Jean Ikanga, Kharine Jean, Priscilla Medina, Saranya Sundaram Patel, Megan Claire Schwinne, Emmanuel Epenge, Guy Gikelekele, Nathan Tshengele, Immaculee Kavugho, Samuel Mampunza, Lelo Mananga, Charlotte Teunissen, Anthony Stringer, Julio Rojas, Brandon Chan, Argentina Lario Lago, Joel Kramer, Adam Boxer, Andreas Jeromin, Alden Gross, Alvaro Alonso
{"title":"Preliminary reference values for Alzheimers disease plasma biomarkers in Congolese individuals with and without Alzheimers disease","authors":"Jean Ikanga, Kharine Jean, Priscilla Medina, Saranya Sundaram Patel, Megan Claire Schwinne, Emmanuel Epenge, Guy Gikelekele, Nathan Tshengele, Immaculee Kavugho, Samuel Mampunza, Lelo Mananga, Charlotte Teunissen, Anthony Stringer, Julio Rojas, Brandon Chan, Argentina Lario Lago, Joel Kramer, Adam Boxer, Andreas Jeromin, Alden Gross, Alvaro Alonso","doi":"10.1101/2024.08.06.24311577","DOIUrl":null,"url":null,"abstract":"Background: Western countries have provided reference values (RV) for Alzheimers disease (AD) plasma biomarkers, but there are not available in Sub-Saharan African populations. Objective: We provide preliminary RV for AD and other plasma biomarkers including amyloid-β (AB;42/40), phosphorylated tau-181 and 217 (p-tau181, p-tau217), neurofilament light (Nfl), glial fibrillary acidic protein (GFAP), interleukin 1b and 10 (IL-1b and IL-10) and tumor necrosis factor a; (TNFa) in Congolese adults with and without dementia. Methods: 85 adults (40 healthy and 45 dementia) over 50 years old were included. Blood samples were provided for plasma AD biomarkers AB;42/40 and p-tau181, p-tau217; Nfl and GFAP; IL-1b and IL-10 and TNFa; analyzed using SIMOA. Linear and logistic regressions were conducted to evaluate differences in biomarkers by age and gender and neurological status, and for the prediction of dementia status by each individual biomarker. RV were those that optimized sensitivity and specificity based on Youdens index. Results: In this sample of 85 adults, 40 (47%) had dementia, 38 (45.0%) were male, overall mean age was 73.2 (SD 7.6) years with 8.3 (5.4) years of education. There were no significant differences in age, gender, and education based on neurological status. Biomarker concentrations did not significantly differ by age except for p-tau181 and GFAP and did not differ by sex. Preliminary cutoffs of various plasma in pg/ml were 0.061 for AB;42/40, 4.50 for p-tau 181, 0.008 for p-tau 217, 36.5 for Nfl, 176 for GFAP, 1.16 for TNFa, 0.011 for IL-1b, and 0.38 for IL-10. All AUCs ranged between 0.64-0.74. P-tau 217 [0.74 (0.61, 0.86)] followed by GFAP [0.72 (0.61, 0.83), and Nfl [0.71 (0.60, 0.82)] had the highest AUC compared to other plasma biomarkers. Conclusions: This study provides RV which could be of preliminary utility to facilitate the screening, clinical diagnostic adjudication, classification, and prognosis of AD in Congolese adults.","PeriodicalId":501367,"journal":{"name":"medRxiv - Neurology","volume":"86 1","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"medRxiv - Neurology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1101/2024.08.06.24311577","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Western countries have provided reference values (RV) for Alzheimers disease (AD) plasma biomarkers, but there are not available in Sub-Saharan African populations. Objective: We provide preliminary RV for AD and other plasma biomarkers including amyloid-β (AB;42/40), phosphorylated tau-181 and 217 (p-tau181, p-tau217), neurofilament light (Nfl), glial fibrillary acidic protein (GFAP), interleukin 1b and 10 (IL-1b and IL-10) and tumor necrosis factor a; (TNFa) in Congolese adults with and without dementia. Methods: 85 adults (40 healthy and 45 dementia) over 50 years old were included. Blood samples were provided for plasma AD biomarkers AB;42/40 and p-tau181, p-tau217; Nfl and GFAP; IL-1b and IL-10 and TNFa; analyzed using SIMOA. Linear and logistic regressions were conducted to evaluate differences in biomarkers by age and gender and neurological status, and for the prediction of dementia status by each individual biomarker. RV were those that optimized sensitivity and specificity based on Youdens index. Results: In this sample of 85 adults, 40 (47%) had dementia, 38 (45.0%) were male, overall mean age was 73.2 (SD 7.6) years with 8.3 (5.4) years of education. There were no significant differences in age, gender, and education based on neurological status. Biomarker concentrations did not significantly differ by age except for p-tau181 and GFAP and did not differ by sex. Preliminary cutoffs of various plasma in pg/ml were 0.061 for AB;42/40, 4.50 for p-tau 181, 0.008 for p-tau 217, 36.5 for Nfl, 176 for GFAP, 1.16 for TNFa, 0.011 for IL-1b, and 0.38 for IL-10. All AUCs ranged between 0.64-0.74. P-tau 217 [0.74 (0.61, 0.86)] followed by GFAP [0.72 (0.61, 0.83), and Nfl [0.71 (0.60, 0.82)] had the highest AUC compared to other plasma biomarkers. Conclusions: This study provides RV which could be of preliminary utility to facilitate the screening, clinical diagnostic adjudication, classification, and prognosis of AD in Congolese adults.