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[Preprint]. 2024 Apr 12:2024.04.10.24305617.
doi: 10.1101/2024.04.10.24305617.

Generalizability of Tau and Amyloid Plasma Biomarkers in Alzheimer's Disease Cohorts of Diverse Genetic Ancestries

Anthony J Griswold  1   2 , Farid Rajabli  1   2 , Tianjie Gu  1 , Jamie Arvizu  1 , Charles G Golightly  1 , Patrice L Whitehead  1 , Kara L Hamilton-Nelson  1 , Larry D Adams  1 , Jose Javier Sanchez  1 , Pedro R Mena  1 , Takiyah D Starks  3 , Maryenela Illanes-Manrique  4 , Concepcion Silva  5 , William S Bush  6   7 , Michael L Cuccaro  1   2 , Jeffery M Vance  1   2 , Mario R Cornejo-Olivas  4 , Briseida E Feliciano-Astacio  5 , Goldie S Byrd  3 , Gary W Beecham  1   2 , Jonathan L Haines  6   7 , Margaret A Pericak-Vance  1   2
Affiliations

Generalizability of Tau and Amyloid Plasma Biomarkers in Alzheimer's Disease Cohorts of Diverse Genetic Ancestries

Anthony J Griswold et al. medRxiv. .

Update in

Abstract

Introduction: Plasma phosphorylated threonine-181 of Tau and amyloid beta are biomarkers for differential diagnosis and preclinical detection of Alzheimer disease (AD). Given differences in AD risk across diverse populations, generalizability of existing biomarker data is not assured.

Methods: In 2,086 individuals of diverse genetic ancestries (African American, Caribbean Hispanic, and Peruvians) we measured plasma pTau-181 and Aβ42/Aβ40. Differences in biomarkers between cohorts and clinical diagnosis groups and the potential discriminative performance of the two biomarkers were assessed.

Results: pTau-181 and Aβ42/Aβ40 were consistent across cohorts. Higher levels of pTau181 were associated with AD while Aβ42/Aβ40 had minimal differences. Correspondingly, pTau-181 had greater predictive value than Aβ42/Aβ40, however, the area under the curve differed between cohorts.

Discussion: pTau-181 as a plasma biomarker for clinical AD is generalizable across genetic ancestries, but predictive value may differ. Combining genomic and biomarker data from diverse individuals will increase understanding of genetic risk and refine clinical diagnoses.

Keywords: Alzheimer’s disease; amyloid; diverse ancestry; plasma biomarkers; tau.

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Conflict of interest statement

Conflict of Interest The authors declare no conflicts of interest.

Figures

Figure 1.
Figure 1.
Global genomic ancestry analysis. A) Principal component analyses. Estimation of relationship to ancestral reference groups from Human Genome Diversity Project (HGDP): Maroon = African, Green = Amerindian, Yellow = East Asian, Blue = European, or each sample cohort: Light Green = Cuban American, Violet = Peruvian, Red = Puerto Rican, Aqua = African American. B) Ancestral admixture estimations. Each column on the X-axis represents one participant. Colors in each vertical line represent the proportion of ancestral admixture. Red = African, Blue = European, Green = Amerindian, Yellow = East Asian.
Figure 2.
Figure 2.
AD biomarker levels across ancestral groups African Americans, Peruvians, and Caribbean Hispanics. A) pTau-181 in cognitively unimpaired. B) pTau-181 in AD. C) Aβ42/Aβ40 in cognitively unimpaired. D) Aβ42/Aβ40 in AD. **** p<0.0001, ***p<0.001, **p<0.01, *p<0.05, ns = not significant
Figure 3.
Figure 3.
Plasma pTau-181 comparison analysis. Comparisons of the pTau-181 concentration in clinical diagnosis statuses of Alzheimer Disease (AD), mild cognitively impaired (MCI), or cognitively unimpaired (CU) in: A) The overall combined cohort, B) African Americans, C) Peruvians, and D) Caribbean Hispanics. Each point represents one individual’s pTau-181 measurement. Concentrations are shown as median ± interquartile range, **** p<0.0001, ***p<0.001, **p<0.01, *p<0.05, ns = not significant
Figure 4.
Figure 4.
Plasma Aβ42/Aβ40 ratio comparison analysis. Comparisons of the Aβ42/Aβ40 ratio in clinical diagnosis statuses of Alzheimer Disease (AD), mild cognitively impaired (MCI), or cognitively unimpaired (CU) in: A) The overall combined cohort, B) African Americans, C) Peruvians, and D) Caribbean Hispanics. Each point represents one individual’s Aβ42/Aβ40 ratio. Ratios are shown as median ± interquartile range, *p<0.05, ns = not significant
Figure 5.
Figure 5.
pTau-181 and Aβ42/Aβ40 ratio comparisons in African American plasma and serum analysis. Comparisons of pTau-181 concentrations between serum and plasma in A) cognitively unimpaired (CU) and B) Alzheimer Disease (AD). Aβ42/Aβ40 ratio between serum and plasma in C) cognitively unimpaired (CU) and D) Alzheimer Disease (AD). Each point represents one individual’s measurement. Concentrations are shown as median ± interquartile range. **** p<0.0001, **p<0.01, *p<0.05
Figure 6.
Figure 6.
Serum pTau-181 and Aβ42/Aβ40 ratio comparison analysis. Comparisons of the A) pTau 181 concentration and B) Aβ42/Aβ40 ratio in clinical diagnosis statuses of Alzheimer Disease (AD), mild cognitively impaired (MCI), or cognitively unimpaired (CU) in a subset of African American individuals for which plasma was not available. Each point represents one individual’s measurement. Concentrations are shown as median ± interquartile range. ****p < 0.0001, ns – not significant.
Figure 7.
Figure 7.
Receiver operating characteristic (ROC) curves of plasma and serum biomarkers for the classification of Alzheimer disease status in: A) The overall combined cohort, B) Caribbean Hispanics, C) Peruvians, D) African Americans - plasma, E) African Americans - serum. Red lines represent pTau-181 alone, green lines Aβ42/Aβ40 ratio alone, and blue lines the combination of pTau-181 and Aβ42/Aβ40 ratio.
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