Amyloid-β PET—Correlation with cerebrospinal fluid biomarkers and prediction of Alzheimer´s disease diagnosis in a memory clinic

• Published in: PloS one Vol. 14; no. 8; p. e0221365
• Main Authors: Müller, Ebba Gløersen, Edwin, Trine Holt, Stokke, Caroline, Navelsaker, Sigrid Stensby, Babovic, Almira, Bogdanovic, Nenad, Knapskog, Anne Brita, Revheim, Mona Elisabeth
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 2019; PLOS; Public Library of Science (PLoS)
• Subjects: Aged; Alzheimer Disease - cerebrospinal fluid; Alzheimer Disease - diagnosis; Alzheimer's disease; Amyloid; Amyloid beta-Peptides - cerebrospinal fluid; Aniline Compounds - administration & dosage; Benzothiazoles - administration & dosage; Bioindicators; Biology and Life Sciences; Biomarkers; Biomarkers - cerebrospinal fluid; Brain - diagnostic imaging; Brain research; Cerebrospinal fluid; Classification; Clinical medicine; Consent; Correlation; Correlation analysis; Cross-Sectional Studies; Dementia; Diagnosis; Drug dosages; Female; Fluorine isotopes; Geriatrics; Hospitals; Humans; Imaging, Three-Dimensional - methods; Male; Medical diagnosis; Medical imaging; Medicine and Health Sciences; Memory; Mental Health Services; Mental Status and Dementia Tests; Middle Aged; Neurology; Neuropathology; Neurosciences; NMR; Nuclear magnetic resonance; Nuclear medicine; Patients; People and Places; Peptide Fragments - cerebrospinal fluid; Physical Sciences; Positron emission; Positron emission tomography; Positron-Emission Tomography - methods; Radiopharmaceuticals - administration & dosage; Regression analysis; Research and Analysis Methods; Sensitivity; Tau protein; Tomography; Values; Norway
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0221365

Alzheimer's disease (AD) remains a clinical diagnosis but biomarkers from cerebrospinal fluid (CSF) and more lately amyloid imaging with positron emission tomography (PET), are important to support a diagnosis of AD. To compare amyloid-β (Aβ) PET imaging with biomarkers in CSF and evaluate the prediction of Aβ PET on diagnosis in a memory clinic setting. We included 64 patients who had lumbar puncture and Aβ PET with 18F-Flutemetamol performed within 190 days. PET was binary classified (Flut+ or Flut-) and logistic regression analyses for correlation to each CSF biomarker; Aβ 42 (Aβ42), total tau (T-tau) and phosphorylated tau (P-tau), were performed. Cut-off values were assessed by receiver operating characteristic (ROC) curves. Logistic regression was performed for prediction of clinical AD diagnosis. We assessed the interrater agreement of PET classification as well as for diagnoses, which were made both with and without knowledge of PET results. Thirty-two of the 34 patients (94%) in the Flut+ group and nine of the 30 patients (30%) in the Flut- group had a clinical AD diagnosis. There were significant differences in all CSF biomarkers in the Flut+ and Flut- groups. Aβ42 showed the highest correlation with 18F-Flutemetamol PET with a cut-off value of 706.5 pg/mL, corresponding to sensitivity of 88% and specificity of 87%. 18F-Flutemetamol PET was the best predictor of a clinical AD diagnosis. We found a very high interrater agreement for both PET classification and diagnosis. The present study showed an excellent correlation of Aβ42 in CSF and 18F-Flutemetamol PET and the presented cut-off value for Aβ42 yields high sensitivity and specificity for 18F-Flutemetamol PET. 18F-Flutemetamol PET was the best predictor of clinical AD diagnosis.