Blood biomarkers for Alzheimer’s disease in clinical practice and trials

Nature Aging, Год журнала: 2023, Номер 3(5), С. 506 - 519

Опубликована: Май 18, 2023

Язык: Английский

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Highly accurate blood test for Alzheimer’s disease is similar or superior to clinical cerebrospinal fluid tests

Nature Medicine, Год журнала: 2024, Номер 30(4), С. 1085 - 1095

Опубликована: Фев. 21, 2024

With the emergence of Alzheimer's disease (AD) disease-modifying therapies, identifying patients who could benefit from these treatments becomes critical. In this study, we evaluated whether a precise blood test perform as well established cerebrospinal fluid (CSF) tests in detecting amyloid-β (Aβ) plaques and tau tangles. Plasma %p-tau217 (ratio phosporylated-tau217 to non-phosphorylated tau) was analyzed by mass spectrometry Swedish BioFINDER-2 cohort (n = 1,422) US Charles F. Joanne Knight Alzheimer Disease Research Center (Knight ADRC) 337). Matched CSF samples were with clinically used FDA-approved automated immunoassays for Aβ42/40 p-tau181/Aβ42. The primary secondary outcomes detection brain Aβ or pathology, respectively, using positron emission tomography (PET) imaging reference standard. Main analyses focused on individuals cognitive impairment (mild mild dementia), which is target population available treatments. equivalent classifying PET status, an area under curve (AUC) both between 0.95 0.97. generally superior classification tau-PET AUCs 0.95-0.98. cognitively impaired subcohorts (BioFINDER-2: n 720; ADRC: 50), plasma had accuracy, positive predictive value negative 89-90% 87-88% tests, further improving 95% two-cutoffs approach. Blood demonstrated performance that AD pathology. Use high-performance clinical practice can improve access accurate diagnosis AD-specific

Язык: Английский

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Blood-based biomarkers for Alzheimer’s disease: Current state and future use in a transformed global healthcare landscape

Neuron, Год журнала: 2023, Номер 111(18), С. 2781 - 2799

Опубликована: Июнь 8, 2023

Язык: Английский

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Plasma proteomic profiles predict future dementia in healthy adults

Nature Aging, Год журнала: 2024, Номер 4(2), С. 247 - 260

Опубликована: Фев. 12, 2024

Язык: Английский

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Detection and treatment of Alzheimer’s disease in its preclinical stage

Nature Aging, Год журнала: 2023, Номер 3(5), С. 520 - 531

Опубликована: Май 18, 2023

Язык: Английский

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Biomarker-based staging of Alzheimer disease: rationale and clinical applications

Nature Reviews Neurology, Год журнала: 2024, Номер 20(4), С. 232 - 244

Опубликована: Март 1, 2024

Язык: Английский

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Disease staging of Alzheimer’s disease using a CSF-based biomarker model

Nature Aging, Год журнала: 2024, Номер 4(5), С. 694 - 708

Опубликована: Март 21, 2024

Abstract Biological staging of individuals with Alzheimer’s disease (AD) may improve diagnostic and prognostic workup dementia in clinical practice the design trials. In this study, we used Subtype Stage Inference (SuStaIn) algorithm to establish a robust biological model for AD using cerebrospinal fluid (CSF) biomarkers. Our analysis involved 426 participants from BioFINDER-2 was validated 222 Knight Alzheimer Disease Research Center cohort. SuStaIn identified singular biomarker sequence revealed that five CSF biomarkers effectively constituted reliable (ordered: Aβ42/40, pT217/T217, pT205/T205, MTBR-tau243 non-phosphorylated mid-region tau). The stages (0–5) demonstrated correlation increased abnormalities other AD-related biomarkers, such as Aβ-PET tau-PET, aligned longitudinal changes reflective progression. Higher at baseline were associated an elevated hazard ratio decline. This study highlights common molecular pathway underlying pathophysiology across all patients, suggesting single collection can accurately indicate presence pathologies characterize stage proposed has implications enhancing assessments both

Язык: Английский

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Diagnostic performance of plasma pTau217, pTau181, Aβ1-42 and Aβ1-40 in the LUMIPULSE automated platform for the detection of Alzheimer disease

Alzheimer s Research & Therapy, Год журнала: 2024, Номер 16(1)

Опубликована: Июнь 26, 2024

Abstract Background Recently developed blood markers for Alzheimer's disease (AD) detection have high accuracy but usually require ultra-sensitive analytic tools not commonly available in clinical laboratories, and their performance practice is unknown. Methods We analyzed plasma samples from 290 consecutive participants that underwent lumbar puncture routine a specialized memory clinic (66 cognitively unimpaired, 130 with mild cognitive impairment, 94 dementia). Participants were classified as amyloid positive (A +) or negative (A-) according to CSF Aβ 1–42 /Aβ 1–40 ratio. Plasma pTau 217 , 181 measured the fully-automated LUMIPULSE platform. used linear regression compare biomarkers concentrations between A + A- groups, evaluated Spearman’s correlation performed ROC analyses assess diagnostic detect brain amyloidosis determined by concordance of amyloidosis. Results concentration higher than while ratio was lower compared A-. showed moderate (Rho = 0.66 0.69, respectively). The areas under curve discriminate 0.94 (95% CI 0.92–0.97) 0.88 0.84–0.92) both . Chronic kidney (CKD) related increased biomarker concentrations, ratios less affected. had highest fold change (× 3.2) predictive capability discriminating A-, having 4–7% misclassification rate. global using two-threshold approach robust symptomatic exceeding 90%. Conclusion evaluation on an automated platform exhibited AD pathophysiology, excellent identify sample representing unit.

Язык: Английский

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Head-to-head study of diagnostic accuracy of plasma and cerebrospinal fluid p-tau217 versus p-tau181 and p-tau231 in a memory clinic cohort

Journal of Neurology, Год журнала: 2024, Номер 271(4), С. 2053 - 2066

Опубликована: Янв. 9, 2024

Abstract Background and objective Phosphorylated tau ( p -tau) 217 has recently received attention because it seems more reliable than other -tau variants for identifying Alzheimer’s disease (AD) pathology. Thus, we aimed to compare the diagnostic accuracy of plasma CSF -tau217 with -tau181 -tau231 in a memory clinic cohort. Methods The study included 114 participants (CU = 33; MCI 67; Dementia 14). were correlated versus continuous measures amyloid (A) (T)-PET. phospho-epitopes assessed through: (i) effect sizes δ ) between A ± T groups; (ii) receiver operating characteristic (ROC) analyses A-PET T-PET. Results correlations both T-PET r range 0.64–0.83) stronger those 0.44–0.79) 0.46–0.76). Plasma showed significantly higher differences biomarker groups : 0.55–0.96; 0.51–0.67; 0.53–0.71); ROC curves identify positivity (AUC average 0.96; 0.76; 0.79). On hand, 0.95) did not reveal significant AUC 0.88) 0.89). Discussion demonstrated better performance identification AD pathology clinical phenotypes comparison Furthermore, had comparable CSF. Our findings suggest potential diagnosis screening AD, which could allow decreased use invasive biomarkers future.

Язык: Английский

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Alzheimer disease blood biomarkers: considerations for population-level use

Nature Reviews Neurology, Год журнала: 2024, Номер 20(8), С. 495 - 504

Опубликована: Июнь 11, 2024

Язык: Английский

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