Blood Biomarkers to Detect Alzheimer Disease in Primary Care and Secondary Care

JAMA, Год журнала: 2024, Номер 332(15), С. 1245 - 1245

Опубликована: Июль 28, 2024

Importance An accurate blood test for Alzheimer disease (AD) could streamline the diagnostic workup and treatment of AD. Objective To prospectively evaluate a clinically available AD in primary care secondary using predefined biomarker cutoff values. Design, Setting, Participants There were 1213 patients undergoing clinical evaluation due to cognitive symptoms who examined between February 2020 January 2024 Sweden. The values had been established an independent cohort applied (n = 307) 300); 1 plasma sample per patient was analyzed as part single batch each cohort. then evaluated 208) 398); sent analysis within 2 weeks collection. Exposure Blood tests based on analyses by mass spectrometry determine ratio phosphorylated tau 217 (p-tau217) non–p-tau217 (expressed percentage p-tau217) alone when combined with amyloid-β 42 40 (Aβ42:Aβ40) (the amyloid probability score [APS2]). Main Outcomes Measures outcome pathology (determined abnormal cerebrospinal fluid Aβ42:Aβ40 p-tau217). positive predictive value (PPV), negative (NPV), accuracy, area under curve (AUC) calculated. Results mean age 74.2 years (SD, 8.3 years), 48% women, 23% subjective decline, 44% mild impairment, 33% dementia. In both assessments, 50% pathology. When samples cohort, AUC 0.97 (95% CI, 0.95-0.99) APS2 used, PPV 91% 87%-96%), NPV 92% 87%-96%); 0.96 0.94-0.98) 88% 83%-93%), 87% 82%-93%). (biweekly) 81%-94%), 90% 84%-96%); 0.95-0.98) 87%-95%), 87%-95%). accuracy high 4 cohorts (range, 88%-92%). Primary physicians 61% 53%-69%) identifying after examination, testing, computed tomographic scan vs 86%-96%) APS2. Dementia specialists 73% 68%-79%) 88%-95%) overall population, (90% [95% 88%-92%]) not different from p-tau217 88%-91%]). Conclusions Relevance among individuals Future studies should how use these biomarkers influences care.

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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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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Alzheimer’s disease: insights into pathology, molecular mechanisms, and therapy

Protein & Cell, Год журнала: 2024, Номер unknown

Опубликована: Май 11, 2024

Abstract Alzheimer’s disease (AD), the leading cause of dementia, is characterized by accumulation amyloid plaques and neurofibrillary tangles in brain. This condition casts a significant shadow on global health due to its complex multifactorial nature. In addition genetic predispositions, development AD influenced myriad risk factors, including aging, systemic inflammation, chronic conditions, lifestyle, environmental exposures. Recent advancements understanding pathophysiology are paving way for enhanced diagnostic techniques, improved assessment, potentially effective prevention strategies. These discoveries crucial quest unravel complexities AD, offering beacon hope management treatment options millions affected this debilitating disease.

Язык: Английский

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Plasma Phosphorylated Tau 217 and Aβ42/40 to Predict Early Brain Aβ Accumulation in People Without Cognitive Impairment

