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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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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Emerging diagnostics and therapeutics for Alzheimer disease

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

Опубликована: Сен. 1, 2023

Язык: Английский

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Lecanemab in patients with early Alzheimer’s disease: detailed results on biomarker, cognitive, and clinical effects from the randomized and open-label extension of the phase 2 proof-of-concept study

Alzheimer s Research & Therapy, Год журнала: 2022, Номер 14(1)

Опубликована: Дек. 21, 2022

Abstract Background Lecanemab, a humanized IgG1 monoclonal antibody that targets soluble aggregated Aβ species (protofibrils), has demonstrated robust brain fibrillar amyloid reduction and slowing of clinical decline in early AD. The objective this analysis is to report results from study 201 blinded period (core), the open-label extension (OLE), gap (between core OLE) supporting effectiveness lecanemab. Methods lecanemab was double-blind, randomized, placebo-controlled 856 patients randomized one five dose regimens or placebo. An OLE initiated allow receive 10mg/kg biweekly for up 24 months, with an intervening off-treatment (gap period) ranging 9 59 months (mean months). Results At 12 18 treatment core, 10 mg/kg dose-dependent reductions measured PET corresponding changes plasma biomarkers cognitive decline. rates progression during were similar placebo subjects, differences maintained after discontinued dosing over average period. During gap, Aβ42/40 ratio p-tau181 levels began return towards pre-randomization more quickly than PET. baseline, vs at across 3 assessments. In OLE, produced SUVr, improvements ratio, p-tau181. Conclusions Lecanemab resulted significant plaques Data indicate rapid pronounced correlates benefit potential disease-modifying effects, as well use monitor effects. Trial registration ClinicalTrials.gov NCT01767311 .

Язык: Английский

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Cerebrospinal fluid proteomics define the natural history of autosomal dominant Alzheimer’s disease

Nature Medicine, Год журнала: 2023, Номер 29(8), С. 1979 - 1988

Опубликована: Авг. 1, 2023

Abstract Alzheimer’s disease (AD) pathology develops many years before the onset of cognitive symptoms. Two pathological processes—aggregation amyloid-β (Aβ) peptide into plaques and microtubule protein tau neurofibrillary tangles (NFTs)—are hallmarks disease. However, other brain processes are thought to be key mediators Aβ plaque NFT pathology. How these additional pathologies evolve over course is currently unknown. Here we show that proteomic measurements in autosomal dominant AD cerebrospinal fluid (CSF) linked coexpression can used characterize evolution a timescale spanning six decades. SMOC1 SPON1 proteins associated with were elevated CSF nearly 30 symptoms, followed by changes synaptic proteins, metabolic axonal inflammatory finally decreases neurosecretory proteins. The proteome discriminated mutation carriers from noncarriers symptom as well or better than measures. Our results highlight multifaceted landscape pathophysiology its temporal evolution. Such knowledge will critical for developing precision therapeutic interventions biomarkers beyond those tau.

Язык: Английский

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The performance of plasma amyloid beta measurements in identifying amyloid plaques in Alzheimer’s disease: a literature review

Alzheimer s Research & Therapy, Год журнала: 2022, Номер 14(1)

Опубликована: Дек. 27, 2022

Abstract The extracellular buildup of amyloid beta (Aβ) plaques in the brain is a hallmark Alzheimer’s disease (AD). Detection Aβ pathology essential for AD diagnosis and identifying recruiting research participants clinical trials evaluating disease-modifying therapies. Currently, diagnoses are usually made by assessments, although detection with positron emission tomography (PET) scans or cerebrospinal fluid (CSF) analysis can be used specialty clinics. These measures aggregation, e.g. plaques, protofibrils, oligomers, medically invasive often only available at specialized medical centers not covered insurance, PET costly. Therefore, major goal recent years has been to identify blood-based biomarkers that accurately detect cost-effective, minimally procedures. To assess performance plasma assays predicting burden central nervous system (CNS), this review compares twenty-one different manuscripts measurements 42 40 amino acid-long (Aβ42 Aβ40) predict CNS status. Methodologies quantitate Aβ42 peptides blood via immunoassay immunoprecipitation-mass spectrometry (IP-MS) were considered, their ability distinguish amyloidosis compared CSF as reference standards was evaluated. Recent studies indicate some IP-MS perform well precisely measuring detecting aggregates.

Язык: Английский

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Increasing participant diversity in AD research: Plans for digital screening, blood testing, and a community‐engaged approach in the Alzheimer's Disease Neuroimaging Initiative 4

Alzheimer s & Dementia, Год журнала: 2022, Номер 19(1), С. 307 - 317

Опубликована: Окт. 9, 2022

Abstract Introduction The Alzheimer's Disease Neuroimaging Initiative (ADNI) aims to validate biomarkers for disease (AD) clinical trials. To improve generalizability, ADNI4 enroll 50‐60% of its new participants from underrepresented populations (URPs) using biofluid and digital technologies. has received funding the National Institute on Aging beginning September 2022. Methods will recruit URPs community‐engaged approaches. An online portal screen 20,000 participants, 4000 whom (50‐60% URPs) be tested plasma APOE . From this, 500 undergo in‐clinic assessment joining ADNI3 rollover participants. Remaining (∼3500) longitudinal cognitive testing. add MRI sequences PET tracers. Project 1 optimize in AD Results Discussion generalizability results, use remote blood screening, continue providing clinical, biomarker, autopsy data investigators.

Язык: Английский

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Blood Biomarkers from Research Use to Clinical Practice: What Must Be Done? A Report from the EU/US CTAD Task Force

The Journal of Prevention of Alzheimer s Disease, Год журнала: 2022, Номер unknown

Опубликована: Янв. 1, 2022

Язык: Английский

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Plasma Biomarkers of Alzheimer’s Disease: A Review of Available Assays, Recent Developments, and Implications for Clinical Practice

Journal of Alzheimer s Disease Reports, Год журнала: 2023, Номер 7(1), С. 355 - 380

Опубликована: Апрель 25, 2023

Recently, low-sensitive plasma assays have been replaced by new ultra-sensitive such as single molecule enzyme-linked immunosorbent assay (Simoa), the Mesoscale Discovery (MSD) platform, and immunoprecipitation-mass spectrometry (IP-MS) with higher accuracy in determination of biomarkers Alzheimer's disease (AD). Despite significant variability, many studies established in-house cut-off values for most promising available biomarkers. We first reviewed used laboratory methods to measure AD Next, we review focused on diagnostic performance these identify cases, predict cognitive decline pre-clinical differentiate cases from other dementia. summarized data published until January 2023. A combination Aβ42/40 ratio, age, APOE status showed best diagnosing brain amyloidosis a liquid chromatography-mass (LC-MS) assay. Plasma p-tau217 has shown distinguishing Aβ-PET+ Aβ-PET-even cognitively unimpaired individuals. also different each biomarker when available. Recently developed undeniable importance research, improved analytical performance. Some extensively clinical trials are now clinically Nonetheless, several challenges remain their widespread use practice.

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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