PMID- 30572951 OWN - NLM STAT- MEDLINE DCOM- 20190529 LR - 20240229 IS - 2046-4053 (Electronic) IS - 2046-4053 (Linking) VI - 7 IP - 1 DP - 2018 Dec 20 TI - CSF and blood biomarkers in amyotrophic lateral sclerosis: protocol for a systematic review and meta-analysis. PG - 237 LID - 10.1186/s13643-018-0913-4 [doi] LID - 237 AB - BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a highly progressive and debilitating neurodegenerative disease, which usually leads to the death of affected individuals within a few years after the onset of symptoms. ALS is currently incurable and very little is known about its pathophysiology. Finding validated biomarkers will help us to advance our understanding of ALS etiology and find better strategies for early diagnosis and management of the disease. The main aim of the present systematic review is to evaluate the concentration of 11 frequently reported biomarkers for ALS in peripheral blood and CSF of patients diagnosed with ALS compared with controls. METHODS: This systematic review protocol has been established according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocol (PRISMA-P) 2015 guideline. We will include all types of observational studies with human subjects that investigated the concentrations of intended biomarkers (amyloid beta (Abeta-42), tau and phosphorylated tau (p-Tau), neurofilaments, S100beta, cystatin C, progranulin (PGRN), glial fibrillary acidic protein (GFAP), monocyte chemoattractant protein-1 (MCP-1), brain-derived neurotrophic factor (BDNF), TAR DNA-binding protein-43 (TDP43), YKL-40, and CHIT1 in CSF or peripheral blood of ALS patients for initial assessment. Also, we will include case series with a minimum of 10 cases and clinical trials which have measured baseline biomarker levels. Case studies, case reports, reviews, letters, and animal and in vitro studies will be excluded. Multiple electronic databases including Cochrane Library, MEDLINE (PubMed), ISI Web of Science, and EMBASE will be searched to find all eligible articles published since 1980. No language restriction will be applied. All titles and abstracts retrieved by searching information sources will be evaluated independently by two authors against the eligibility criteria. The following information will be extracted from each included study by two independent authors: bibliographic details (first author, study title, year of publication, country), demographics and clinical information (number of patients and controls, type of ALS and controls, study design, age, gender, specimen, biomarkers levels, ALS functional rating scale Revised (ALSFRS-R), duration of disease), and measurements (method, value type, biomarkers levels). We will use the extracted mean and standard deviation (SD) of biomarkers concentrations to calculate the standardized mean difference (SMD) and 95% confidence intervals (CI). The primary outcome measures are the mean difference of biomarker levels between ALS patients and controls, different types of ALS, and ALS patients with genetic mutations. DISCUSSION: We will systematically review the literature and analyze studies of biomarker level in CSF and peripheral blood of patients with ALS and controls. The results will help us to identify biomarkers with possible diagnostic and prognostic value. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42017078127. FAU - Agah, Elmira AU - Agah E AD - NeuroImmunology Research Association (NIRA), Universal Scientific Education and Research Network (USERN), Tehran, Iran. AD - Students' Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran. FAU - Saleh, Fatemeh AU - Saleh F AD - NeuroImmunology Research Association (NIRA), Universal Scientific Education and Research Network (USERN), Tehran, Iran. AD - School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. FAU - Sanjari Moghaddam, Hossein AU - Sanjari Moghaddam H AD - NeuroImmunology Research Association (NIRA), Universal Scientific Education and Research Network (USERN), Tehran, Iran. AD - Students' Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran. AD - Research Center for Immunodeficiencies (RCID), Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran. FAU - Saghazadeh, Amene AU - Saghazadeh A AD - Research Center for Immunodeficiencies (RCID), Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran. AD - Systematic Review and Meta-analysis Expert Group (SRMEG), Universal Scientific Education and Research Network (USERN), Boston, MA, USA. FAU - Tafakhori, Abbas AU - Tafakhori A AD - NeuroImmunology Research Association (NIRA), Universal Scientific Education and Research Network (USERN), Tehran, Iran. a_tafakhori@sina.tums.ac.ir. AD - Iranian Center of Neurological Research (ICNR), Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran. a_tafakhori@sina.tums.ac.ir. FAU - Rezaei, Nima AU - Rezaei N AD - Research Center for Immunodeficiencies (RCID), Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran. rezaei_nima@tums.ac.ir. AD - Systematic Review and Meta-analysis Expert Group (SRMEG), Universal Scientific Education and Research Network (USERN), Boston, MA, USA. rezaei_nima@tums.ac.ir. AD - Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. rezaei_nima@tums.ac.ir. LA - eng PT - Journal Article DEP - 20181220 PL - England TA - Syst Rev JT - Systematic reviews JID - 101580575 RN - 0 (Amyloid beta-Peptides) RN - 0 (Biomarkers) SB - IM MH - Humans MH - Amyloid beta-Peptides MH - *Amyotrophic Lateral Sclerosis/physiopathology MH - *Biomarkers/blood/cerebrospinal fluid MH - *Observational Studies as Topic MH - Prognosis MH - Meta-Analysis as Topic MH - Systematic Reviews as Topic PMC - PMC6300914 OTO - NOTNLM OT - ALS OT - Amyotrophic lateral sclerosis OT - Biological marker OT - Biomarker OT - Neurodegeneration COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: No primary data will be collected, and all required information will be extracted from previously published articles. Therefore, there is no need for ethics. CONSENT FOR PUBLICATION: Not applicable. COMPETING INTERESTS: The authors declare that they have no competing interests. PUBLISHER'S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. EDAT- 2018/12/24 06:00 MHDA- 2019/05/29 06:00 PMCR- 2018/12/20 CRDT- 2018/12/22 06:00 PHST- 2017/06/26 00:00 [received] PHST- 2018/12/09 00:00 [accepted] PHST- 2018/12/22 06:00 [entrez] PHST- 2018/12/24 06:00 [pubmed] PHST- 2019/05/29 06:00 [medline] PHST- 2018/12/20 00:00 [pmc-release] AID - 10.1186/s13643-018-0913-4 [pii] AID - 913 [pii] AID - 10.1186/s13643-018-0913-4 [doi] PST - epublish SO - Syst Rev. 2018 Dec 20;7(1):237. doi: 10.1186/s13643-018-0913-4.