Plasma p-tau217 concordance with amyloid PET among ethnically diverse older adults

Abstract

Introduction: Commercially available plasma p-tau217 biomarker tests are not well studied in ethnically diverse samples.

Methods: We evaluated associations between ALZPath plasma p-tau217 and amyloid-beta positron emission tomography (Aβ-PET) in Hispanic/Latino (88% of Cuban or South American ancestry) and non-Hispanic/Latino older adults. One- and two-cutoff ranges were derived and evaluated to assess agreement with Aβ-PET.

Results: A total of 239 participants underwent blood draw and Aβ-PET (age 70.8 ± 7.8, 55.2% female, education 15.6 ± 3.4 years, 48.9% Hispanic/Latino, 94.9% white). Plasma p-tau217 showed excellent discrimination of Aβ-PET positive and negative participants (visual read: AUC = 0.91 [0.87-0.95], p < 0.001; Centiloids quantification: AUC = 0.90 [0.86-0.94]). There was a greater percent agreement between low p-tau217 and negative Aβ-PET (95.8%) than high p-tau217 and positive Aβ-PET (86.3%). Analyses within ethnicity-specific subgroups suggested similar p-tau217 performance.

Discussion: Plasma p-tau217 (ALZPath) relates to brain Aβ in Hispanic/Latino and non-Hispanic/Latino older adults. Independent validation and replication are necessary to establish reference ranges and inform appropriate contexts of use across ethno-racially diverse populations.

Highlights: Plasma p-tau217 (ALZPath) and Aβ-PET were measured in Hispanic/Latino and non-Hispanic/Latino older adults.Plasma p-tau217 accurately discriminated Aβ-PET positive and negative participants.Applying a two-cutoff "intermediate" plasma p-tau217 approach could reduce need for more invasive and costly testing.Plasma p-tau217 associations with Aβ-PET were strong within both Hispanic/Latino and non-Hispanic/Latino groups.

Keywords: ALZPath; Alzheimer's; Hispanic; Latino; amyloid PET; biomarkers; dementia; ethnicity; plasma; p‐tau217.

FIGURE 1

Receiver operating characteristic (ROC) curves showing plasma p‐tau217 discriminability of positive versus negative amyloid‐beta positron emission tomography (Aβ‐PET) results based on different interpretation methods and thresholds. (A–C) Visual read interpretation of Aβ‐PET results for the overall sample (panel A, All Participants) and separately within non‐Hispanic/Latino white (B) and Hispanic/Latino white (C) groups. (D–F) Centiloids‐based quantification of positive versus negative Aβ‐PET based on a threshold of 25 Centiloids for the overall sample (D), within non‐Hispanic/Latino white (E), and within Hispanic/Latino white (F). Area under the curve (AUC) estimate with 95% confidence interval is shown for each. See Tables 2, 3, 4 for corresponding single‐ and two‐cutoff ranges of p‐tau217 concentrations.

FIGURE 2

Receiver operating characteristic (ROC) curves showing plasma p‐tau217 discriminability of different levels of amyloid‐beta (Aβ) burden on Aβ‐positron emission tomography (PET) (“Low,” “Intermediate,” “High”). (A‐C) Plasma p‐tau217 discriminability of Low (Centiloids < 10) vs. High (Centiloids > 49) Aβ‐PET burden for the overall sample (A, All Participants) and separately within non‐Hispanic/Latino white (B) and Hispanic/Latino white (C) groups. (D–F) Plasma p‐tau217 discriminability of Low (Centiloids < 10) vs. Intermediate (Centiloids 10–49) Aβ‐PET burden for the overall sample (D), within non‐Hispanic/Latino white (E), and within Hispanic/Latino white (F). Area under the curve (AUC) estimate with 95% confidence interval is shown for each.

FIGURE 3

Scatterplots demonstrating a positive correlation between plasma p‐tau217 and amyloid‐beta (Aβ) burden measured in Centiloids for the overall sample (A) and separately within non‐Hispanic/Latino white (B), and Hispanic/Latino white (C) groups. Nonparametric linear association (Spearman's rho) is reported for each with a 95% confidence interval. The vertical dashed line represents the binary Centiloids‐based quantification threshold for a positive Aβ‐positron emission tomography (PET) scan (≥25). The horizontal gray dashed line represents the Youden's index single‐cutoff of plasma p‐tau217 that optimally balances sensitivity and specificity to discriminating a positive and negative Aβ‐PET scan (visual read). An intermediate plasma p‐tau217 range is shown as the lower and upper horizontal red dashed lines, which represent the p‐tau217 with 95% sensitivity (lower) and 95% specificity (upper) for discriminating a positive from negative Aβ‐PET scan (visual read). Participants falling between the red dashed lines represent a potential group that might be recommended to undergo confirmatory biomarker testing (CSF or PET) in a clinical setting. Youden's index and two‐point cutoffs (horizontal dashed lines) shown in panels (B) and (C) are derived from within‐group analyses (i.e., specific to race/ethnicity rather than universal cutoff applied from the overall sample). To limit axis distortion, three participants with Centiloids values were censored (outside axis range).