Revised criteria for diagnosis and staging of Alzheimer's disease: Alzheimer's Association Workgroup

Alzheimer s & Dementia, Год журнала: 2024, Номер 20(8), С. 5143 - 5169

Опубликована: Июнь 27, 2024

Abstract The National Institute on Aging and the Alzheimer's Association convened three separate work groups in 2011 single 2012 2018 to create recommendations for diagnosis characterization of disease (AD). present document updates research framework response several recent developments. Defining diseases biologically, rather than based syndromic presentation, has long been standard many areas medicine (e.g., oncology), is becoming a unifying concept common all neurodegenerative diseases, not just AD. consistent with this principle. Our intent objective criteria staging AD, incorporating advances biomarkers, serve as bridge between clinical care. These are intended provide step‐by‐step practice guidelines workflow or specific treatment protocols, but general principles inform AD that reflect current science. Highlights We define (AD) be biological process begins appearance neuropathologic change (ADNPC) while people asymptomatic. Progression burden leads later progression symptoms. Early‐changing Core 1 biomarkers (amyloid positron emission tomography [PET], approved cerebrospinal fluid accurate plasma [especially phosphorylated tau 217]) map onto either amyloid beta tauopathy pathway; however, these presence ADNPC more generally (i.e., both neuritic plaques tangles). An abnormal biomarker result sufficient establish decision making throughout continuum. Later‐changing 2 (biofluid PET) can prognostic information, when abnormal, will increase confidence contributing integrated scheme described accommodates fact copathologies, cognitive reserve, resistance may modify relationships stages.

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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Acceptable performance of blood biomarker tests of amyloid pathology — recommendations from the Global CEO Initiative on Alzheimer’s Disease

Nature Reviews Neurology, Год журнала: 2024, Номер 20(7), С. 426 - 439

Опубликована: Июнь 12, 2024

Anti-amyloid treatments for early symptomatic Alzheimer disease have recently become clinically available in some countries, which has greatly increased the need biomarker confirmation of amyloid pathology. Blood (BBM) tests pathology are more acceptable, accessible and scalable than PET or cerebrospinal fluid (CSF) tests, but highly variable levels performance. The Global CEO Initiative on Alzheimer's Disease convened a BBM Workgroup to consider minimum acceptable performance clinical use. Amyloid status was identified as reference standard. For use triaging test before subsequent confirmatory such CSF recommends that sensitivity ≥90% with specificity ≥85% primary care ≥75–85% secondary depending availability follow-up testing. without should equivalent — ~90%. Importantly, predictive values all vary according pre-test probability must be interpreted complete context. Use meet these standards could enable people receive an accurate timely diagnosis potentially benefit from new treatments. blood offer test. This Consensus Statement provides recommendations

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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Clinical validation of the PrecivityAD2 blood test: A mass spectrometry‐based test with algorithm combining %p‐tau217 and Aβ42/40 ratio to identify presence of brain amyloid

Alzheimer s & Dementia, Год журнала: 2024, Номер 20(5), С. 3179 - 3192

Опубликована: Март 16, 2024

With the availability of disease-modifying therapies for Alzheimer's disease (AD), it is important clinicians to have tests aid in AD diagnosis, especially when presence amyloid pathology a criterion receiving treatment. High-throughput, mass spectrometry-based assays were used measure %p-tau217 and beta (Aβ)42/40 ratio blood samples from 583 individuals with suspected (53% positron emission tomography [PET] positive by Centiloid > 25). An algorithm (PrecivityAD2 test) was developed using these plasma biomarkers identify brain amyloidosis PET. The area under receiver operating characteristic curve (AUC-ROC) (0.94) statistically significantly higher than that p-tau217 concentration (0.91). AUC-ROC PrecivityAD2 test output, Amyloid Probability Score 2, 0.94, yielding 88% agreement Diagnostic performance APS2 similar ethnicity, sex, age, apoE4 status. showed strong clinical validity, excellent

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

Alzheimer s & Dementia, Год журнала: 2024, Номер 20(11), С. 8074 - 8096

Опубликована: Окт. 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.

Язык: Английский

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Blood phosphorylated Tau181 reliably differentiates amyloid‐positive from amyloid‐negative subjects in the Alzheimer's disease continuum: A systematic review and meta‐analysis

Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring, Год журнала: 2025, Номер 17(1)

Опубликована: Янв. 1, 2025

Abstract INTRODUCTION Blood‐based biomarkers seem promising for the diagnosis of Alzheimer's disease (AD). METHODS We performed a systematic review and meta‐analysis on potential blood phosphorylated Tau181 (p‐tau181) to differentiate amyloid‐positive (A+) amyloid‐negative (A−) subjects. Two meta‐analyses were conducted, showing mean p‐tau values in cerebrospinal fluid (CSF) A+ A− group, second comparing concentrations CSF among versus A‐ participants, by laboratory assessment method. RESULTS Eighteen studies (2764 5646 subjects) included. The single‐group showed higher p‐tau181 than group. In head‐to‐head meta‐analysis, reliably differentiated patients from participants. DISCUSSION Regardless technique, differentiates Therefore, it might have important applications early inclusion clinical trials AD patients. Highlights role blood‐based discriminating is still uncertain. Blood distinguishes allow trials.

Язык: Английский

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Artemisinin Alleviates Astrocyte Overactivation and Neuroinflammation by Modulating the IRE1/NF-κB Signaling Pathway in In Vitro and In Vivo Alzheimer's Disease Models

Free Radical Biology and Medicine, Год журнала: 2025, Номер 229, С. 96 - 110

Опубликована: Янв. 16, 2025

Язык: Английский

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