Accuracy of Brain Amyloid Detection in Clinical Practice Using Cerebrospinal Fluid β-Amyloid 42 A Cross-Validation Study Against Amyloid Positron Emission Tomography

IMPORTANCE Before adding cerebrospinal fluid (CSF) biomarkers to the diagnostic workup of Alzheimer disease, it needs to be determined whether CSF biomarkers analyzed in routine clinical practice can reliably predict cortical beta-amyloid (A beta) deposition. OBJECTIVES To study whether CSF biomarkers, analyzed consecutively in routine clinical practice during 2 years, can predict cortical A beta deposition and to establish a threshold for A beta 42 abnormality. DESIGN, SETTING, AND PARTICIPANTS This cross-sectional study (The Swedish BioFINDER [Biomarkers For Identifying Neurodegenerative Disorders Early and Reliably] Study) was conducted at 3 memory clinics. It involved consecutively referred, nondemented patients with mild cognitive symptoms (original cohort, n = 118; validation cohort, n = 38). EXPOSURES Amyloid positron emission tomography imaging with F-18-flutemetamol. MAIN OUTCOMES AND MEASURES Analyses of CSF A beta 42, total tau, and phosphorylated tau using an enzyme-linked immunosorbent assay (INNOTEST) in clinical samples. RESULTS The agreement between A beta classification with CSF A beta 42 and 18F-flutemetamol positron emission tomography was very high (K = 0.85). Of all the cases, 92% were classified identically using an A beta 42 cutoff of 647 pg/mL or less. Cerebrospinal fluid A beta 42 predicted abnormal cortical A beta deposition accurately (odds ratio, 165; 95% CI, 39-693; area under the receiver operating characteristic curve, 0.94; 95% CI, 0.88-0.97). The association was independent of age, sex, APOE (apolipoprotein E) genotype, hippocampal volume, memory, and global cognition (adjusted odds ratio, 169; 95% CI, 25-1143). Using ratios of CSF A beta 42: tau or A beta 42: phosphorylated tau did not improve the prediction of A beta deposition. Cerebrospinal fluid A beta 42 correlated significantly with A beta deposition in all cortical regions. The highest correlations were in regions with high F-18-flutemetamol retention (eg, posterior cingulum and precuneus, r = -0.72). 18F-flutemetamol retention, but not CSF A beta 42, correlated significantly with global cognition (r = -0.32), memory function (r = -0.28), and hippocampal volume (r = -0.36) among those with abnormal A beta deposition. Finally, the CSF A beta 42 cutoff derived from the original cohort (<= 647pg/mL) had an equally high agreement (95%; K= 0.89) with F-18-flutemetamol positron emission tomography in the validation cohort. CONCLUSIONS AND RELEVANCE Cerebrospinal fluid A beta 42 analyzed consecutively in routine clinical practice at an accredited laboratory can be used with high accuracy to determine whether a patient has normal or increased cortical A beta deposition and so can be valuable for the early diagnosis of Alzheimer disease. Abnormal F-18-flutemetamol retention levels correlate with disease stage in patients with mild cognitive symptoms, but this is not the case for CSF A beta 42 measurements.