alzheimer's disease. Recent analytical developments have resulted in mass spectrometry ( MS ) reference measurement procedures for absolute quantification of Aβ 1–42 in CSF . The CSF Aβ 1–42 /Aβ 1–40 ratio has been suggested to improve the detection of cerebral amyloid deposition, by compensating for inter‐individual variations in total Aβ production. Our aim was to cross‐validate the reference measurement procedure as well as the Aβ 1–42 /Aβ 1–40 and Aβ 1–42 /Aβ 1–38 ratios in CSF , measured by high‐resolution MS , with the cortical level of Aβ fibrils as measured by amyloid ( 18 F‐flutemetamol) positron emission tomography ( PET ). We included 100 non‐demented patients with cognitive symptoms from the Swedish Bio FINDER study, all of whom had undergone both lumbar puncture and 18 F‐flutemetamol PET . Comparing CSF Aβ 1–42 concentrations with 18 F‐flutemetamol PET showed high concordance with an area under the receiver operating characteristic curve of 0.85 and a sensitivity and specificity of 82% and 81%, respectively. The ratio of Aβ 1–42 /Aβ 1–40 or Aβ 1–42 /Aβ 1–38 significantly improved concordance with an area under the receiver operating characteristic curve of 0.95 and a sensitivity and specificity of 96% and 91%, respectively. These results show that the CSF Aβ 1–42 /Aβ 1–40 and Aβ 1–42 /Aβ 1–38 ratios using the described MS method are strongly associated with cortical Aβ fibrils measured by 18 F‐flutemetamol PET .