Revised criteria for diagnosis and staging of Alzheimer's disease: Alzheimer's Association Workgroup

Alzheimer s & Dementia, Journal Year: 2024, Volume and Issue: 20(8), P. 5143 - 5169

Published: June 27, 2024

Abstract The National Institute on Aging and the Alzheimer's Association convened three separate work groups in 2011 single 2012 2018 to create recommendations for diagnosis characterization of disease (AD). present document updates research framework response several recent developments. Defining diseases biologically, rather than based syndromic presentation, has long been standard many areas medicine (e.g., oncology), is becoming a unifying concept common all neurodegenerative diseases, not just AD. consistent with this principle. Our intent objective criteria staging AD, incorporating advances biomarkers, serve as bridge between clinical care. These are intended provide step‐by‐step practice guidelines workflow or specific treatment protocols, but general principles inform AD that reflect current science. Highlights We define (AD) be biological process begins appearance neuropathologic change (ADNPC) while people asymptomatic. Progression burden leads later progression symptoms. Early‐changing Core 1 biomarkers (amyloid positron emission tomography [PET], approved cerebrospinal fluid accurate plasma [especially phosphorylated tau 217]) map onto either amyloid beta tauopathy pathway; however, these presence ADNPC more generally (i.e., both neuritic plaques tangles). An abnormal biomarker result sufficient establish decision making throughout continuum. Later‐changing 2 (biofluid PET) can prognostic information, when abnormal, will increase confidence contributing integrated scheme described accommodates fact copathologies, cognitive reserve, resistance may modify relationships stages.

Language: Английский

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Blood-based biomarkers for Alzheimer's disease: towards clinical implementation

The Lancet Neurology, Journal Year: 2021, Volume and Issue: 21(1), P. 66 - 77

Published: Nov. 25, 2021

Language: Английский

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Traumatic Brain Injury and Risk of Neurodegenerative Disorder

Biological Psychiatry, Journal Year: 2021, Volume and Issue: 91(5), P. 498 - 507

Published: June 2, 2021

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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“Don’t Phos Over Tau”: recent developments in clinical biomarkers and therapies targeting tau phosphorylation in Alzheimer’s disease and other tauopathies

Molecular Neurodegeneration, Journal Year: 2021, Volume and Issue: 16(1)

Published: June 5, 2021

Phosphorylation is one of the most prevalent post-translational modifications found in aggregated tau isolated from Alzheimer's disease (AD) patient brains. In tauopathies like AD, increased phosphorylation or hyperphosphorylation can contribute to microtubule dysfunction and associated with aggregation. this review, we provide an overview structure functions protein as well physiologic roles phosphorylation. We also extensively survey sites identified brain tissue cerebrospinal fluid AD patients compared age-matched healthy controls, which may serve disease-specific biomarkers. Recently, new assays have been developed measure minute amounts specific forms phosphorylated both plasma, could potentially be useful for aiding clinical diagnosis monitoring progression. Additionally, multiple therapies targeting are various stages trials including kinase inhibitors, phosphatase activators, immunotherapy. With promising early results, that target at slowing aggregation other tauopathies.

Language: Английский

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Plasma Aβ42/40 ratio, p‐tau181, GFAP, and NfL across the Alzheimer's disease continuum: A cross‐sectional and longitudinal study in the AIBL cohort

Alzheimer s & Dementia, Journal Year: 2022, Volume and Issue: 19(4), P. 1117 - 1134

