Olsson, B;
Lautner, R;
Andreasson, U;
Ohrfelt, A;
Portelius, E;
Bjerke, M;
Holtta, M;
... Zetterberg, H; + view all
(2016)
CSF and blood biomarkers for the diagnosis of Alzheimer's disease: a systematic review and meta-analysis.
The Lancet Neurology
, 15
(7)
pp. 673-684.
10.1016/s1474-4422(16)00070-3.
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Abstract
Background Alzheimer’s disease (AD) biomarkers are important for early diagnosis in clinical routine and trials. Three core AD cerebrospinal fluid (CSF) biomarkers (Aβ42, T-tau, and P-tau) have been evaluated in numerous studies and there are several emerging AD markers. However, there is no comprehensive meta-analysis of their diagnostic performance. Methods We screened PubMed and Web of Science for articles on CSF and blood biomarkers reflecting neurodegeneration (T-tau, NFL, NSE, VLP-1, and HFABP), amyloid precursor protein (APP) metabolism (Aβ42, Aβ40, Aβ38, sAPPα, and sAPPβ), tangle pathology (P-tau), blood-brain-barrier function (albumin ratio) and glial activation (YKL-40, MCP-1, and GFAP). Based on inclusion criteria, 231 of 13,319 screened articles were included. Biomarker performance was rated on fold change between AD and controls and between mild cognitive impairment (MCI) who later converted to AD (MCI-AD) and stable MCI who had at least a follow-up time of two years. Findings Core biomarkers differentiated AD from controls with excellent performance; CSF T-tau (2·54, CI 2·44-2·64, p<0·0001, 152 studies), P-tau (1·88, CI 1·79-1·97, p<0·0001, 91 studies), and Aβ42 (0·56, CI 0·55-0·58, p<0·0001, 131 studies). Differentiation between MCI-AD and stable MCI was also strong (0·66-1·81). Furthermore, CSF NFL (2·35, 95% CI 1·90-2·91, p<0·0001) and plasma T-tau (1·95, 95% CI 1·12-3·38, p=0·02) had large effect sizes, while CSF NSE, VLP-1, HFABP, and YKL-40 were more moderate (1·28-1·47). Remaining biomarkers had marginal effect sizes or were non-significant. Interpretation Core CSF AD biomarkers and NFL, as well as plasma T-tau, are strongly associated with AD. Emerging biomarkers CSF NSE, VLP-1, HFABP, and YKL-40 are moderately associated with AD, while plasma Aβ42 and Aβ40 are not.
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