Cerebrospinal Fluid β-Amyloid(1–42) Levels in the Differential Diagnosis of Alzheimer’s Disease—Systematic Review and Meta-Analysis

OBJECTIVES: The purpose of this study was to carry out systematic review of the literature and meta-analysis to evaluate the diagnostic utility of cerebrospinal fluid (CSF) levels of the 42 amino acid form of amyloid-beta (Aβ(1–42)) as a biomarker for differentiating Alzheimer’s disease (AD) from non-AD dementia. METHODS: Design. Systematic literature review was used to evaluate the effectiveness of the Aβ for the diagnosis of AD. The Scottish Intercollegiate Guidelines Network (SIGN) tool was used to evaluate independently the quality of the studies. Data sources. The literature review covered from January 1, 2004, to October 22, 2013, and searched eight domestic databases including Korea Med and international databases including Ovid-MEDLINE, EMBASE, and Cochrane Library. Data Extraction and Synthesis. Primary criteria for inclusion were valid studies on (i) patients with mild cognitive impairment with confirmed or suspected AD and non-AD dementia, and (ii) assessment of Aβ(1–42) levels using appropriate comparative tests. RESULTS: A total of 17 diagnostic evaluation studies were identified in which levels of CSF Aβ(1–42) were assessed. Meta-analysis was performed on 11 robust studies that compared confirmed AD (n = 2211) with healthy individuals (n = 1030), 10 studies that compared AD with non-AD dementias (n = 627), and 5 studies that compared amnestic mild cognitive impairment (n = 1133) with non-amnestic type subjects (n = 1276). Overall, the CSF Aβ(1–42) levels were reduced in AD compared to controls or non-AD dementia. The effectiveness of test was evaluated for diagnostic accuracy (pooled sensitivity, 0.80 (95% CI 0.78–0.82); pooled specificity, 0.76 (95% CI 0.74–0.78). CONCLUSIONS: Reduced CSF Aβ(1–42) levels are of potential utility in the differential diagnosis of AD versus non-AD dementias and controls. Diagnostic accuracy was high in AD versus healthy controls. However, differential diagnosis for MCI or non-AD might be evaluated by other biomarkers.