Plasma phospho-tau in Alzheimer’s disease: towards diagnostic and therapeutic trial applications

Molecular Neurodegeneration, Journal Year: 2023, Volume and Issue: 18(1)

Published: March 16, 2023

As the leading cause of dementia, Alzheimer's disease (AD) is a major burden on affected individuals, their families and caregivers, healthcare systems. Although AD can be identified diagnosed by cerebrospinal fluid or neuroimaging biomarkers that concord with neuropathological evidence clinical symptoms, challenges regarding practicality accessibility hinder widespread availability implementation. Consequently, many people suspected cognitive impairment due to do not receive biomarker-supported diagnosis. Blood have capacity help expand access diagnostics worldwide. One such promising biomarker plasma phosphorylated tau (p-tau), which has demonstrated specificity versus non-AD neurodegenerative diseases, will extremely important inform diagnosis eligibility for therapies recently been approved. This review provides an update diagnostic prognostic performances p-tau181, p-tau217 p-tau231, associations in vivo autopsy-verified pathological hallmarks. Additionally, we discuss potential applications unanswered questions p-tau therapeutic trials, given recent addition toolbox participant screening, recruitment during-trial monitoring. Outstanding include assay standardization, threshold generation verification diverse cohorts reflective wider community attending memory clinics included trials.

Language: Английский

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Designing the next-generation clinical care pathway for Alzheimer’s disease

Nature Aging, Journal Year: 2022, Volume and Issue: 2(8), P. 692 - 703

Published: Aug. 19, 2022

Language: Английский

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Predicting amyloid PET and tau PET stages with plasma biomarkers

Brain, Journal Year: 2023, Volume and Issue: 146(5), P. 2029 - 2044

Published: Feb. 15, 2023

Abstract Staging the severity of Alzheimer’s disease pathology using biomarkers is useful for therapeutic trials and clinical prognosis. Disease staging with amyloid tau PET has face validity; however, this would be more practical plasma biomarkers. Our objectives were, first, to examine approaches and, second, prediction stages Participants (n = 1136) were enrolled in either Mayo Clinic Study Aging or Research Center; had a concurrent PET, blood draw; met criteria cognitively unimpaired 864), mild cognitive impairment 148) syndrome dementia 124). The latter two groups combined into impaired group 272). We used multinomial regression models estimate discrimination [concordance (C) statistics] among three (low, intermediate, high), four (Braak 0, 1–2, 3–4, 5–6) stage (none/low versus intermediate/high severity) as predictors separately within individuals. Plasma analytes, p-tau181, Aβ1–42 Aβ1–40 (analysed Aβ42/Aβ40 ratio), glial fibrillary acidic protein neurofilament light chain measured on HD-X Simoa Quanterix platform. p-tau217 was also subset 355) participants Lilly Meso Scale Discovery assay. Models all analytes along risk factors (age, sex APOE) most often provided best (C 0.78–0.82). p-tau181 similar 0.72–0.85 C 0.73–0.86). Discriminating proxy from none/low neuropathological change excellent but not better than only 0.88 0.87 0.91 0.90 impaired). outperformed assay discriminating high intermediate 0.85 0.74) did improve over model 0.83). can discriminate between surrogate accuracy acceptable range. Combinations are single many predictions exception that alone usually performed equivalently combinations discrimination.

Language: Английский

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Revolutionizing the Early Detection of Alzheimer’s Disease through Non-Invasive Biomarkers: The Role of Artificial Intelligence and Deep Learning

Sensors, Journal Year: 2023, Volume and Issue: 23(9), P. 4184 - 4184

Published: April 22, 2023

Alzheimer's disease (AD) is now classified as a silent pandemic due to concerning current statistics and future predictions. Despite this, no effective treatment or accurate diagnosis currently exists. The negative impacts of invasive techniques the failure clinical trials have prompted shift in research towards non-invasive treatments. In light there growing need for early detection AD through approaches. abundance data generated by such blood component monitoring, imaging, wearable sensors, bio-sensors not only offers platform more reliable bio-marker developments but also significantly reduces patient pain, psychological impact, risk complications, cost. Nevertheless, are challenges computational analysis large quantities generated, which can provide crucial information AD. Hence, integration artificial intelligence deep learning critical addressing these challenges. This work attempts examine some facts situation approaches leveraging potential tools utilizing vast amount order revolutionize according principles new medicine era.

Language: Английский

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The potential of blood neurofilament light as a marker of neurodegeneration for Alzheimer's disease

Brain, Journal Year: 2023, Volume and Issue: 147(1), P. 12 - 25

Published: Aug. 2, 2023

Over the past several years, there has been a surge in blood biomarker studies examining value of plasma or serum neurofilament light (NfL) as neurodegeneration for Alzheimer's disease. However, have limited efforts to combine existing findings assess utility NfL In addition, we still need better insight into specific aspects that are reflected by elevated concentration NfL. this review, survey literature on cross-sectional and longitudinal relationships between blood-based levels other, neuroimaging-based, indices individuals continuum. Then, based classification established FDA-NIH Biomarker Working group, determine marker monitoring disease status (i.e. biomarker) predicting severity older adults with without cognitive decline prognostic risk/susceptibility biomarker). The current suggest exhibits great promise because an increased level appears reflect atrophy, hypometabolism white matter integrity, particularly brain regions typically affected Longitudinal evidence indicates can be useful not only progression patients but also susceptibility/risk likelihood abnormal alterations structure function cognitively unimpaired higher risk developing (e.g. those amyloid-β). There limitations research, discussed review. Nevertheless, extant strongly suggests serve valuable susceptibility disease-related clinical settings, well research settings.

