Tau biomarkers in Alzheimer's disease: towards implementation in clinical practice and trials

The Lancet Neurology, Journal Year: 2022, Volume and Issue: 21(8), P. 726 - 734

Published: May 25, 2022

Language: Английский

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Head-to-head comparison of 10 plasma phospho-tau assays in prodromal Alzheimer’s disease

Brain, Journal Year: 2022, Volume and Issue: 146(4), P. 1592 - 1601

Published: Sept. 10, 2022

Plasma phospho-tau (p-tau) species have emerged as the most promising blood-based biomarkers of Alzheimer's disease. Here, we performed a head-to-head comparison p-tau181, p-tau217 and p-tau231 measured using 10 assays to detect abnormal brain amyloid-β (Aβ) status predict future progression dementia. The study included 135 patients with baseline diagnosis mild cognitive impairment (mean age 72.4 years; 60.7% women) who were followed for an average 4.9 years. Seventy-one participants had Aβ-status (i.e. CSF Aβ42/40) at baseline; 45 these Aβ-positive progressed dementia during follow-up. P-tau concentrations determined in plasma CSF. P-tau217 p-tau181 both immunoassays developed by Lilly Research Laboratories (Lilly) mass spectrometry Washington University (WashU). was also analysed Simoa immunoassay Janssen Development (Janss). P-tau181 from ADxNeurosciences (ADx), Lumipulse Fujirebio (Fuji) Splex Mesoscale Discovery (Splex). Both quantified Gothenburg (UGOT). We found that spectrometry-based (p-tau217WashU) exhibited significantly better performance than all other p-tau when detecting Aβ [area under curve (AUC) = 0.947; Pdiff < 0.015] or (AUC 0.932; 0.027). Among immunoassays, p-tau217Lilly highest AUCs (0.886-0.889), which not different p-tau217Janss, p-tau181ADx p-tau181WashU (AUCrange 0.835-0.872; > 0.09), but higher compared AUC p-tau231UGOT, p-tau181Lilly, p-tau181UGOT, p-tau181Fuji p-tau181Splex 0.642-0.813; ≤ 0.029). Correlations between values strongest p-tau217WashU (R 0.891) 0.755; 0.003 versus p-tau217WashU) weak moderate rest (Rrange 0.320-0.669). In conclusion, our findings suggest among tested assays, measures perform best identifying those will subsequently progress Several (p-tau217Lilly, p-tau181WashU) showed relatively high consistent accuracy across outcomes. results further indicate performing metrics rival gold standards Aβ-PET If validated, significant impacts diagnosis, screening treatment future.

Language: Английский

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Hypothesis: Tau pathology is an initiating factor in sporadic Alzheimer's disease

Alzheimer s & Dementia, Journal Year: 2020, Volume and Issue: 17(1), P. 115 - 124

Published: Oct. 19, 2020

Abstract The etiology of the common, sporadic form Alzheimer's disease (sAD) is unknown. We hypothesize that tau pathology within select projection neurons with susceptible microenvironments can initiate sAD. This postulate rests on extensive data demonstrating in human brains appears about a decade before formation Aβ plaques (Aβps), especially targeting glutamate association cortex. Data from aging rhesus monkeys show abnormal phosphorylation vulnerable neurons, associated calcium dysregulation. Abnormally phosphorylated (pTau) microtubules traps APP‐containing endosomes, which increase production. As oligomers tau, this would drive vicious cycles leading to sAD over long lifespan, genetic and environmental factors may accelerate pathological events. hypothesis could be testable aged monkey cortex naturally expresses characteristics capable promoting sustaining

Language: Английский

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Associations of Plasma Phospho-Tau217 Levels With Tau Positron Emission Tomography in Early Alzheimer Disease

JAMA Neurology, Journal Year: 2020, Volume and Issue: 78(2), P. 149 - 149

Published: Nov. 9, 2020

There is an urgent need for inexpensive and minimally invasive blood biomarkers Alzheimer disease (AD) that could be used to detect early changes.To assess how in the course of AD plasma levels tau phosphorylated at threonine 217 (P-tau217) start change compared with established cerebrospinal fluid (CSF) positron emission tomography (PET) pathology.This cohort study included cognitively healthy control individuals (n = 225) participants subjective cognitive decline 89) or mild impairment 176) from BioFINDER-2 study. Participants were enrolled 2 different hospitals Sweden January 2017 October 2019. All underwent P-tau217 assessments tau- amyloid-β (Aβ)-PET imaging. A subcohort 111 had 3 tau-PET scans.Changes preclinical prodromal changes CSF PET measures.Of 490 participants, 251 women (51.2%) mean (SD) age was 65.9 (13.1) years. Plasma increased unimpaired abnormal Aβ-PET but normal entorhinal cortex (Aβ-PET+/ tau-PET- group vs Aβ-PET-/ group: median, 2.2 pg/mL [interquartile range (IQR), 1.5-2.9 pg/mL] 0.7 [IQR, 0.3-1.4 pg/mL]). Most who discordant positive negative (P-tau217+/tau-PET-: 36 [94.7%]; P-tau217-/tau-PET+: [5.3%]). Event-based modeling cross-sectional data predicted those impairment, both would before signal cortex, followed by more widespread cortical changes. When testing association global Aβ load nonlinear spline models, lower values measures. Among baseline tau-PET, rates longitudinal increase higher (median standardized uptake value ratio, 0.029 -0.006 0.041] -0.001 -0.021 0.020]; Mann-Whitney U, P .02).In this study, during stages when insoluble aggregates not yet detectable tau-PET. may hold promise as a biomarker brain pathology.

