Comparison of plasma and CSF biomarkers across ethnoracial groups in ADNI

Abstract

Background Differences in CSF and plasma Alzheimer’s disease biomarkers between African Americans (AA), Latinos (LA), and non‐Hispanic Whites (NHW) have been reported. The Alzheimer’s Disease Neuroimaging Initiative (ADNI) may offer insights into ethnoracial biomarker differences important for understanding disease trajectory variations among diverse populations. Method We queried the ADNI database for all participants with available plasma pTau181 and NfL (Simoa) and linked CSF biomarkers within 1 year of blood draw (Aβ42, pTau181, T‐tau, Elecsys). Baseline data for 47 AA and 43 LA with plasma biomarkers were matched to separate groups of NHW (1:3 nearest neighbor matching on propensity score), considering age, sex, education, CDR, APOE ε4 alleles and family history of dementia (Table 1). Cross‐sectional analyses compared biomarker levels between matched cohorts without (non‐parametric Mann‐Whitney U‐test) and with adjustment for demographics, clinical, biomarker, and medical characteristics (multi‐linear regression). Statistical threshold was set at two‐tailed p<0.05. Result Unadjusted comparisons between AA and NHW revealed no significant differences in plasma NfL [29.3 (IQR: 21.6‐42.5) vs 35.5 (27.0‐49.6), p=.12], plasma pTau181 [14.5 (9.4‐22.9) vs 15.5 (10.1‐22.8), p=.83], CSF Aβ42 [933.1 (649.5‐1590.8) vs 926.7 (677.7‐1697.8), p=.83], CSF T‐tau [214.6 (152.4‐290.7) vs 251.9 (194.5‐351.4), p=.17] or CSF pTau181 [19.6 (14.4‐27.3) vs 22.7 (17.0‐33.3), p=.32] (Fig. 1a‐b). No significant differences were identified in any of the biomarkers after adjustment for relevant covariates. Unadjusted comparisons between LA and NHW revealed no significant differences in plasma NfL [36.7 (24.4‐50.4) vs 35.6 (25.6‐47.1), p=1], plasma pTau181 [18.0 (11.3‐25.0) vs 15.7 (10.9‐23.4), p=.81], or CSF Aβ42 [852.7 (787.1‐1213.0) vs 951.6 (651.1‐1530.5), p=1]. A trend towards lower CSF T‐Tau [216.5 (147.1‐270.5) vs 257.2 (197.2‐360.9), p=.076] and CSF pTau181 [19.4 (13.6‐27.9) vs 24.7 (17.5‐33.4), p=.076] in LA was observed (Fig. 2a‐b). After adjustment for covariates, LA were found to have significantly lower levels of CSF T‐tau (β=0.154, p<.05) and CSF pTau181 (β=0.164, p<.05), while differences in plasma markers were not significant. Conclusion No significant biomarker differences between AA and NHW were observed. Lower CSF pTau181 and CSF T‐Tau in LA compared to NHW after covariate adjustment may represent subtle differences driven by biological factors or unmeasured sociocultural determinants (income, occupation, neighborhood environment); larger studies are needed.

The Alzheimer's Association appropriate use recommendations for blood biomarkers in Alzheimer's disease

“…Further, a very relevant factor that might affect plasma biomarker levels is ethnicity, which is only beginning to be explored 5 . Studies report contradictory results regarding lower plasma levels of p‐tau in, for example Black or Latin American populations 75–77 . Observed differences may have been dependent on differences in comorbidities, socioeconomic, and educational factors, 76 and whether these factors have different effects at every disease stage is currently unknown.…”

“…Studies report contradictory results regarding lower plasma levels of p‐tau in, for example Black or Latin American populations 75–77 . Observed differences may have been dependent on differences in comorbidities, socioeconomic, and educational factors, 76 and whether these factors have different effects at every disease stage is currently unknown. Thus, it is relevant to further study and consider potential confounding factors, such as socioeconomic factors next to other medical factors, for example, kidney function and BMI.…”

Plasma biomarkers for neurodegenerative disorders: ready for prime time?

“…A few reports have suggested that plasma biomarker levels and performances tend to differ between participants of different ethnoracial backgrounds [62 ▪▪ ,63 ▪▪ ] whereas another study did not report any differences [64 ▪▪ ]. Importantly, other studies have pointed to a likelihood that the intensity of brain pathological changes appear to be less pronounced in participants of non-European ancestry who also tend to be less affected by the presence of the major genetic risk APOE ε4 [65 ▪▪ ,66].…”

The iterative process of fluid biomarker development and validation in Alzheimer's disease

“…tested whether there are differences in plasma and CSF biomarkers among participants in the multi-site Alzheimer's Disease Neuroimaging Initiative (ADNI) study when stratified by race and ethnicity, and controlling for factors that included measured sociodemographic variables and history of cardiovascular disease. 7 Considering the role of confounding health conditions, Berry et al…”

“…With regard to examining blood biomarkers among diverse research participants, Windon et al. leveraged fluid biomarker data collected in the ADNI study 7 . They examined CSF Aβ42, total tau, and p‐tau181 concentrations and plasma p‐tau181 and NfL concentrations in 47 Black participants matched to 141 Non‐Hispanic White participants and 43 Latino participants matched to 129 Non‐Hispanic White participants.…”