Language: Английский

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Glymphatic system dysfunction predicts amyloid deposition, neurodegeneration, and clinical progression in Alzheimer's disease

Alzheimer s & Dementia, Journal Year: 2024, Volume and Issue: 20(5), P. 3251 - 3269

Published: March 19, 2024

Abstract INTRODUCTION Although glymphatic function is involved in Alzheimer's disease (AD), its potential for predicting the pathological and clinical progression of AD sequential association with core biomarkers poorly understood. METHODS Whole‐brain activity was measured by diffusion tensor image analysis along perivascular space (DTI‐ALPS) participants dementia ( n = 47), mild cognitive impairment (MCI; 137), normal controls 235) from Disease Neuroimaging Initiative. RESULTS ALPS index significantly lower than MCI or controls. Lower associated faster changes amyloid positron emission tomography (PET) burden signature region interest volume, higher risk amyloid‐positive transition progression, rates amyloid‐ neurodegeneration‐related decline. Furthermore, associations decline were fully mediated PET brain atrophy. DISCUSSION Glymphatic failure may precede pathology, predicts deposition, neurodegeneration, AD. Highlights The (ALPS) reduced patients (AD) dementia, prodromal AD, preclinical predicted accelerated beta (Aβ) Aβ‐positive transition. decrease occurs before cerebrospinal fluid Aβ42 reaches positive threshold. atrophy, Aβ atrophy link

Language: Английский

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

Protein & Cell, Journal Year: 2024, Volume and Issue: unknown

Published: May 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.

Language: Английский

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Blood Biomarkers of Alzheimer’s Disease and Cognition: A Literature Review

Biomolecules, Journal Year: 2024, Volume and Issue: 14(1), P. 93 - 93

Published: Jan. 11, 2024

Recent advances in blood-based biomarkers of Alzheimer’s Disease (AD) show great promise for clinical applications, offering a less invasive alternative to current cerebrospinal fluid (CSF) measures. However, the relationships between these and specific cognitive functions, as well their utility predicting longitudinal decline, are not yet fully understood. This descriptive review surveys literature from 2018 2023, focusing on associations amyloid-β (Aβ), Total Tau (t-Tau), Phosphorylated (p-Tau), Neurofilament Light (NfL), Glial Fibrillary Acidic Protein (GFAP) with The reviewed studies heterogeneous, varying design population (cognitively unimpaired, cognitively impaired, or mixed populations), results that sometimes conflicting. Generally, cognition positively correlates Aβ levels, especially when evaluated through Aβ42/Aβ40 ratio. In contrast, t-Tau, p-Tau, Nfl, GFAP levels typically negative correlation performance. While p-Tau measures generally exhibit stronger functions compared other biomarkers, no single blood marker has emerged being predominantly linked domain. These findings contribute our understanding complex relationship performance underscore potential assessments cognition.

Language: 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, Journal Year: 2025, Volume and Issue: 17(1)

Published: Jan. 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.

Language: Английский

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Association of rapid eye movement sleep latency with multimodal biomarkers of Alzheimer's disease

Alzheimer s & Dementia, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 27, 2025

Abstract INTRODUCTION Sleep disturbances are associated with Alzheimer's disease (AD) and related dementias (ADRD), but the relationship between sleep architecture, particularly rapid eye movement (REM) sleep, AD/ADRD biomarkers remains unclear. METHODS We enrolled 128 adults (64 disease, 41 mild cognitive impairment [MCI], 23 normal cognition [NC]), mean age 70.8 ± 9.6 years, 56.9% female, from a tertiary hospital in China. Participants underwent overnight polysomnography (PSG), amyloid β (Aβ) positron emission tomography (PET), plasma biomarker analysis: phosphorylated tau at threonine 181 (p‐tau181), neurofilament light (NfL), brain‐derived neurotrophic factor (BDNF). RESULTS After adjusting for demographics, apolipoprotein E ( APOE ) ε4 status, cognition, comorbidities, highest tertile of REM latency was higher Aβ burden = 0.08, 95% confidence interval [CI]: 0.03 to 0.13, p 0.002), elevated p‐tau181 0.19, CI: 0.02 reduced BDNF levels ‐0.47, –0.68 –0.13, 0.013), compared lowest tertile. DISCUSSION Prolonged may serve as novel marker or risk pathogenesis. Highlights Rapid (REML) be potential (AD/ADRD) REML beta burden, tau‐181 lower (BDNF) levels. Intervention trial is needed determine if targeting can modify risk. Slow‐wave not biomarkers.

Language: Английский

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