A Systematic Review and Meta-Analysis of Cerebrospinal Fluid Amyloid and Tau Levels Identifies Mild Cognitive Impairment Patients Progressing to Alzheimer’s Disease

Reported levels of amyloid-beta and tau in human cerebrospinal fluid (CSF) were evaluated to discover if these biochemical markers can predict the transition from Mild Cognitive Impairment (MCI) to Alzheimer’s disease (AD). A systematic review of the literature in PubMed and Web of Science (April 20...

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Main Authors: Yunxing Ma, Julia Brettschneider, Joanna F. Collingwood
Format: Article
Language:English
Published: MDPI AG 2022-07-01
Series:Biomedicines
Subjects:
Online Access:https://www.mdpi.com/2227-9059/10/7/1713
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author Yunxing Ma
Julia Brettschneider
Joanna F. Collingwood
author_facet Yunxing Ma
Julia Brettschneider
Joanna F. Collingwood
author_sort Yunxing Ma
collection DOAJ
description Reported levels of amyloid-beta and tau in human cerebrospinal fluid (CSF) were evaluated to discover if these biochemical markers can predict the transition from Mild Cognitive Impairment (MCI) to Alzheimer’s disease (AD). A systematic review of the literature in PubMed and Web of Science (April 2021) was performed by a single researcher to identify studies reporting immunologically-based (xMAP or ELISA) measures of CSF analytes Aβ(1-42) and/or P-tau and/or T-tau in clinical studies with at least two timepoints and a statement of diagnostic criteria. Of 1137 screened publications, 22 met the inclusion criteria for CSF Aβ(1-42) measures, 20 studies included T-tau, and 17 included P-tau. Six meta-analyses were conducted to compare the analytes for healthy controls (HC) versus progressive MCI (MCI_AD) and for non-progressive MCI (Stable_MCI) versus MCI_AD; effect sizes were determined using random effects models. The heterogeneity of effect sizes across studies was confirmed with very high significance (<i>p</i> < 0.0001) for all meta-analyses except HC versus MCI_AD T-tau (<i>p</i> < 0.05) and P-tau (non-significant). Standard mean difference (SMD) was highly significant (<i>p</i> < 0.0001) for all comparisons (Stable_MCI versus MCI_AD: SMD [95%-CI] Aβ(1-42) = 1.19 [0.96,1.42]; T-tau = −1.03 [−1.24,−0.82]; P-tau = −1.03 [−1.47,−0.59]; HC versus MCI_AD: SMD Aβ(1-42) = 1.73 [1.39,2.07]; T-tau = −1.13 [−1.33,−0.93]; P-tau = −1.10 [−1.23,−0.96]). The follow-up interval in longitudinal evaluations was a critical factor in clinical study design, and the Aβ(1–42)/P-tau ratio most robustly differentiated progressive from non-progressive MCI. The value of amyloid-beta and tau as markers of patient outcome are supported by these findings.
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spelling doaj.art-66d440eaa6354ba393452c851ddb7eb82023-12-03T14:42:40ZengMDPI AGBiomedicines2227-90592022-07-01107171310.3390/biomedicines10071713A Systematic Review and Meta-Analysis of Cerebrospinal Fluid Amyloid and Tau Levels Identifies Mild Cognitive Impairment Patients Progressing to Alzheimer’s DiseaseYunxing Ma0Julia Brettschneider1Joanna F. Collingwood2School of Engineering, University of Warwick, Coventry CV4 7AL, UKDepartment of Statistics, University of Warwick, Coventry CV4 7AL, UKSchool of Engineering, University of Warwick, Coventry CV4 7AL, UKReported levels of amyloid-beta and tau in human cerebrospinal fluid (CSF) were evaluated to discover if these biochemical markers can predict the transition from Mild Cognitive Impairment (MCI) to Alzheimer’s disease (AD). A systematic review of the literature in PubMed and Web of Science (April 2021) was performed by a single researcher to identify studies reporting immunologically-based (xMAP or ELISA) measures of CSF analytes Aβ(1-42) and/or P-tau and/or T-tau in clinical studies with at least two timepoints and a statement of diagnostic criteria. Of 1137 screened publications, 22 met the inclusion criteria for CSF Aβ(1-42) measures, 20 studies included T-tau, and 17 included P-tau. Six meta-analyses were conducted to compare the analytes for healthy controls (HC) versus progressive MCI (MCI_AD) and for non-progressive MCI (Stable_MCI) versus MCI_AD; effect sizes were determined using random effects models. The heterogeneity of effect sizes across studies was confirmed with very high significance (<i>p</i> < 0.0001) for all meta-analyses except HC versus MCI_AD T-tau (<i>p</i> < 0.05) and P-tau (non-significant). Standard mean difference (SMD) was highly significant (<i>p</i> < 0.0001) for all comparisons (Stable_MCI versus MCI_AD: SMD [95%-CI] Aβ(1-42) = 1.19 [0.96,1.42]; T-tau = −1.03 [−1.24,−0.82]; P-tau = −1.03 [−1.47,−0.59]; HC versus MCI_AD: SMD Aβ(1-42) = 1.73 [1.39,2.07]; T-tau = −1.13 [−1.33,−0.93]; P-tau = −1.10 [−1.23,−0.96]). The follow-up interval in longitudinal evaluations was a critical factor in clinical study design, and the Aβ(1–42)/P-tau ratio most robustly differentiated progressive from non-progressive MCI. The value of amyloid-beta and tau as markers of patient outcome are supported by these findings.https://www.mdpi.com/2227-9059/10/7/1713Alzheimer’s diseasecerebrospinal fluidtauamyloid betamild cognitive impairmentbiomarker
spellingShingle Yunxing Ma
Julia Brettschneider
Joanna F. Collingwood
A Systematic Review and Meta-Analysis of Cerebrospinal Fluid Amyloid and Tau Levels Identifies Mild Cognitive Impairment Patients Progressing to Alzheimer’s Disease
Biomedicines
Alzheimer’s disease
cerebrospinal fluid
tau
amyloid beta
mild cognitive impairment
biomarker
title A Systematic Review and Meta-Analysis of Cerebrospinal Fluid Amyloid and Tau Levels Identifies Mild Cognitive Impairment Patients Progressing to Alzheimer’s Disease
title_full A Systematic Review and Meta-Analysis of Cerebrospinal Fluid Amyloid and Tau Levels Identifies Mild Cognitive Impairment Patients Progressing to Alzheimer’s Disease
title_fullStr A Systematic Review and Meta-Analysis of Cerebrospinal Fluid Amyloid and Tau Levels Identifies Mild Cognitive Impairment Patients Progressing to Alzheimer’s Disease
title_full_unstemmed A Systematic Review and Meta-Analysis of Cerebrospinal Fluid Amyloid and Tau Levels Identifies Mild Cognitive Impairment Patients Progressing to Alzheimer’s Disease
title_short A Systematic Review and Meta-Analysis of Cerebrospinal Fluid Amyloid and Tau Levels Identifies Mild Cognitive Impairment Patients Progressing to Alzheimer’s Disease
title_sort systematic review and meta analysis of cerebrospinal fluid amyloid and tau levels identifies mild cognitive impairment patients progressing to alzheimer s disease
topic Alzheimer’s disease
cerebrospinal fluid
tau
amyloid beta
mild cognitive impairment
biomarker
url https://www.mdpi.com/2227-9059/10/7/1713
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