A two-step workflow based on plasma p-tau217 to screen for amyloid β positivity with further confirmatory testing only in uncertain cases DOI Creative Commons
Wagner S. Brum, Nicholas Cullen,

Shorena Janelidze

и другие.

Nature Aging, Год журнала: 2023, Номер 3(9), С. 1079 - 1090

Опубликована: Авг. 31, 2023

Cost-effective strategies for identifying amyloid-β (Aβ) positivity in patients with cognitive impairment are urgently needed recent approvals of anti-Aβ immunotherapies Alzheimer's disease (AD). Blood biomarkers can accurately detect AD pathology, but it is unclear whether their incorporation into a full diagnostic workflow reduce the number confirmatory cerebrospinal fluid (CSF) or positron emission tomography (PET) tests while classifying patients. We evaluated two-step determining Aβ-PET status mild (MCI) from two independent memory clinic-based cohorts (n = 348). A blood-based model including plasma tau protein 217 (p-tau217), age and APOE ε4 was developed BioFINDER-1 (area under curve (AUC) 89.3%) validated BioFINDER-2 (AUC 94.3%). In step 1, used to stratify low, intermediate high risk positivity. 2, we assumed referral only intermediate-risk CSF Aβ42/Aβ40 testing, whereas 1 alone determined Aβ-status low- high-risk groups. Depending on lenient, moderate stringent thresholds were overall accuracy detecting 88.2%, 90.5% 92.0%, respectively, reducing necessary by 85.9%, 72.7% 61.2%, respectively. secondary analyses, an adapted version led successful validation different p-tau217 immunoassay TRIAD cohort 84). conclusion, using p-tau217-based stratification MCI substantially need testing patients, offering cost-effective strategy clinic settings.

Язык: Английский

Lecanemab in Early Alzheimer’s Disease DOI Open Access
Christopher H. van Dyck,

Chad J. Swanson,

Paul Aisen

и другие.

New England Journal of Medicine, Год журнала: 2022, Номер 388(1), С. 9 - 21

Опубликована: Ноя. 30, 2022

The accumulation of soluble and insoluble aggregated amyloid-beta (Aβ) may initiate or potentiate pathologic processes in Alzheimer's disease. Lecanemab, a humanized IgG1 monoclonal antibody that binds with high affinity to Aβ protofibrils, is being tested persons early

Язык: Английский

Процитировано

2752
Donanemab in Early Symptomatic Alzheimer Disease DOI Open Access

John R. Sims,

Jennifer A. Zimmer,

Cynthia Evans

и другие.

JAMA, Год журнала: 2023, Номер 330(6), С. 512 - 512

Опубликована: Июль 17, 2023

Importance There are limited efficacious treatments for Alzheimer disease. Objective To assess efficacy and adverse events of donanemab, an antibody designed to clear brain amyloid plaque. Design, Setting, Participants Multicenter (277 medical research centers/hospitals in 8 countries), randomized, double-blind, placebo-controlled, 18-month phase 3 trial that enrolled 1736 participants with early symptomatic disease (mild cognitive impairment/mild dementia) low/medium or high tau pathology based on positron emission tomography imaging from June 2020 November 2021 (last patient visit primary outcome April 2023). Interventions were randomized a 1:1 ratio receive donanemab (n = 860) placebo 876) intravenously every 4 weeks 72 weeks. the group switched blinded manner if dose completion criteria met. Main Outcomes Measures The was change integrated Disease Rating Scale (iADRS) score baseline 76 (range, 0-144; lower scores indicate greater impairment). 24 gated outcomes (primary, secondary, exploratory), including secondary sum boxes Clinical Dementia (CDR-SB) 0-18; higher Statistical testing allocated α .04 population outcomes, remainder (.01) combined outcomes. Results Among (mean age, 73.0 years; 996 [57.4%] women; 1182 [68.1%] 552 [31.8%] pathology), 1320 (76%) completed trial. Of 23 statistically significant. least-squares mean (LSM) iADRS at −6.02 (95% CI, −7.01 −5.03) −9.27 −10.23 −8.31) (difference, 3.25 [95% 1.88-4.62]; P < .001) −10.2 −11.22 −9.16) −13.1 −14.10 −12.13) 2.92 1.51-4.33]; population. LSM CDR-SB 1.20 1.00-1.41) 1.88 1.68-2.08) −0.67 −0.95 −0.40]; 1.72 1.53-1.91) 2.42 2.24-2.60) −0.7 −0.45]; Amyloid-related abnormalities edema effusion occurred 205 (24.0%; 52 symptomatic) 18 (2.1%; 0 during study) infusion-related reactions 74 (8.7%) (0.5%) placebo. Three deaths 1 considered treatment related. Conclusions Relevance pathology, significantly slowed clinical progression those Trial Registration ClinicalTrials.gov Identifier: NCT04437511

Язык: Английский

Процитировано

1130
Dementia prevention, intervention, and care: 2024 report of the Lancet standing Commission DOI
Gill Livingston, Jonathan Huntley, Kathy Liu

и другие.

