Systematic Review and Meta-Analysis of Diagnostic Alzheimer’s Disease with Blood Biomarkers
Keywords:
Alzheimer’s disease, Blood biomarker, Phosphorylated tau, Diagnosis, Meta-AnalysisAbstract
Background: One of the world's leading causes of death is Alzheimer's disease (AD). Diagnostic of the disease and determining the risk before it reaches a severe stage are essential to reduce the rate of a patient’s development into the dementia phase, as well as locating practical, economical, and effective diagnostic tools, including blood tests, are easier and still reasonably priced, compared to neuroimaging or cerebrospinal fluid (CSF) examinations.
Method: The studies were systematically searched for and determined by pooled sensitivity and specificity which studies were about diagnosing AD using the single molecular array (SIMOA) method by detecting phosphorylated tau (p-tau) in the blood. In addition, Egger's test results for heterogeneity and publication bias were evaluated.
Result: After systematically review the studies from 2016 to 2023, seven studies have been included for the meta-analysis. The results show low level of heterogeneity (I2 = 28.99%) and no publication bias Egger's test in sensitivity and specificity (p-value = 0.244 and 0.084, respectively) in patients.
Conclusion: The ability to identify p-tau in blood with SIMOA has been useful in the diagnosis of Alzheimer's disease. Currently, this procedure is utilized in conjunction with other diagnostic approaches for diagnosis.
References
WHO reveals leading causes of death and disability worldwide: 2000-2019: World Health Organization; 2020 [updated 9 December 2020. Available from: https://www.who.int/news/item/09-12-2020-who-reveals-leading-causes-of-death-and-disability-worldwide-2000-2019.
Gustavsson A, Norton N, Fast T, Frölich L, Georges J, Holzapfel D, et al. Global estimates on the number of persons across the Alzheimer's disease continuum. Alzheimer's & Dementia. 2023; 19(2): 658-70. DOI: 10.1002/alz.12694
Khachaturian ZS. Diagnosis of Alzheimer's Disease. Archives of Neurology. 1985; 42(11): 1097-105.
Delaby C, Hirtz C, Lehmann S. Overview of the blood biomarkers in Alzheimer's disease: Promises and challenges. Revue Neurologique. 2023; 179(3): 161-72. DOI: 10.1016/j.neurol.2022.09.003
Karikari TK, Pascoal TA, Ashton NJ, Janelidze S, Benedet AL, Rodriguez JL, et al. Blood phosphorylated tau 181 as a biomarker for Alzheimer's disease: a diagnostic performance and prediction modelling study using data from four prospective cohorts. Lancet Neurol. 2020; 19(5): 422-33. DOI: 10.1016/S1474-4422(20)30071-5
Joyce RC, Nicholas JA, Thomas KK, Tomotaka T, Michael S, Henrik Z, et al. Blood-based high sensitivity measurements of beta-amyloid and phosphorylated tau as biomarkers of Alzheimer’s disease: a focused review on recent advances. Journal of Neurology, Neurosurgery & Psychiatry. 2021; 92(11): 1231. DOI: 10.1136/jnnp-2021-327370
Karikari TK, Ashton NJ, Brinkmalm G, Brum WS, Benedet AL, Montoliu-Gaya L, et al. Blood phospho-tau in Alzheimer disease: analysis, interpretation, and clinical utility. Nature Reviews Neurology. 2022; 18(7): 400-18. DOI: 10.1038/s41582-022-00665-2
Krishna G, Thangaraju Sivakumar P, Dahale AB, Subramanian S. Potential Utility of Plasma Biomarker Panels in Differential Diagnosis of Alzheimer's Disease. J Alzheimers Dis Rep. 2024; 8(1): 1-7. DOI: 10.3233/ADR-230156
Matthew JP, Joanne EM, Patrick MB, Isabelle B, Tammy CH, Cynthia DM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021; 372: n71. DOI: 10.1136/bmj.n71
Binney N, Hyde C, Bossuyt PM. On the Origin of Sensitivity and Specificity. Ann Intern Med. 2021; 174(3): 401-7. DOI: 10.7326/M20-5028
Nyaga VN, Arbyn M. Metadta: a Stata command for meta-analysis and meta-regression of diagnostic test accuracy data – a tutorial. Archives of Public Health. 2022; 80(1): 95. DOI: 10.1186/s13690-021-00747-5
Noma H. MVPBT: R package for publication bias tests in meta-analysis of diagnostic accuracy studies. arXiv preprint arXiv: 220907270. 2022. DOI: 10.48550/arXiv.2209.07270
Hong C, Salanti G, Morton SC, Riley RD, Chu H, Kimmel SE, et al. Testing small study effects in multivariate meta-analysis. Biometrics. 2020; 76(4): 1240-50. DOI: 10.1111/biom.13342
