Volume 15, Issue 7, Pages 673-684 (June 2016) CSF and blood biomarkers for the diagnosis of Alzheimer's disease: a systematic review and meta-analysis  Dr Bob Olsson, PhD, Ronald Lautner, MD, Ulf Andreasson, PhD, Annika Öhrfelt, PhD, Erik Portelius, PhD, Maria Bjerke, PhD, Mikko Hölttä, PhD, Christoffer Rosén, MD, Caroline Olsson, PhD, Gabrielle Strobel, MSc, Elizabeth Wu, MLIS, Kelly Dakin, PhD, Prof Max Petzold, PhD, Prof Kaj Blennow, MD, Prof Henrik Zetterberg, MD  The Lancet Neurology  Volume 15, Issue 7, Pages 673-684 (June 2016) DOI: 10.1016/S1474-4422(16)00070-3 Copyright © 2016 Elsevier Ltd Terms and Conditions

Figure 1 Study selection The Lancet Neurology 2016 15, 673-684DOI: (10.1016/S1474-4422(16)00070-3) Copyright © 2016 Elsevier Ltd Terms and Conditions

Figure 2 Alzheimer's disease to control ratio for CSF T-tau CSF ratios of T-tau concentrations between patients with Alzheimer's disease and controls. Individual study ratios and their corresponding 95% CIs are indicated by filled squares. The size of the square indicates the weight of the study. The averaged ratio and 95% CI is indicated by a diamond. The solid line indicates a ratio of one and the dotted line indicates the average ratio. Arrowheads indicate values in excess of 5. *Number of patients or controls. The Lancet Neurology 2016 15, 673-684DOI: (10.1016/S1474-4422(16)00070-3) Copyright © 2016 Elsevier Ltd Terms and Conditions

Figure 3 Alzheimer's disease to control ratio for CSF P-tau CSF ratios of P-tau concentrations between patients with Alzheimer's disease and controls. Individual study ratios and their corresponding 95% CIs are indicated by filled squares. The size of the square indicates the weight of the study. The averaged ratio and 95% CI is indicated by a diamond. The solid line indicates a ratio of one and the dotted line indicates the average ratio. Arrowheads indicate values in excess of 5. *Number of patients or controls. The Lancet Neurology 2016 15, 673-684DOI: (10.1016/S1474-4422(16)00070-3) Copyright © 2016 Elsevier Ltd Terms and Conditions

Figure 4 Alzheimer's disease to control ratios for CSF Aβ42 CSF ratios of AB42 concentrations between patients with Alzheimer's disease and controls. Individual study ratios and their corresponding 95% CIs are indicated by filled squares. The size of the square indicates the weight of the study. The averaged ratio and 95% CI is indicated by a diamond. The solid line indicates a ratio of one and the dotted line indicates the average ratio. *Number of patients or controls. The Lancet Neurology 2016 15, 673-684DOI: (10.1016/S1474-4422(16)00070-3) Copyright © 2016 Elsevier Ltd Terms and Conditions

Figure 5 Alzheimer's disease to control ratio for CSF markers of neurodegeneration, glial activation, and blood–brain-barrier function CSF ratios of NFL (A), NSE (B), VLP-1 (C), HFABP (D), YKL-40 (E), GFAP (F), MCP-1 (G), and CSF to serum albumin ratio (H) between patients with Alzheimer's disease and controls. Individual study ratios and their corresponding 95% CIs are indicated by filled squares. The size of the square indicates the weight of the study. All average ratios and their corresponding 95% CIs are indicated by diamonds. Arrowheads indicate values in excess of 5. *Number of patients or controls. The Lancet Neurology 2016 15, 673-684DOI: (10.1016/S1474-4422(16)00070-3) Copyright © 2016 Elsevier Ltd Terms and Conditions

Figure 6 Biomarker performance rating in patients with Alzheimer's disease versus controls Head-to-head biomarker performance in CSF (A) and in serum and plasma (B) based on average Alzheimer's disease to control ratios. Biomarkers shown in green are significant with good effect sizes, in purple significant with moderate effect sizes, and in red non-significant or significant with minor effect sizes. The Alzheimer's disease to control ratios of CSF Aβ42, Aβ40, and Aβ38 were inverted to allow for a clear comparison with the other biomarkers. The Lancet Neurology 2016 15, 673-684DOI: (10.1016/S1474-4422(16)00070-3) Copyright © 2016 Elsevier Ltd Terms and Conditions