Head‐to‐head comparison of leading blood tests for Alzheimer's disease pathology

Alzheimer s & Dementia, Journal Year: 2024, Volume and Issue: 20(11), P. 8074 - 8096

Published: Oct. 12, 2024

Abstract INTRODUCTION Blood tests have the potential to improve accuracy of Alzheimer's disease (AD) clinical diagnosis, which will enable greater access AD‐specific treatments. This study compared leading commercial blood for amyloid pathology and other AD‐related outcomes. METHODS Plasma samples from Disease Neuroimaging Initiative were assayed with AD C2N Diagnostics, Fujirebio ALZPath, Janssen, Roche Quanterix. Outcomes measures positron emission tomography (PET), tau PET, cortical thickness, dementia severity. Logistic regression models assessed classification accuracies individual or combined plasma biomarkers binarized outcomes, Spearman correlations evaluated continuous relationships between RESULTS Measures p‐tau217, either individually in combination biomarkers, had strongest all DISCUSSION identified biomarker analytes assays that most accurately classified Highlights p‐tau217 status. Aβ42/Aβ40 relatively low higher thickness than NfL. Correlations symptoms low.

Language: Английский

---

Optimizing cutpoints for clinical interpretation of brain amyloid status using plasma p‐tau217 immunoassays

Alzheimer s & Dementia, Journal Year: 2024, Volume and Issue: 20(9), P. 6506 - 6516

Published: July 19, 2024

Abstract INTRODUCTION We aimed to evaluate clinical interpretation cutpoints for two plasma phosphorylated tau (p‐tau)217 assays (ALZpath and Lumipulse) as predictors of amyloid status implementation in practice. METHODS Clinical performance p‐tau217 against positron emission tomography was evaluated participants with mild cognitive impairment or dementia ( n = 427). RESULTS Using a one‐cutpoint approach (negative/positive), neither assay achieved ≥ 90% both sensitivity specificity. A two‐cutpoint yielding 92% 96% specificity provided the desired balance false positives negatives, while categorizing 20% 39% results indeterminate Lumipulse ALZpath assays, respectively. DISCUSSION This study provides systematic framework selection assay‐specific use determination status. Our findings suggest that may have advantages optimizing diagnostic accuracy minimizing potential harm from positive results. Highlights Phosphorylated detection pathology were established. exhibited best laboratory use. differed percentage categorized intermediate.

Language: Английский

---

Cutting through the noise: A narrative review of Alzheimer's disease plasma biomarkers for routine clinical use

The Journal of Prevention of Alzheimer s Disease, Journal Year: 2025, Volume and Issue: unknown, P. 100056 - 100056

Published: Jan. 1, 2025

As novel, anti-amyloid therapies have become more widely available, access to timely and accurate diagnosis has integral ensuring optimal treatment of patients with early-stage Alzheimer's disease (AD). Plasma biomarkers are a promising tool for identifying AD pathology; however, several technical clinical factors need be considered prior their implementation in routine use. Given the rapid pace advancements field wide array available tests, this review aims summarize these considerations, evaluate platforms, discuss steps needed bring plasma biomarker testing clinic. We focus on phosphorylated(p)-tau, specifically p-tau217, as robust candidate across both primary secondary care settings. Despite high performance robustness demonstrated research, like all biomarkers, can affected by analytical pre-analytical variability well patient comorbidities, sex, ethnicity, race. This also discusses advantages two-point cut-off approach mitigating factors, challenges raised resulting intermediate range measurements, where guidance is still unclear. Further validation p-tau217 heterogeneous, real-world cohorts will help increase confidence support establishing standardized approach. poised affordable less invasive alternative PET CSF testing. However, understanding that impact measurement interpretation critical

Language: Английский

---

Alzheimer’s disease biomarkers and their current use in clinical research and practice

Molecular Psychiatry, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 4, 2024

Language: Английский

---

Diagnosis of Alzheimer’s disease using plasma biomarkers adjusted to clinical probability

Nature Aging, Journal Year: 2024, Volume and Issue: 4(11), P. 1529 - 1537

Published: Nov. 12, 2024

Abstract Recently approved anti-amyloid immunotherapies for Alzheimer’s disease (AD) require evidence of amyloid-β pathology from positron emission tomography (PET) or cerebrospinal fluid (CSF) before initiating treatment. Blood-based biomarkers promise to reduce the need PET CSF testing; however, their interpretation at individual level and circumstances requiring confirmatory testing are poorly understood. Individual-level diagnostic test results requires knowledge prevalence in relation clinical presentation (clinical pretest probability). Here, a study 6,896 individuals evaluated 11 cohort studies six countries, we determined positive negative predictive value five plasma cognitively impaired probability. We observed that p-tau217 could rule with probable AD dementia (positive above 95%). In mild cognitive impairment, depended on patient age. Negative out non-AD syndromes (negative between 90% 99%). Our findings provide framework individual-level biomarkers, suggesting combined phenotyping can identify patients where be ruled without testing.