Language: Английский

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The China Alzheimer Report 2022

General Psychiatry, Journal Year: 2022, Volume and Issue: 35(1), P. e100751 - e100751

Published: Feb. 1, 2022

China's population has rapidly aged over the recent decades of social and economic development as neurodegenerative disorders have proliferated, especially Alzheimer's disease (AD) related dementias (ADRD). AD's incidence rate, morbidity, mortality steadily increased to make it presently fifth leading cause death among urban rural residents in China magnify resulting financial burdens on individuals, families society. The 'Healthy Action' plan 2019-2030 promotes transition from treatment health maintenance for this expanding with ADRD. This report describes epidemiological trends, evaluates burden disease, outlines current clinical diagnosis status delineates existing available public resources. More specifically, examines impact ADRD, including prevalence, mortality, costs, usage care, overall effect caregivers In addition, special presents technical guidance supports prevention AD, provides expertise guide relevant governmental healthcare policy suggests an information platform international exchange cooperation.

Language: Английский

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Longitudinal plasma p-tau217 is increased in early stages of Alzheimer’s disease

Brain, Journal Year: 2020, Volume and Issue: 143(11), P. 3234 - 3241

Published: Oct. 15, 2020

Plasma levels of tau phosphorylated at threonine-217 (p-tau217) is a candidate tool to monitor Alzheimer's disease. We studied 150 cognitively unimpaired participants and 100 patients with mild cognitive impairment in the Swedish BioFINDER study. P-tau217 was measured repeatedly for up 6 years (median three samples per person, median time from first last sample, 4.3 years). Preclinical (amyloid-β-positive unimpaired, n = 62) prodromal impairment, 49) disease had accelerated p-tau217 compared amyloid-β-negative (β 0.56, P < 0.001, using linear mixed effects models) 0.67, 0.001), respectively. Mild who later converted dementia (n 40) other 0.79, 0.001). did not change participants, or convert dementia. For 80% power, 109 arm were required observe slope reduction amyloid-β-positive (71 impairment). Longitudinal increases correlated longitudinal worsening cognition brain atrophy. In summary, plasma during early can be used progression.

Language: Английский

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Blood biomarkers for Alzheimer’s disease in clinical practice and trials

Nature Aging, Journal Year: 2023, Volume and Issue: 3(5), P. 506 - 519

Published: May 18, 2023

Language: Английский

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Blood‐based biomarkers for Alzheimer's disease

EMBO Molecular Medicine, Journal Year: 2021, Volume and Issue: 14(1)

Published: Dec. 3, 2021

Language: Английский

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Blood phospho-tau in Alzheimer disease: analysis, interpretation, and clinical utility

Nature Reviews Neurology, Journal Year: 2022, Volume and Issue: 18(7), P. 400 - 418

Published: May 18, 2022

Language: Английский

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Neurofilament Proteins as Biomarkers to Monitor Neurological Diseases and the Efficacy of Therapies

Frontiers in Neuroscience, Journal Year: 2021, Volume and Issue: 15

Published: Sept. 27, 2021

Biomarkers of neurodegeneration and neuronal injury have the potential to improve diagnostic accuracy, disease monitoring, prognosis, measure treatment efficacy. Neurofilament proteins (NfPs) are well suited as biomarkers in these contexts because they major neuron-specific components that maintain structural integrity sensitive across a wide range neurologic diseases. Low levels NfPs constantly released from neurons into extracellular space ultimately reach cerebrospinal fluid (CSF) blood under physiological conditions throughout normal brain development, maturation, aging. NfP CSF rise above response independently cause. measured by lumbar puncture about 40-fold more concentrated than healthy individuals. New ultra-sensitive methods now allow minimally invasive measurement low serum or plasma track onset progression neurological disorders nervous system assess responses therapeutic interventions. Any five Nf subunits – neurofilament light chain (NfL), medium (NfM), heavy (NfH), alpha-internexin (INA) peripherin (PRPH) may be altered given neuropathological condition. In familial sporadic Alzheimer’s (AD), NfL early 22 years before clinical AD 10 AD. The determinants elevated degradation fragments magnitude damaged degenerating axons fiber tracks, affected axon caliber sizes rate release at different stages condition directly indirectly affecting central (CNS) and/or peripheral (PNS). rapidly emerging transformative neurology providing novel insights diseases advancing trials. Here we summarize current understanding intracellular physiology, pathophysiology kinetics biofluids review value limitations injury.

Language: Английский

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