Cerebrospinal Fluid β-Amyloid1–42 Levels in the Differential Diagnosis of Alzheimer’s Disease—Systematic Review and Meta-Analysis

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.

Prostaglandin I 2 upregulates the expression of anterior pharynx‐defective‐1α and anterior pharynx‐defective‐1β in amyloid precursor protein/presenilin 1 transgenic mice

“…These observations clearly indicate the possible role of CSF‐bound Aβ of APP/PS1 mice in upregulating the expression of APH‐1α/1β. However, previous studies have suggested that the CSF‐bound Aβ 1–42 level progressively reduced in patients with AD (Mo et al ., 2015). These observations indicate that the total level of Aβ 1–42 in the CSF of APP/PS1 mice might not be critical for upregulating the expression of APH‐1α/1β.…”

Alzheimer’s Amyloid-β is an Antimicrobial Peptide: A Review of the Evidence

“…The sequence of Ab is highly conserved in the AbPP orthologs of more than 70% of vertebrate species, in addition to many invertebrates [26][27][28]. In cognitively normal humans, Ab is present in the brain throughout life, as well as in the cerebrospinal fluid (CSF) and blood plasma [29][30][31]. Naked mole rats (Heterocephalus glaber) are the longest-lived rodent species, yet their brains naturally possess very high concentrations of soluble Ab, comparable to those found in the 3xTg-AD mouse model of AD [32].…”

Immunotherapeutic Approaches Targeting Amyloid-β, α-Synuclein, and Tau for the Treatment of Neurodegenerative Disorders

“…Many neurodegenerative diseases have similar symptoms as they result from the aggregation of the same protein(s), making diagnosis challenging at times [2]. Using the antibodies developed against specific conformations of these proteins as diagnostic tools would allow the clinician to make accurate decisions about which therapy to prescribe [170][171][172], greatly benefiting the therapeutic regimen and truly opening the door for personalized medicine. Moreover, it will probably be the case in the future that several immunotherapeutic options will be available for each disease, so therapy customization will become crucial.…”