Palmqvist S et al JAMA Neurology. 2014
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 (Abeta) deposition. Objectives: To study whether CSF biomarkers, analyzed consecutively in routine clinical practice during 2 years, can predict cortical Abeta deposition and to establish a threshold for Abeta42 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 18F-flutemetamol. Main Outcomes and Measures: Analyses of CSF Abeta42, total tau, and phosphorylated tau using an enzyme-linked immunosorbent assay (INNOTEST) in clinical samples. Results: The agreement between Abeta classification with CSF Abeta42 and 18F-flutemetamol positron emission tomography was very high (kappa = 0.85). Of all the cases, 92% were classified identically using an Abeta42 cutoff of 647 pg/mL or less. Cerebrospinal fluid Abeta42 predicted abnormal cortical Abeta 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 Abeta42:tau or Abeta42:phosphorylated tau did not improve the prediction of Abeta deposition. Cerebrospinal fluid Abeta42 correlated significantly with Abeta deposition in all cortical regions. The highest correlations were in regions with high 18F-flutemetamol retention (eg, posterior cingulum and precuneus, r = -0.72). 18F-flutemetamol retention, but not CSF Abeta42, correlated significantly with global cognition (r = -0.32), memory function (r = -0.28), and hippocampal volume (r = -0.36) among those with abnormal Abeta deposition. Finally, the CSF Abeta42 cutoff derived from the original cohort (</=647 pg/mL) had an equally high agreement (95%; kappa = 0.89) with 18F-flutemetamol positron emission tomography in the validation cohort. Conclusions and Relevance: Cerebrospinal fluid Abeta42 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 Abeta deposition and so can be valuable for the early diagnosis of Alzheimer disease. Abnormal 18F-flutemetamol retention levels correlate with disease stage in patients with mild cognitive symptoms, but this is not the case for CSF Abeta42 measurements.