Chootrakool H, Shi JQ, Yue R. Meta-analysis and sensitivity analysis for multi-arm trials with selection bias. Stat Med. 2011; 30(11): 1183-98. DOI: 10.1002/sim.4143
Chootrakool H, Treewai P. Meta-Analysis of Multi-Arm Trials Using Binomial Approach. Open Journal of Statistics. 2022; 12: 15-32. DOI: 10.4236/ojs.2022.121002
Chootrakool H, Qing Shi J. Meta-analysis of multi-arm trials using empirical logistic transform. Open Med Inform J. 2008; 2: 112-6. DOI: 10.2174/1874431100802010112
Whiting PF, Rutjes AWS, Westwood ME, Mallett S, Deeks JJ, Reitsma JB, et al. QUADAS-2: A Revised Tool for the Quality Assessment of Diagnostic Accuracy Studies. Annals of Internal Medicine. 2011; 155(8): 529-36. DOI: 10.7326/0003-4819-155-8-201110180-00009
Baiardi S, Quadalti C, Mammana A, Dellavalle S, Zenesini C, Sambati L, et al. Diagnostic value of plasma p-tau181, NfL, and GFAP in a clinical setting cohort of prevalent neurodegenerative dementias. Alzheimer's Research & Therapy. 2022; 14(1): 153. DOI: 10.1186/s13195-022-01093-6
Smirnov DS, Ashton NJ, Blennow K, Zetterberg H, Simrén J, Lantero-Rodriguez J, et al. Plasma biomarkers for Alzheimer's Disease in relation to neuropathology and cognitive change. Acta Neuropathol. 2022; 143(4): 487-503. DOI: 10.1007/s00401-022-02408-5
Thijssen EH, Verberk IMW, Kindermans J, Abramian A, Vanbrabant J, Ball AJ, et al. Differential diagnostic performance of a panel of plasma biomarkers for different types of dementia. Alzheimers Dement (Amst). 2022; 14(1): e12285. DOI: 10.1002/dad2.12285
Oeckl P, Anderl-Straub S, Danek A, Diehl-Schmid J, Fassbender K, Fliessbach K, et al. Relationship of serum beta-synuclein with blood biomarkers and brain atrophy. Alzheimer's & Dementia. 2023; 19(4): 1358-71. DOI: 10.1002/alz.12790.
Chatterjee P, Pedrini S, Doecke JD, Thota R, Villemagne VL, Doré V, et al. Plasma Aβ42/40 ratio, p-tau181, GFAP, and NfL across the Alzheimer's disease continuum: A cross-sectional and longitudinal study in the AIBL cohort. Alzheimers Dement. 2023; 19(4): 1117-34. DOI: 10.1002/alz.12724
Bayoumy S, Verberk IMW, den Dulk B, Hussainali Z, Zwan M, van der Flier WM, et al. Clinical and analytical comparison of six Simoa assays for plasma P-tau isoforms P-tau181, P-tau217, and P-tau231. Alzheimers Res Ther. 2021; 13(1): 198. DOI: 10.1186/s13195-021-00939-9
Tatebe H, Kasai T, Ohmichi T, Kishi Y, Kakeya T, Waragai M, et al. Quantification of plasma phosphorylated tau to use as a biomarker for brain Alzheimer pathology: pilot case-control studies including patients with Alzheimer’s disease and down syndrome. Molecular Neurodegeneration. 2017; 12(1): 63. DOI: 10.1186/s13024-017-0206-8
Sarto J, Ruiz-García R, Guillén N, Ramos-Campoy Ó, Falgàs N, Esteller D, et al. Diagnostic Performance and Clinical Applicability of Blood-Based Biomarkers in a Prospective Memory Clinic Cohort. Neurology. 2023; 100(8): e860-e73. DOI: 10.1212/WNL.0000000000201597
Ding X, Zhang S, Jiang L, Wang L, Li T, Lei P. Ultrasensitive assays for detection of plasma tau and phosphorylated tau 181 in Alzheimer’s disease: a systematic review and meta-analysis. Translational Neurodegeneration. 2021; 10(1): 10. DOI: 10.3233/JAD-201499
Chen L, Niu X, Wang Y, Lv S, Zhou X, Yang Z, et al. Plasma tau proteins for the diagnosis of mild cognitive impairment and Alzheimer's disease: A systematic review and meta-analysis. Front Aging Neurosci. 2022; 14. DOI: 10.3389/fnagi.2022.942629
Koychev I, Jansen K, Dette A, Shi L, Holling H. Blood-Based ATN Biomarkers of Alzheimer's Disease: A Meta-Analysis. J Alzheimers Dis. 2021; 79(1): 177-95. DOI: 10.3233/JAD-200900
Wu L, Arvai S, Wang S-HJ, Liu AJ, Xu B. Differential diagnosis of mild cognitive impairment of Alzheimer’s disease by Simoa p-tau181 measurements with matching plasma and CSF. Frontiers in Molecular Neuroscience. 2024; 16. DOI: 10.3389/fnmol.2023.1288930
McGettigan S, Nolan Y, Ghosh S, O’Mahony D. The emerging role of blood biomarkers in diagnosis and treatment of Alzheimer’s disease. European Geriatric Medicine. 2023; 14(5): 913-7. DOI: 10.1007/s41999-023-00847-1
Downloads
Published
Issue
Section
License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
Creative Commons License CC-BY-ND
