INS NYC 2024 Program

Poster	Poster Session 05 Program Schedule 02/15/2024 02:30 pm - 03:45 pm Room: Shubert Complex (Posters 1-60) Poster Session 05: Neuropsychiatry \| Addiction/Dependence \| Stress/Coping \| Emotional/Social Processes Final Abstract #45 Plasma–Based Protein Biomarkers of Chronic Traumatic Brain Injury: Genetic, Demographic and Injury Correlates Amelia Hicks, Brain Injury Research Center, Icahn School of Medicine at Mount Sinai, New York, United States Enna Selmanovic, Brain Injury Research Center, Icahn School of Medicine at Mount Sinai, New York, United States Kristen Dams-O'Connor, Brain Injury Research Center, Icahn School of Medicine at Mount Sinai, New York, United States Category: Acquired Brain Injury (TBI/Cerebrovascular Injury and Disease - Adult) Keyword 1: traumatic brain injury Objective: Plasma-based protein biomarkers of traumatic brain injury (TBI) can provide important insights into the poly-pathological signatures of chronic TBI. This has not been explored in research to-date. Biomarker discovery efforts have focused on the acute post-injury period and examined single proteins. To accurately model the unique impact of TBI on biomarker levels, it is necessary to understand how potentially confounding factors, such as demographic characteristics and genetics, may impact these associations. Furthermore, knowledge gaps remain with respect to how injury factors (severity, frequency) influence biomarker levels. Here we explore the associations between multiple protein biomarkers reflecting neuronal and glial injury in the chronic post-injury period. We also explore the influence of genetic, demographic and injury factors on protein expression. Participants and Methods: This prospective longitudinal study recruited participants with a history of complicated mild-severe TBI exposure at least 1 year prior. TBI exposure was defined by medical records and the Brain Injury Screening Questionnaire. Blood samples were acquired for analysis of protein expression (neuronal injury - AB40, AB42, p-tau231, brain-derived tau, NfL; glial injury - GFAP) using the Simoa platform (Quanterix, Lexington, MA, USA). Genomic data were genotyped for the APOE e2/e3/e4 polymorphisms. Kendall’s correlations and Mann-Whitney U-Tests explored the associations between proteins, and between protein levels with demographic factors (age, sex – male vs female, ethnicity - Hispanic or Latino vs not Hispanic or Latino), APOE genotype (e4 carrier vs non-carrier) and injury severity (mild vs mild-complicated to severe). Results: Plasma samples were analyzed from 128 individuals with chronic TBI (M = 11.9 years; SD = 9.6 years since injury). Bivariate correlations between the six proteins (n=15 correlations), identified 14 statistically significant correlations (Kendall’s tau 0.14 - 0.55; < .05). There were moderate associations (Kendall’s tau 0.42 - 0.55; < .05) between AB40 and AB42, GFAP and NfL, and ptau231 and bd-tau. All other associations were considered small (Kendall’s tau 0.14 - 0.29; < .05). The only non-significant correlation was between AB42 and ptau231. When grouped by APOE genotype, there were significant differences in the level of AB42 only, with the level of AB42 expression lower in carriers (M 5.9; Md 5.6; SD 1.9) than non-carriers (M 6.5; Md 6.38; SD 1.35). Among demographic variables, only age was significantly correlated (Kendall’s tau; < .05) with all proteins except for AB42. There were no group differences in any protein levels by sex or ethnicity. When participants were grouped by TBI severity, there was higher levels of GFAP in the more severe group (M 94.25; Md 84.7; SD 49.65) compared to the mild group (M 66.36; Md 52.7; SD 37.77); and higher levels of NfL in the more severe group (M 15.44; Md 10.65; SD 13.55) compared to the mild group (M 9.35; Md 7.43; SD 6.00). Conclusions: In the chronic post-injury period, the expression of multiple markers of neuronal and glial injury are highly intercorrelated, underscoring the importance of measuring multiple proteins to characterize long-term poly-pathology. Our findings also emphasize that age should be included when modelling the impact of TBI on biomarker levels, and APOE carrier status should also be considered for analyses of AB42. Finally, injury severity is an important determinant of chronic elevations in neuronal (NfL) and glial injury (GFAP) makers.