The Lancet, Год журнала: 2024, Номер 404(10452), С. 572 - 628

Опубликована: Июль 31, 2024

Язык: Английский

Процитировано

540
Role of neuroinflammation in neurodegeneration development DOI Creative Commons
Weifeng Zhang, Dan Xiao, Qinwen Mao

и другие.

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Июль 12, 2023

Abstract Studies in neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease and Amyotrophic lateral sclerosis, Huntington’s so on, have suggested that inflammation is not only a result of neurodegeneration but also crucial player this process. Protein aggregates which are very common pathological phenomenon can induce neuroinflammation further aggravates protein aggregation neurodegeneration. Actually, even happens earlier than aggregation. Neuroinflammation induced by genetic variations CNS cells or peripheral immune may deposition some susceptible population. Numerous signaling pathways range been to be involved the pathogenesis neurodegeneration, although they still far from being completely understood. Due limited success traditional treatment methods, blocking enhancing inflammatory considered promising strategies for therapy many them got exciting results animal models clinical trials. Some them, few, approved FDA usage. Here we comprehensively review factors affecting major pathogenicity sclerosis. We summarize current strategies, both clinic, diseases.

Язык: Английский

Процитировано

522
Revised criteria for diagnosis and staging of Alzheimer's disease: Alzheimer's Association Workgroup DOI Creative Commons
Clifford R. Jack,

J. Scott Andrews,

Thomas G. Beach

и другие.

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

Процитировано

464
The Alzheimer's Association appropriate use recommendations for blood biomarkers in Alzheimer's disease DOI Creative Commons
Oskar Hansson, Rebecca M. Edelmayer, Adam L. Boxer

и другие.

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

Процитировано

361
Alzheimer's disease drug development pipeline: 2023 DOI Creative Commons
Jeffrey L. Cummings, Yadi Zhou, Garam Lee

и другие.

Alzheimer s & Dementia Translational Research & Clinical Interventions, Год журнала: 2023, Номер 9(2)

Опубликована: Апрель 1, 2023

Drugs that prevent the onset, slow progression, or improve cognitive and behavioral symptoms of Alzheimer's disease (AD) are needed.

Язык: Английский

Процитировано

325
Blood biomarkers for Alzheimer’s disease in clinical practice and trials DOI
Oskar Hansson, Kaj Blennow,

Henrik Zetterberg

и другие.

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

Опубликована: Май 18, 2023

Язык: Английский

Процитировано

213
Emerging diagnostics and therapeutics for Alzheimer disease DOI
Wade Self, David M. Holtzman

Nature Medicine, Год журнала: 2023, Номер 29(9), С. 2187 - 2199

Опубликована: Сен. 1, 2023

Язык: Английский

Процитировано

183
Trial of Solanezumab in Preclinical Alzheimer’s Disease DOI
Reisa A. Sperling, Michael Donohue, Rema Raman

и другие.

New England Journal of Medicine, Год журнала: 2023, Номер 389(12), С. 1096 - 1107

Опубликована: Июль 17, 2023

Trials of monoclonal antibodies that target various forms amyloid at different stages Alzheimer's disease have had mixed results. Download a PDF the Research Summary. We tested solanezumab, which targets monomeric amyloid, in phase 3 trial involving persons with preclinical disease. Persons 65 to 85 years age global Clinical Dementia Rating score 0 (range, 3, indicating no cognitive impairment and severe dementia), on Mini–Mental State Examination 25 or more 30, lower scores poorer cognition), elevated brain levels 18F-florbetapir positron-emission tomography (PET) were enrolled. Participants randomly assigned 1:1 ratio receive solanezumab dose up 1600 mg intravenously every 4 weeks placebo. The primary end point was change Preclinical Alzheimer Cognitive Composite (PACC) (calculated as sum four z scores, higher better performance) over period 240 weeks. A total 1169 underwent randomization: 578 group 591 placebo group. mean participants 72 years, approximately 60% women, 75% family history dementia. At weeks, PACC −1.43 −1.13 (difference, −0.30; 95% confidence interval, −0.82 0.22; P=0.26). Amyloid PET increased by 11.6 centiloids 19.3 Amyloid-related imaging abnormalities (ARIA) edema occurred less than 1% each ARIA microhemorrhage hemosiderosis 29.2% 32.8% those Solanezumab, levels, did not slow decline compared (Funded National Institute Aging others; A4 ClinicalTrials.gov number, NCT02008357.) QUICK TAKE VIDEO SUMMARYSolanezumab Disease 02:05

Язык: Английский

Процитировано

175