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    Home > Active Ingredient News > Study of Nervous System > Acta Neuropathologica: Plasma p-tau 181 accurately predicts the pathology of Alzheimer's disease and improves the clinical characteristics of cognitive decline at least 8 years before death.

    Acta Neuropathologica: Plasma p-tau 181 accurately predicts the pathology of Alzheimer's disease and improves the clinical characteristics of cognitive decline at least 8 years before death.

    • Last Update: 2020-09-25
    • Source: Internet
    • Author: User
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    Neuropathology of amyloid beta (A beta) plaques and tau nerve fiber tangles (NFT) has been shown to remain the gold standard for the final diagnosis of Alzheimer's disease (AD).
    AD is the most common cause of dementia, accounting for 50-60 per cent of the 50 million reported cases worldwide, and is expected to triple by 2050.
    AD can only be diagnosed through neuropathological tests, i.e. amyloid beta (A beta) plaques and tau nerve fiber tangles (NFT).
    , however, an increasing number of clinical assessments of AD are complemented by neuropathologically proven biomarkers that reflect the pathological characteristics of A-beta and tau, thereby improving the accuracy of diagnosis of AD in life.
    the importance of biomarkers has been highlighted in the recent National Association for Aging and Alzheimer's Disease (NIA-AA) research framework.
    framework, AD is defined as a biological structure that is recorded in the body through an autopsy or biomarker, rather than a clinical syndrome.
    therefore, the term AD is used whenever there is biomarker evidence of A-beta and tau pathology.
    two main types of biomarkers of AD, namely neuroimaging and fluid biomarkers.
    neuroaging biomarkers include PET, which uses a matching body of fiber A beta and a pair of helix tau.
    in liquid biomarkers, cerebrospinal fluid (CSF) biomarkers tantum, widely known as 'core AD biomarkers', widely used in clinical and scientific research.
    , CSF and positive electron emission fault scanning (PET) biomarkers are very helpful in the in vivo diagnosis of AD.
    their accuracy, their widespread implementation is still limited by high costs, limited accessibility and intrusiveness.
    In this paper, the authors' team recently developed a high-performance, ultra-sensitive immunoanalysis method, mainly used to quantify suline-181 phosphate tau (p-tau181) in the plasma, which can identify the pathophysiology of AD with high precision.
    , however, it is not clear whether plasma p-tau181 measured in the years before death was able to predict the final AD pathology diagnosis and successfully separate AD from non-AD dementia pathology.
    we studied a unique cohort study of 115 vertical blood-picking individuals who were clinically evaluated for neuropathology in the first 8, 4 and 2 years at the time of their death.
    that plasma p-tau181 was better associated with AD neuropathology and Braak stages than clinical diagnosis eight years before death.
    we studied a unique queuing study of 115 vertical blood-picking individuals and conducted clinical evaluations eight, four and two years before neuropathological assessment at the time of death.
    results showed that the correlation between plasma p-tau181 and AD neuropathology and Braak stage was better than clinical diagnosis eight years after death.
    In addition, although all patients were diagnosed with AD dementia in their lives, plasma p-tau181 was able to distinguish between AD and non-AD pathology with high accuracy even eight years before death (AUC=97.4%, 95% CI=94.1-100%).
    , the authors' team assessed the longitudinal trajectory of plasma p-tau181 in all patients.
    found that the increase in plasma p-tau181 occurred mainly 8-4 years before the death of patients with AD neuropathy, and then stabilized.
    , non-AD pathology and control groups also showed some increase in expression to death in p-tau181.
    , our study showed that plasma p-tau181 was highly predictive and specific to AD neuropathy in the years before the autopsy.
    data will further support the use of plasma p-tau181 to help with clinical management of primary care and clinical trial recruitment.
    : All participants from DCR were asked to fast for at least 2 hours before medical evaluation.
    blood is extracted and collected into a test tube of sodium acetylene (EDTA).
    the samples (4 degrees C, 2000 x g, 8 minutes) and stored at -80 degrees C within 2 hours of collection.
    the plasma p-tau181 concentration was measured using an ultra-sensitive internal single-molecule array (Simoa) developed by the Clinical Neurochemistry Laboratory of the Department of Psychiatry and Neurochemistry on the HD-X platform (Quanterix, Billerica, MA, USA).
    In short, plasma p-tau181 Simoa analysis consists of paramagnetic beads and specific targeted phosphate suline 181 (AT270, Invitrogen) mice monoclonal capture antibodies and bioclonal detection antibodies (Tau12, biolegen) for the tau N end region.
    immediately before analysis, thaw the plasma sample so that it has eddy currents (2000 l/min) and centrifugation (10 minutes at room temperature 4000 x g), and then dilute twice as much with Tau2.0 buffer.
    plasma samples were randomized and analyzed using the same batch of reagents.
    the plasma p-tau181 data were collected during three analyses, and all samples were measured above the measured quantitative lower limit (1.0 pg/mL).
    as a criterion for determining precision, two quality-controlled plasma samples were analyzed at the beginning and end of each test.
    the two quality control samples in the batch and between batches of variation coefficients are .lt;10%.
    , the study in this paper shows that plasma p-tau181 can predict the pathology of AD, even if the blood samples were obtained a few years before the autopsy.
    have a significant impact on the design of clinical trials and on conventional clinical practice.
    p-tau181 can be used as a fast, cost-effective screening tool for AD treatment trial participants.
    In addition, p-tau181's high accuracy in predicting diagnosed AD neuropathology guides clinicians in accurately diagnosing potential mechanisms (AD pathology, non-AD or hybrid) that lead to cognitive decline, so that treatment and patient management can be managed with greater confidence at an early stage.
    Lantero Rodriguez, J., Karikari, T.K., Suárez-Calvet, M. et al. Plasma p-tau181 accurately predicts Alzheimer's disease pathology at least 8 years prior to post-mortem and improves the clinical characterisation of cognitive decline. Acta Neuropathol 140, 267-278 (2020). Source: MedSci Originals !-- Content Presentation Ends -- !-- To Determine If Login Ends.
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