Poster

02/15/2024
02:30 pm - 03:45 pm
Room: Shubert Complex (Posters 1-60)

Poster Session 05: Neuropsychiatry | Addiction/Dependence | Stress/Coping | Emotional/Social Processes

Final Abstract #45

Plasma–Based Protein Biomarkers of Chronic Traumatic Brain Injury: Genetic, Demographic and Injury Correlates

Amelia Hicks, Brain Injury Research Center, Icahn School of Medicine at Mount Sinai, New York, United States
Enna Selmanovic, Brain Injury Research Center, Icahn School of Medicine at Mount Sinai, New York, United States
Kristen Dams-O'Connor, Brain Injury Research Center, Icahn School of Medicine at Mount Sinai, New York, United States

Category: Acquired Brain Injury (TBI/Cerebrovascular Injury and Disease - Adult)

Keyword 1: traumatic brain injury

Objective:

Plasma-based protein biomarkers of traumatic brain injury (TBI) can provide important insights into the poly-pathological signatures of chronic TBI. This has not been explored in research to-date. Biomarker discovery efforts have focused on the acute post-injury period and examined single proteins. To accurately model the unique impact of TBI on biomarker levels, it is necessary to understand how potentially confounding factors, such as demographic characteristics and genetics, may impact these associations. Furthermore, knowledge gaps remain with respect to how injury factors (severity, frequency) influence biomarker levels. Here we explore the associations between multiple protein biomarkers reflecting neuronal and glial injury in the chronic post-injury period. We also explore the influence of genetic, demographic and injury factors on protein expression.

Participants and Methods:

This prospective longitudinal study recruited participants with a history of complicated mild-severe TBI exposure at least 1 year prior. TBI exposure was defined by medical records and the Brain Injury Screening Questionnaire. Blood samples were acquired for analysis of protein expression (neuronal injury - AB40, AB42, p-tau231, brain-derived tau, NfL; glial injury - GFAP) using the Simoa platform (Quanterix, Lexington, MA, USA). Genomic data were genotyped for the APOE e2/e3/e4 polymorphisms. Kendall’s correlations and Mann-Whitney U-Tests explored the associations between proteins, and between protein levels with demographic factors (age, sex – male vs female, ethnicity - Hispanic or Latino vs not Hispanic or Latino), APOE genotype (e4 carrier vs non-carrier) and injury severity (mild vs mild-complicated to severe).

Results:

Plasma samples were analyzed from 128 individuals with chronic TBI (M = 11.9 years; SD = 9.6 years since injury). Bivariate correlations between the six proteins (n=15 correlations), identified 14 statistically significant correlations (Kendall’s tau 0.14 - 0.55; < .05). There were moderate associations (Kendall’s tau 0.42 - 0.55; < .05) between AB40 and AB42, GFAP and NfL, and ptau231 and bd-tau. All other associations were considered small (Kendall’s tau 0.14 - 0.29; < .05). The only non-significant correlation was between AB42 and ptau231. When grouped by APOE genotype, there were significant differences in the level of AB42 only, with the level of AB42 expression lower in carriers (M 5.9; Md 5.6; SD 1.9) than non-carriers (M 6.5; Md 6.38; SD 1.35). Among demographic variables, only age was significantly correlated (Kendall’s tau; < .05) with all proteins except for AB42. There were no group differences in any protein levels by sex or ethnicity. When participants were grouped by TBI severity, there was higher levels of GFAP in the more severe group (M 94.25; Md 84.7; SD 49.65) compared to the mild group (M 66.36; Md 52.7; SD 37.77); and higher levels of NfL in the more severe group (M 15.44; Md 10.65; SD 13.55) compared to the mild group (M 9.35; Md 7.43; SD 6.00).

Conclusions:

In the chronic post-injury period, the expression of multiple markers of neuronal and glial injury are highly intercorrelated, underscoring the importance of measuring multiple proteins to characterize long-term poly-pathology. Our findings also emphasize that age should be included when modelling the impact of TBI on biomarker levels, and APOE carrier status should also be considered for analyses of AB42. Finally, injury severity is an important determinant of chronic elevations in neuronal (NfL) and glial injury (GFAP) makers.