The Alzheimer's Association appropriate use recommendations for blood biomarkers in Alzheimer's disease

Alzheimer s & Dementia, Год журнала: 2022, Номер 18(12), С. 2669 - 2686

Опубликована: Июль 31, 2022

Abstract Blood‐based markers (BBMs) have recently shown promise to revolutionize the diagnostic and prognostic work‐up of Alzheimer's disease (AD), as well improve design interventional trials. Here we discuss in detail further research needed be performed before widespread use BBMs. We already now recommend BBMs (pre‐)screeners identify individuals likely AD pathological changes for inclusion trials evaluating disease‐modifying therapies, provided status is confirmed with positron emission tomography (PET) or cerebrospinal fluid (CSF) testing. also encourage studying longitudinal BBM ongoing future However, should not yet used primary endpoints pivotal Further, cautiously start using specialized memory clinics part patients cognitive symptoms results whenever possible CSF PET. Additional data are stand‐alone markers, considering care.

Язык: Английский

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Differential roles of Aβ42/40, p-tau231 and p-tau217 for Alzheimer’s trial selection and disease monitoring

Nature Medicine, Год журнала: 2022, Номер 28(12), С. 2555 - 2562

Опубликована: Дек. 1, 2022

Abstract Blood biomarkers indicative of Alzheimer’s disease (AD) pathology are altered in both preclinical and symptomatic stages the disease. Distinctive may be optimal for identification AD or monitoring progression. that correlate with changes cognition atrophy during course could used clinical trials to identify successful interventions thereby accelerate development efficient therapies. When disease-modifying treatments become approved use, blood-based might also inform on treatment implementation management practice. In BioFINDER-1 cohort, plasma phosphorylated (p)-tau231 amyloid-β42/40 ratio were more changed at lower thresholds amyloid pathology. Longitudinally, however, only p-tau217 demonstrated marked amyloid-dependent over 4–6 years disease, no such observed p-tau231, p-tau181, amyloid-β42/40, glial acidic fibrillary protein neurofilament light. Only longitudinal increases associated deterioration brain AD. The selective increase its associations cognitive decline was confirmed an independent cohort (Wisconsin Registry Prevention). These findings support differential association strongly highlight as a surrogate marker progression prodromal AD, impact new treatments.

Язык: Английский

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Synaptic degeneration in Alzheimer disease

Nature Reviews Neurology, Год журнала: 2022, Номер 19(1), С. 19 - 38

Опубликована: Дек. 13, 2022

Язык: Английский

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Diagnostic Accuracy of a Plasma Phosphorylated Tau 217 Immunoassay for Alzheimer Disease Pathology

JAMA Neurology, Год журнала: 2024, Номер 81(3), С. 255 - 255

Опубликована: Янв. 22, 2024

Importance Phosphorylated tau (p-tau) is a specific blood biomarker for Alzheimer disease (AD) pathology, with p-tau217 considered to have the most utility. However, availability of tests research and clinical use has been limited. Expanding access this highly accurate AD crucial wider evaluation implementation tests. Objective To determine utility novel commercially available immunoassay plasma detect pathology evaluate reference ranges abnormal amyloid β (Aβ) longitudinal change across 3 selected cohorts. Design, Setting, Participants This cohort study examined data from single-center observational cohorts: cross-sectional Translational Biomarkers in Aging Dementia (TRIAD) (visits October 2017–August 2021) Wisconsin Registry Alzheimer’s Prevention (WRAP) February 2007–November 2020) Sant Pau Initiative on Neurodegeneration (SPIN) (baseline visits March 2009–November 2021). included individuals without cognitive impairment grouped by (AT) status using PET or CSF biomarkers. Data were analyzed June 2023. Exposures Magnetic resonance imaging, Aβ positron emission tomography (PET), PET, cerebrospinal fluid (CSF) biomarkers (Aβ42/40 p-tau immunoassays), (ALZpath pTau217 assay). Main Outcomes Measures Accuracy detecting according baseline status. Results The 786 participants (mean [SD] age, 66.3 [9.7] years; 504 females [64.1%] 282 males [35.9%]). High accuracy was observed identifying elevated (area under curve [AUC], 0.92-0.96; 95% CI, 0.89-0.99) (AUC, 0.93-0.97; 0.84-0.99) all These accuracies comparable determining signal. detection 3-range yielded reproducible results reduced confirmatory testing approximately 80%. Longitudinally, values showed an annual increase only Aβ-positive individuals, highest those positivity. Conclusions Relevance found that accurately identified biological AD, biomarkers, cut-offs It detected changes, including at preclinical stage.

