Abstract
ObjectivesThe 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 (Aβ1–42) 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 Aβ1–42 levels using appropriate comparative tests.ResultsA total of 17 diagnostic evaluation studies were identified in which levels of CSF Aβ1–42 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 Aβ1–42 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).ConclusionsReduced CSF Aβ1–42 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.
Highlights
A substantial proportion of current therapeutic development in Alzheimer’s disease (AD) focuses on therapies targeting the Aβ peptide or Aβ aggregates, the core pathology of AD [1,2]
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)
The cerebrospinal fluid (CSF) Aβ1–42 levels were reduced in AD compared to controls or non-AD dementia
Summary
A substantial proportion of current therapeutic development in AD focuses on therapies targeting the Aβ peptide or Aβ aggregates, the core pathology of AD [1,2]. Large-scale clinical trials of Aβ removal by immunological or pharmacologic means have yielded no reproducible benefits [2]. There are two routes to resolve this dilemma. A second strategy is to develop therapies that are likely to be of benefit in symptomatic patients (i.e., in a preclinical stage 3 or prodromal AD) [2]. Further development of AD therapeutics will require the establishment of biomarkers that accurately reflect the progression of AD pathology, thereby permitting early diagnosis of AD and facilitating drug trials selectively targeting the early predementia stages of the disease [3]
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