Published: July 21, 2022

Plasma amyloid beta (Aβ)1-42/Aβ1-40 ratio, phosphorylated-tau181 (p-tau181), glial fibrillary acidic protein (GFAP), and neurofilament light (NfL) are putative blood biomarkers for Alzheimer's disease (AD). However, head-to-head cross-sectional longitudinal comparisons of the aforementioned across AD continuum lacking.Plasma Aβ1-42, Aβ1-40, p-tau181, GFAP, NfL were measured utilizing Single Molecule Array (Simoa) platform compared cross-sectionally continuum, wherein Aβ-PET (positron emission tomography)-negative cognitively unimpaired (CU Aβ-, n = 81) mild cognitive impairment (MCI 26) participants with Aβ-PET-positive Aβ+, 39; MCI 33; 46) from Australian Imaging, Biomarker & Lifestyle Flagship Study Ageing (AIBL) cohort. Longitudinal plasma biomarker changes also assessed in (n 27) 29) CU 120) participants. In addition, associations between baseline levels prospective decline load over a 7 to 10-year duration.Lower Aβ1-42/Aβ1-40 ratio elevated p-tau181 GFAP observed whereas was Aβ+ Aβ- Aβ-. Among biomarkers, models without risk factors (age, sex, apolipoprotein E (APOE) ε4 carrier status), performed equivalent or better than other predicting brain Aβ-/+ status continuum. factors, panel Aβ1-42/Aβ1-40, any alone Longitudinally, altered CU, CU. lower higher associated increased prospectively.These findings suggest that longitudinally, along prospectively load. although an may have superior predictive capability continuum.Area under curve (AUC) ≥ AUC Aβ42/40, PET (Aβ-/+). Aβ42/40+p-tau181+GFAP Aβ42/40/p-tau181/GFAP/NfL Aβ-/+. versus decline. Aβ prospectively.

Language: Английский

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Comparison of serum neurodegenerative biomarkers among hospitalized COVID‐19 patients versus non‐COVID subjects with normal cognition, mild cognitive impairment, or Alzheimer's dementia

Alzheimer s & Dementia, Journal Year: 2022, Volume and Issue: 18(5), P. 899 - 910

Published: Jan. 13, 2022

Abstract Introduction Neurological complications among hospitalized COVID‐19 patients may be associated with elevated neurodegenerative biomarkers. Methods Among without a history of dementia (N = 251), we compared serum total tau (t‐tau), phosphorylated tau‐181 (p‐tau181), glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), ubiquitin carboxy‐terminal hydrolase L1 (UCHL1), and amyloid beta (Aβ40,42) between or encephalopathy, in‐hospital death versus survival, discharge home other dispositions. patient biomarker levels were also to non‐COVID cognitively normal, mild cognitive impairment (MCI), Alzheimer's disease (AD) controls 161). Results Admission t‐tau, p‐tau181, GFAP, NfL significantly in encephalopathy those who died in‐hospital, while lower discharged home. These markers correlated severity COVID illness. NfL, UCHL1 higher than MCI AD. Discussion Neurodegenerative biomarkers observed AD worse outcomes patients.

Language: Английский

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Confounding factors of Alzheimer's disease plasma biomarkers and their impact on clinical performance

Alzheimer s & Dementia, Journal Year: 2022, Volume and Issue: 19(4), P. 1403 - 1414

Published: Sept. 24, 2022

Abstract Introduction Plasma biomarkers will likely revolutionize the diagnostic work‐up of Alzheimer's disease (AD) globally. Before widespread use, we need to determine if confounding factors affect levels these biomarkers, and their clinical utility. Methods Participants with plasma CSF creatinine, body mass index (BMI), medical history data were included (BioFINDER‐1: n = 748, BioFINDER‐2: 421). We measured beta‐amyloid (Aβ42, Aβ40), phosphorylated tau (p‐tau217, p‐tau181), neurofilament light (NfL), glial fibrillary acidic protein (GFAP). Results In both cohorts, creatinine BMI main associated NfL, GFAP, a lesser extent p‐tau. However, adjustment for had only minor effects in models predicting either corresponding or subsequent development dementia. Discussion Creatinine are related certain levels, but they do not have clinically relevant vast majority individuals. Highlights (BMI) biomarker levels. Adjusting has influence on plasma‐cerebrospinal fluid (CSF) associations. prediction dementia using biomarkers.

Language: Английский

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