Language: Английский

---

Longitudinal plasma phosphorylated‐tau217 and other related biomarkers in a non‐demented Alzheimer's risk‐enhanced sample

Alzheimer s & Dementia, Journal Year: 2024, Volume and Issue: 20(9), P. 6183 - 6204

Published: July 5, 2024

Abstract INTRODUCTION Understanding longitudinal change in key plasma biomarkers will aid detecting presymptomatic Alzheimer's disease (AD). METHODS Serial samples from 424 Wisconsin Registry for Prevention participants were analyzed phosphorylated‐tau217 (p‐tau217; ALZpath) and other AD biomarkers, to study trajectories relation disease, health factors, cognitive decline. Of the participants, 18.6% with known amyloid status positive (A+); 97.2% cognitively unimpaired (CU). RESULTS In CU, amyloid‐negative (A–) subset, p‐tau217 levels increased modestly age but unaffected by body mass index kidney function. whole sample, average rates higher those who A+ (e.g., simple slopes(se) A– at 60 0.232(0.028) 0.038(0.013))). High baseline predicted faster preclinical DISCUSSION stands out among markers its strong association decline, indicating potential early detection monitoring progression. Highlights Phosphorylated‐tau217 (p‐tau217) significantly different people be positive. Subtle age‐related seen all unimpaired. Kidney function not associated trajectories. Higher was

Language: Английский

---

Plasma p-tau217 in Alzheimer’s disease: Lumipulse and ALZpath SIMOA head-to-head comparison

Brain, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 16, 2024

Plasma phosphorylated-tau217 (p-tau217) has been shown to be one of the most accurate diagnostic markers for Alzheimer's disease. No studies have compared clinical performance p-tau217 as assessed by fully automated Lumipulse and single molecule array (SIMOA) AlZpath p-tau217. The study included 392 participants, 162 with disease, 70 other neurodegenerative diseases CSF biomarkers 160 healthy controls. levels were measured using ALZpath SIMOA assays. ability both techniques discriminate disease from controls was investigated receiver operating characteristic analyses. two demonstrated a strong correlation, showing consistent relationship p-tau181 levels. In head-to-head comparison, showed similar accuracy differentiating [area under curve (AUC) 0.952, 95% confidence interval (CI) 0.927-0.978 versus 0.955, CI 0.928-0.982, respectively] (AUC 0.938, 0.910-0.966 0.937, 0.907-0.967 assays). This high precision diagnosis or semi-automated techniques.

Language: Английский

---

Plasma p-tau217 in Alzheimer’s disease: Lumipulse and ALZpath SIMOA head-to-head comparison

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: May 3, 2024

ABSTRACT Background Plasma phosphorylated-tau217 (p-tau217) has been shown to be one of the most accurate diagnostic markers for Alzheimer’s disease (AD). No studies have compared clinical performance p-tau217 as assessed by fully automated Lumipulse and SIMOA ALZpath p-tau217. Aim To evaluate accuracy plasma assays AD. Methods The study included 392 participants, 162 with AD, 70 other neurodegenerative diseases (NDD) CSF biomarkers 160 healthy controls. levels were measured using assays. ability both techniques discriminate AD from NDD controls was investigated ROC analyses. Results Both showed high internal consistency similar correlation p-tau181 levels. In head-to-head comparison, differentiating (area under curve [AUC] 0.952, 95%CI 0.927–0.978 vs 0.955, 0.928–0.982, respectively) HC (AUC 0.938, 0.910-0.966 0.937, 95% CI0.907-0.967 assays). Conclusions This demonstrated precision diagnosis either or semi-automated techniques.