Язык: Английский

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Plasma p-tau231 and p-tau217 as state markers of amyloid-β pathology in preclinical Alzheimer’s disease

Nature Medicine, Год журнала: 2022, Номер unknown

Опубликована: Авг. 11, 2022

Abstract Blood biomarkers indicating elevated amyloid-β (Aβ) pathology in preclinical Alzheimer’s disease are needed to facilitate the initial screening process of participants disease-modifying trials. Previous biofluid data suggest that phosphorylated tau231 (p-tau231) could indicate incipient Aβ pathology, but a comprehensive comparison with other putative blood is lacking. In ALFA+ cohort, all tested plasma (p-tau181, p-tau217, p-tau231, GFAP, NfL and Aβ42/40) were significantly changed disease. However, p-tau231 reached abnormal levels lowest burden. Plasma p-tau217 had strongest association positron emission tomography (PET) retention early accumulating regions associated longitudinal increases PET uptake individuals without overt at baseline. summary, better capture earliest cerebral changes, before plaque present, promising enrich population for clinical

Язык: Английский

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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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Astrocyte reactivity influences amyloid-β effects on tau pathology in preclinical Alzheimer’s disease

Nature Medicine, Год журнала: 2023, Номер 29(7), С. 1775 - 1781

Опубликована: Май 29, 2023

Abstract An unresolved question for the understanding of Alzheimer’s disease (AD) pathophysiology is why a significant percentage amyloid-β (Aβ)-positive cognitively unimpaired (CU) individuals do not develop detectable downstream tau pathology and, consequently, clinical deterioration. In vitro evidence suggests that reactive astrocytes unleash Aβ effects in pathological phosphorylation. Here, biomarker study across three cohorts ( n = 1,016), we tested whether astrocyte reactivity modulates association with phosphorylation CU individuals. We found was associated increased plasma phosphorylated only positive (Ast + ). Cross-sectional and longitudinal tau–positron emission tomography analyses revealed an AD-like pattern tangle accumulation as function Ast Our findings suggest important upstream event linking initial pathology, which may have implications biological definition preclinical AD selecting trials.

Язык: Английский

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Association of Donanemab Treatment With Exploratory Plasma Biomarkers in Early Symptomatic Alzheimer Disease

JAMA Neurology, Год журнала: 2022, Номер 79(12), С. 1250 - 1250

Опубликована: Окт. 17, 2022

Importance Plasma biomarkers of Alzheimer disease may be useful as minimally invasive pharmacodynamic measures treatment outcomes. Objective To analyze the association donanemab with plasma associated disease. Design, Setting, and Participants TRAILBLAZER-ALZ was a randomized, double-blind, placebo-controlled clinical trial conducted from December 18, 2017, to 4, 2020, across 56 sites in US Canada. Exploratory were prespecified post hoc addition glial fibrillary acidic protein amyloid-β. Men women aged 60 85 years gradual progressive change memory function for at least 6 months included. A total 1955 participants assessed eligibility. Key eligibility criteria include Mini-Mental State Examination scores 20 28 elevated amyloid intermediate tau levels. Interventions Randomized received or placebo every 4 weeks up 72 weeks. The first 3 doses given 700 mg then increased 1400 blinded dose reductions specified based on reduction. Main Outcomes Measures Change biomarker levels after treatment. Results In TRAILBLAZER-ALZ, 272 (mean [SD] age, 75.2 [5.5] years; 145 [53.3%] female) randomized. phosphorylated 217 (pTau ) significantly lower compared early 12 start (least square mean difference vs placebo, –0.04 [95% CI, –0.07 –0.02]; P = .002 –0.01]; .01, respectively). No significant differences amyloid-β 42/40 neurofilament light chain observed between arms end Changes pTau correlated Centiloid percent (Spearman rank correlation coefficient [ R ] 0.484 0.359-0.592]; < .001 0.453 0.306-0.579]; .001, respectively) following Additionally, baseline ( 0.399 0.278-0.508], 0.393 0.254-0.517]; Conclusions Relevance Significant patients symptomatic These easily accessible might provide additional evidence pathology through anti-amyloid therapy. Usefulness assessing response will require further evaluation. Trial Registration ClinicalTrials.gov Identifier: NCT03367403

