Characterizing Plasma Biomarkers of Alzheimer's in a Diverse Community-Based Cohort: A Cross-Sectional Study of the HAB-HD Cohort

Hall, James; Petersen, Melissa; Johnson, Leigh; O’Bryant, Sid

doi:10.3389/fneur.2022.871947

Cited by 18 publications

(13 citation statements)

References 32 publications

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“…In biomarker studies of more diverse individuals, the utility of pTau-181 has been shown in predicting AD status in Caribbean Hispanics[39] as well as African Americans. [38,55] However, the larger sample sizes of diverse cohorts reported here, 3-5 times larger than previous, indicate that this is a robust and reproducible observation; that pTau-181 can be incorporated in more diverse populations as a potential aide in diagnostic prediction. However, it is clear that this biomarker lacks complete discrimination of status as there is significant overlap in individual values between AD, MCI, and CU.…”

Section: Discussionmentioning

confidence: 45%

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

Griswold,

Rajabli,

et al. 2024

Preprint

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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.

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Section: Discussionmentioning

confidence: 45%

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

Griswold,

Rajabli,

et al. 2024

Preprint

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“…Also, participants of this community‐based cohort were predominantly white. Prior studies examining performance of BBBs in racial and ethnic diverse groups have been conflicting 31 , 32 , 33 , 34 and more data are needed to determine if the diagnostic performance observed in this study is applicable to more diverse populations. Finally, we used amyloid‐PET as the outcome measure; therefore, studies examining performance of BBBs using CSF biomarkers to characterize amyloid pathology may not be directly comparable as CSF markers can also have varying performance for detecting an abnormal amyloid‐PET.…”

Section: Discussionmentioning

confidence: 94%

Performance of the Lumipulse plasma Aβ42/40 and pTau181 immunoassays in the detection of amyloid pathology

Figdore,

Wiste,

Bornhorst

et al. 2024

Alz & Dem Diag Ass & Dis Mo

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INTRODUCTIONThis study evaluated the performance of the Lumipulse plasma beta‐amyloid (Aβ) 42/40 and pTau181 compared to other assays to detect an abnormal amyloid‐positron emission tomography (PET).METHODSPlasma samples from cognitively unimpaired (N = 179) and MCI/AD dementia (N = 36) individuals were retrospectively evaluated. Plasma Aβ42/40 and pTau181 were measured using the Lumipulse and Simoa immunoassays. An immunoprecipitation mass spectrometry (IP‐MS) assay for plasma Aβ42/40 was also evaluated. Amyloid‐PET status was the outcome measure.RESULTSLumipulse and IP‐MS Aβ42/40 exhibited the highest diagnostic accuracy for detecting an abnormal amyloid‐PET (areas under the curve [AUCs] of 0.81 and 0.84, respectively). The Lumipulse and Simoa pTau181 assays exhibited lower performance (AUCs of 0.74 and 0.72, respectively). The Simoa Aβ42/40 assay demonstrated the lowest diagnostic accuracy (AUC 0.57). Combining Aβ42/40 and pTau181 did not significantly improve performance over Aβ42/40 alone for Lumipulse (AUC 0.83) or over pTau181 alone for Simoa (AUC 0.71)DISCUSSIONThe Lumipulse Aβ42/40 assay showed similar performance to the IP‐MS Aβ42/40 assay for detection of an abnormal amyloid‐PET; and both assays performed better than the two p‐tau181 immunoassays. The Simoa Aβ42/Aβ40 assay was the least accurate at predicting an abnormal amyloid‐PET status.Highlights Lumipulse plasma Aβ42/Aβ40 AUC for abnormal amyloid‐PET detection was 0.81. This performance was comparable to previously reported IP‐MS and higher than Simoa. Performance of Alzheimer's disease blood biomarkers varies between assays.

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“…Notably, recent findings from another cohort of non‐Hispanic Whites and Black Americans suggest that while plasma Aβ42/40 consistently predicted CSF Aβ42/40 across self‐identified racialized groups, other plasma biomarkers, including phosphorylated tau (p‐tau)181, p‐tau231, and neurofibrillary tangle levels were not as consistently aligned 2 . Moreover, recent evidence suggesting differences in plasma Aβ42/40 levels between racialized groups carrying the same neurocognitive diagnoses (e.g., MCI and dementia) underscores the importance of this ongoing work 3 . In total, expansion of biomarker research in Black American cohorts 44 represents an essential next step to ensure that biomarkers accurately and consistently predict AD pathology across diverse populations.…”

Section: Discussionmentioning

confidence: 99%

Plasma Aβ42/40 and cognitive variability are associated with cognitive function in Black Americans: Findings from the AA‐FAIM cohort

Fischer,

Van Hulle,

Langhough

et al. 2023

A&D Transl Res & Clin Interv

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IntroductionIt is critical to develop more inclusive Alzheimer's disease (AD) research protocols to ensure that historically excluded groups are included in preclinical research and have access to timely diagnosis and treatment. If validated in racialized groups, plasma AD biomarkers and measures of subtle cognitive dysfunction could provide avenues to expand diversity in preclinical AD research. We sought to evaluate the utility of two easily obtained, low‐burden disease markers, plasma amyloid beta (Aβ)42/40, and intra‐individual cognitive variability (IICV), to predict concurrent and longitudinal cognitive performance in a sample of Black adults.MethodsTwo hundred fifty‐seven Black participants enrolled in the African Americans Fighting Alzheimer's in Midlife (AA‐FAIM) study underwent at least one cognitive assessment visit; a subset of n = 235 had plasma samples. Baseline IICV was calculated as the standard deviation across participants’ z scores on five cognitive measures: Rey Auditory Verbal Learning Test Delayed Recall, Trail Making Test Parts A and B (Trails A and B), and Boston Naming Test. Using mixed effects regression models, we compared concurrent and longitudinal models to baseline plasma Aβ42/40 or IICV by age interactions. PrecivityAD assays quantified baseline plasma Aβ42/40.ResultsIICV was associated with concurrent/baseline performance on several outcomes but did not modify associations between age and cognitive decline. In contrast, plasma Aβ42/40 was unrelated to baseline cognitive performance, but a pattern emerged in interactions with age in longitudinal models of Trails A and B and Rey Auditory Verbal Learning Test total learning trials. Although not significant after correcting for multiple comparisons, low Aβ42/40 was associated with faster cognitive declines over time.DiscussionOur results are promising as they extend existing findings to an Black American sample using low‐cost, low‐burden methods that can be implemented outside of a research center, thus supporting efforts for inclusive AD biomarker research.

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Characterizing Plasma Biomarkers of Alzheimer's in a Diverse Community-Based Cohort: A Cross-Sectional Study of the HAB-HD Cohort

Cited by 18 publications

References 32 publications

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

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

Performance of the Lumipulse plasma Aβ42/40 and pTau181 immunoassays in the detection of amyloid pathology

Plasma Aβ42/40 and cognitive variability are associated with cognitive function in Black Americans: Findings from the AA‐FAIM cohort

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