JAMA Neurology, Год журнала: 2024, Номер 81(9), С. 947 - 947

Опубликована: Июль 28, 2024

Importance Phase 3 trials of successful antiamyloid therapies in Alzheimer disease (AD) have demonstrated improved clinical efficacy people with less severe disease. Plasma biomarkers will be essential for efficient screening participants future primary prevention testing cognitively unimpaired (CU) individuals initially low brain β-amyloid (Aβ) levels who are at high risk accumulating Aβ. Objective To investigate if combining plasma could useful predicting subsequent development Aβ pathology CU subthreshold (defined as <40 Centiloids) baseline. Design, Setting, and Participants This was a longitudinal study including Swedish BioFINDER-2 (enrollment 2017-2022) replication 2 independent cohorts, the Knight Disease Research Center (Knight ADRC; enrollment 1988 2019) BioFINDER-1 2009-2015). Included analysis convenience sample baseline phosphorylated tau 217 (p-tau217) Aβ42/40 assessments positron emission tomography (Aβ-PET) or cerebrospinal fluid (CSF) Aβ42/40. Data were analyzed between April 2023 May 2024. Exposures Baseline Aβ42/40, p-tau217, ratio p-tau217 to nonphosphorylated (%p-tau217), p-tau231, glial fibrillary acidic protein (GFAP). Main Outcomes Measures Cross-sectional PET CSF measures pathology. Results included 495 (BioFINDER-2), 283 ADRC), 205 (BioFINDER-1) participants. In BioFINDER-2, mean (SD) age 65.7 (14.4) 261 females (52.7%). When detecting abnormal Aβ-status, combination %p-tau217 showed better performance (area under curve = 0.949; 95% CI, 0.929-0.970; P <.02) than individual biomarkers. Aβ-PET, significantly associated Aβ-PET (n 384) increases over time 224). Associations their interaction (%p-tau217: β 2.77; 1.84-3.70; Aβ42/40: −1.64; −2.53 −0.75; × −2.14; −2.79 −1.49; < .001) 0.67; 0.48-0.87; −0.33; −0.51 −0.15; −0.31; −0.44 −0.18; also significant models predictors. Similarly, independently ADRC 0.71; 0.26-1.16; .002; −0.74; −1.26 −0.22; .006) (p-tau217: −0.0003; −0.0004 −0.0001; .01; 0.0004; 0.0002-0.0006; p-tau231 GFAP did not provide any clear value. Conclusions Relevance this cohort suggest that p-tau217and early stages accumulation. These might thus facilitate trials.

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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Misfolding and aggregation in neurodegenerative diseases: protein quality control machinery as potential therapeutic clearance pathways

Cell Communication and Signaling, Год журнала: 2024, Номер 22(1)

Опубликована: Авг. 30, 2024

The primary challenge in today's world of neuroscience is the search for new therapeutic possibilities neurodegenerative disease. Central to these disorders lies among other factors, aberrant folding, aggregation, and accumulation proteins, resulting formation toxic entities that contribute neuronal degeneration. This review concentrates on key proteins such as β-amyloid (Aβ), tau, α-synuclein, elucidating intricate molecular events underlying their misfolding aggregation. We critically evaluate mechanisms governing elimination misfolded shedding light potential strategies. specifically examine pathways endoplasmic reticulum (ER) unfolded protein response (UPR), chaperones, chaperone-mediated autophagy (CMA), intersecting signaling Keap1-Nrf2-ARE, along with connected through p62. Above all, we emphasize significance quality control mechanisms, encompassing interventions targeting regulation post-translational modifications, enhancement chaperones clearance. Additionally, focus current new, multi-target approaches. In conclusion, this systematically consolidates insights into emerging strategies predicated aggregates

Язык: Английский

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Aggregation-Induced Emission Luminogen: Role in Biopsy for Precision Medicine

Chemical Reviews, Год журнала: 2024, Номер 124(20), С. 11242 - 11347

Опубликована: Окт. 9, 2024

Biopsy, including tissue and liquid biopsy, offers comprehensive real-time physiological pathological information for disease detection, diagnosis, monitoring. Fluorescent probes are frequently selected to obtain adequate on processes in a rapid minimally invasive manner based their advantages biopsy. However, conventional fluorescent have been found show aggregation-caused quenching (ACQ) properties, impeding greater progresses this area. Since the discovery of aggregation-induced emission luminogen (AIEgen) promoted advancements molecular bionanomaterials owing unique high quantum yield (QY) signal-to-noise ratio (SNR),

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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Lecanemab approval in EU: what should we be ready for?– the EANM perspective

European Journal of Nuclear Medicine and Molecular Imaging, Год журнала: 2025, Номер unknown

Опубликована: Янв. 10, 2025

Язык: Английский

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