Язык: Английский

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Plasma Aβ42/40 ratio, p‐tau181, GFAP, and NfL across the Alzheimer's disease continuum: A cross‐sectional and longitudinal study in the AIBL cohort

Alzheimer s & Dementia, Год журнала: 2022, Номер 19(4), С. 1117 - 1134

Опубликована: Июль 21, 2022

Plasma amyloid beta (Aβ)1-42/Aβ1-40 ratio, phosphorylated-tau181 (p-tau181), glial fibrillary acidic protein (GFAP), and neurofilament light (NfL) are putative blood biomarkers for Alzheimer's disease (AD). However, head-to-head cross-sectional longitudinal comparisons of the aforementioned across AD continuum lacking.Plasma Aβ1-42, Aβ1-40, p-tau181, GFAP, NfL were measured utilizing Single Molecule Array (Simoa) platform compared cross-sectionally continuum, wherein Aβ-PET (positron emission tomography)-negative cognitively unimpaired (CU Aβ-, n = 81) mild cognitive impairment (MCI 26) participants with Aβ-PET-positive Aβ+, 39; MCI 33; 46) from Australian Imaging, Biomarker & Lifestyle Flagship Study Ageing (AIBL) cohort. Longitudinal plasma biomarker changes also assessed in (n 27) 29) CU 120) participants. In addition, associations between baseline levels prospective decline load over a 7 to 10-year duration.Lower Aβ1-42/Aβ1-40 ratio elevated p-tau181 GFAP observed whereas was Aβ+ Aβ- Aβ-. Among biomarkers, models without risk factors (age, sex, apolipoprotein E (APOE) ε4 carrier status), performed equivalent or better than other predicting brain Aβ-/+ status continuum. factors, panel Aβ1-42/Aβ1-40, any alone Longitudinally, altered CU, CU. lower higher associated increased prospectively.These findings suggest that longitudinally, along prospectively load. although an may have superior predictive capability continuum.Area under curve (AUC) ≥ AUC Aβ42/40, PET (Aβ-/+). Aβ42/40+p-tau181+GFAP Aβ42/40/p-tau181/GFAP/NfL Aβ-/+. versus decline. Aβ prospectively.

Язык: Английский

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Plasma and CSF biomarkers in a memory clinic: Head‐to‐head comparison of phosphorylated tau immunoassays

Alzheimer s & Dementia, Год журнала: 2022, Номер 19(5), С. 1913 - 1924

Опубликована: Ноя. 12, 2022

Abstract Introduction Direct comparisons of the main blood phosphorylated tau immunoassays in memory clinic populations are needed to understand possible differences. Methods In BIODEGMAR study, 197 participants presenting with cognitive complaints were classified into an Alzheimer's disease (AD) or a non‐AD cerebrospinal fluid (CSF) profile group, according their amyloid beta 42/ (Aβ42/p‐tau) ratio. We performed head‐to‐head comparison nine plasma and CSF determined accuracy discriminate abnormal Aβ42/p‐tau Results All studied biomarkers significantly higher AD group compared discriminated For p‐tau biomarkers, discrimination was shown by Janssen p‐tau217 ( r = 0.76; area under curve [AUC] 0.96), ADx p‐tau181 0.73; AUC 0.94), Lilly 0.94). Discussion Several can be used specialized as stand‐alone biomarker detect biologically‐defined AD. Highlights Patients (AD CSF) have (p‐tau) levels than group. patients from p‐tau217, p‐tau181, show highest biologically defined UGot p‐tau231 performances that comparable counterparts.

Язык: Английский

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