Language: Английский

---

A comprehensive head-to-head comparison of key plasma phosphorylated tau 217 biomarker tests

Brain, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 26, 2024

Abstract Plasma phosphorylated-tau 217 (p-tau217) is currently the most promising biomarker for reliable detection of Alzheimer’s disease (AD) pathology. Various p-tau217 assays have been developed, but their relative performance unclear. We compared key plasma tests using cross-sectional and longitudinal measures amyloid-β (Aβ)-PET, tau-PET, cognition as outcomes, benchmarked them against cerebrospinal fluid (CSF) tests. Samples from 998 individuals (mean[range] age 68.5[20.0-92.5], 53% female) Swedish BioFINDER-2 cohort, including both cognitively unimpaired impaired individuals, were analyzed. was measured with mass spectrometry (MS) (the ratio between phosphorylated non-phosphorylated [%p-tau217WashU] p-tau217WashU) well immunoassays (p-tau217Lilly, p-tau217Janssen, p-tau217ALZpath). CSF biomarkers included p-tau217Lilly, FDA-approved p-tau181/Aβ42Elecsys, p-tau181Elecsys. All exhibited a high ability to detect abnormal Aβ-PET (AUC range: 0.91-0.96) tau-PET 0.94-0.97). %p-tau217WashU had highest performance, significantly higher AUCs than all (Pdiff<0.007). For detecting status, an accuracy 0.93 (immunoassays: 0.83-0.88), sensitivity 91% 84-87%), specificity 94% 85-89%). Among immunoassays, p-tau217Lilly p-tau217ALZpath p-tau217Janssen status (Pdiff<0.006), outperformed (Pdiff=0.025). stronger associations PET load outcomes immunoassays; baseline (R2: 0.72; immunoassays: 0.47-0.58; Pdiff<0.001), 0.51; 0.38-0.45; 0.53; 0.31-0.38; Pdiff<0.001) 0.50; 0.35-0.43; Pdiff<0.014). more associated (Pdiff<0.020) (all Pdiff<0.010). %p-tau217 also correlated strongly (Mini-Mental State Examination[MMSE]) (R2 %p-tau217WashU: 0.33; 0.27-0.30; Pdiff<0.024). The main results replicated in external cohort Washington University St Louis (n =219). Finally, p-tau217NULISA showed similar other subsets cohorts. In summary, MS- immunoassay-based generally perform identifying Aβ-PET, cognitive abnormalities, performed better examined immunoassays. may be considered stand-alone confirmatory test AD pathology, while some might suited triage where positive are confirmed second test, which needs determined by future reviews incorporating multiple

Language: Английский

---

A Comprehensive Head-to-Head Comparison of Key Plasma Phosphorylated Tau 217 Biomarker Tests

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 5, 2024

Abstract Plasma phosphorylated-tau 217 (p-tau217) is currently the most promising biomarkers for reliable detection of Alzheimer’s disease (AD) pathology. Various p-tau217 assays have been developed, but their relative performance unclear. We compared key plasma tests using cross-sectional and longitudinal measures amyloid-β (Aβ)-PET, tau-PET, cognition as outcomes, benchmarked them against cerebrospinal fluid (CSF) biomarker tests. Samples from 998 individuals (mean[range] age 68.5[20.0-92.5], 53% female) Swedish BioFINDER-2 cohort were analyzed. was measured with mass spectrometry (MS) (the ratio between phosphorylated non-phosphorylated [%p-tau217 WashU ]and ) well immunoassays (p-tau217 Lilly , Janssen ALZpath ). CSF included FDA-approved p-tau181/Aβ42 Elecsys p-tau181 . All exhibited high ability to detect abnormal Aβ-PET (AUC range: 0.91-0.96) tau-PET 0.94-0.97). %p-tau217 had highest performance, significantly higher AUCs than all ( P diff <0.007). For detecting status, an accuracy 0.93 (immunoassays: 0.83-0.88), sensitivity 91% 84-87%), a specificity 94% 85-89%). Among immunoassays, status <0.006), outperformed =0.025). associations PET load outcomes immunoassays; baseline (R 2 : 0.72; immunoassays: 0.47-0.58; <0.001), 0.51; 0.38-0.45; 0.53; 0.31-0.38; <0.001) 0.50; 0.35-0.43; <0.014). more strongly associated <0.020) both (all <0.010). also correlated (Mini-Mental State Examination[MMSE]) 0.33; 0.27-0.30; <0.024). The main results replicated in external Washington University St Louis n =219). Finally, Nulisa showed similar other subsets cohorts. In summary, MS-and immunoassay-based generally perform identifying Aβ-PET, cognitive abnormalities, performed better examined immunoassays. may be considered stand-alone confirmatory test AD pathology, while some might suited triage where positive are confirmed second test.

Language: Английский

---