Machine learning prediction of tau‐PET in Alzheimer's disease using plasma, MRI, and clinical data DOI Creative Commons
Linda Karlsson, Jacob W. Vogel, Ida Arvidsson

и другие.

Alzheimer s & Dementia, Год журнала: 2025, Номер 21(2)

Опубликована: Фев. 1, 2025

Abstract INTRODUCTION Tau positron emission tomography (PET) is a reliable neuroimaging technique for assessing regional load of tau pathology in the brain, but its routine clinical use limited by cost and accessibility barriers. METHODS We thoroughly investigated ability various machine learning models to predict clinically useful tau‐PET composites (load laterality index) from low‐cost non‐invasive features, example, variables, plasma biomarkers, structural magnetic resonance imaging (MRI). RESULTS Models including biomarkers yielded most accurate predictions burden (best model: R ‐squared = 0.66–0.69), with especially high contribution phosphorylated tau‐217 (p‐tau217). MRI variables were best predictors asymmetric between two hemispheres 0.28–0.42). The showed generalizability external test cohorts data collected at multiple sites. Through proof‐of‐concept two‐step classification workflow, we also demonstrated possible model translations setting. DISCUSSION This study highlights promising limiting aspects using scalable cost‐effective findings relevant settings future research. Highlights Accessible potential estimating tangle distribution. Plasma (p‐tau217) (MRI) different (positron tomography) composites. Machine across AD cohorts.

Язык: Английский

Revised criteria for diagnosis and staging of Alzheimer's disease: Alzheimer's Association Workgroup DOI Creative Commons
Clifford R. Jack,

J. Scott Andrews,

Thomas G. Beach

и другие.

Alzheimer s & Dementia, Год журнала: 2024, Номер 20(8), С. 5143 - 5169

Опубликована: Июнь 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.

Язык: Английский

Процитировано

598
Biomarker-based staging of Alzheimer disease: rationale and clinical applications DOI
Joseph Therriault, Suzanne E. Schindler, Gemma Salvadó

и другие.

Nature Reviews Neurology, Год журнала: 2024, Номер 20(4), С. 232 - 244

Опубликована: Март 1, 2024

Язык: Английский

Процитировано

65
Diagnostic performance of plasma pTau217, pTau181, Aβ1-42 and Aβ1-40 in the LUMIPULSE automated platform for the detection of Alzheimer disease DOI Creative Commons
Javier Arranz, Nuole Zhu, Sara Rubio‐Guerra

и другие.

Alzheimer s Research & Therapy, Год журнала: 2024, Номер 16(1)

Опубликована: Июнь 26, 2024

Abstract Background Recently developed blood markers for Alzheimer's disease (AD) detection have high accuracy but usually require ultra-sensitive analytic tools not commonly available in clinical laboratories, and their performance practice is unknown. Methods We analyzed plasma samples from 290 consecutive participants that underwent lumbar puncture routine a specialized memory clinic (66 cognitively unimpaired, 130 with mild cognitive impairment, 94 dementia). Participants were classified as amyloid positive (A +) or negative (A-) according to CSF Aβ 1–42 /Aβ 1–40 ratio. Plasma pTau 217 , 181 measured the fully-automated LUMIPULSE platform. used linear regression compare biomarkers concentrations between A + A- groups, evaluated Spearman’s correlation performed ROC analyses assess diagnostic detect brain amyloidosis determined by concordance of amyloidosis. Results concentration higher than while ratio was lower compared A-. showed moderate (Rho = 0.66 0.69, respectively). The areas under curve discriminate 0.94 (95% CI 0.92–0.97) 0.88 0.84–0.92) both . Chronic kidney (CKD) related increased biomarker concentrations, ratios less affected. had highest fold change (× 3.2) predictive capability discriminating A-, having 4–7% misclassification rate. global using two-threshold approach robust symptomatic exceeding 90%. Conclusion evaluation on an automated platform exhibited AD pathophysiology, excellent identify sample representing unit.

Язык: Английский

Процитировано

42
Synergistic association of Aβ and tau pathology with cortical neurophysiology and cognitive decline in asymptomatic older adults DOI Creative Commons
Jonathan Gallego-Rudolf, Alex I. Wiesman, Alexa Pichet Binette

и другие.

Nature Neuroscience, Год журнала: 2024, Номер unknown

Опубликована: Сен. 18, 2024

Язык: Английский

Процитировано

24
Comparison of plasma biomarkers and amyloid PET for predicting memory decline in cognitively unimpaired individuals DOI Creative Commons
Clifford R. Jack,

Heather J. Wiste,

Alicia Algeciras‐Schimnich

и другие.

Alzheimer s & Dementia, Год журнала: 2024, Номер 20(3), С. 2143 - 2154

Опубликована: Янв. 24, 2024

Abstract BACKGROUND We compared the ability of several plasma biomarkers versus amyloid positron emission tomography (PET) to predict rates memory decline among cognitively unimpaired individuals. METHODS studied 645 Mayo Clinic Study Aging participants. Predictor variables were age, sex, education, apolipoprotein E ( APOE ) ε 4 genotype, PET, and beta (Aβ)42/40, phosphorylated tau (p‐tau)181, neurofilament light (NfL), glial fibrillary acidic protein (GFAP), p‐tau217. The outcome was a change in composite measure. RESULTS All biomarkers, except NfL, associated with mean models individual biomarkers. However, PET p‐tau217, along key independently combining all predictors. Confidence intervals narrow for estimates population prediction, but person‐level prediction wide. DISCUSSION Plasma p‐tau217 provide useful information about predicting future cognitive individuals at level, not person level.

Язык: Английский

Процитировано

19
Differential roles of Alzheimer's disease plasma biomarkers in stepwise biomarker‐guided diagnostics DOI Creative Commons
Hyemin Jang, Daeun Shin, Heejin Yoo

и другие.

Alzheimer s & Dementia, Год журнала: 2025, Номер unknown

Опубликована: Фев. 5, 2025

Abstract INTRODUCTION This study aimed to investigate the differential roles of various plasma biomarkers in a stepwise diagnostic strategy for Alzheimer's disease (AD). METHODS A total 2984 participants, including 666 cognitively unimpaired (CU), 2032 with clinical syndrome (ACS), and 286 non‐ACS individuals, were recruited. Plasma amyloid beta (Aβ) 42/40, four phosphorylated tau (p‐tau) epitopes, glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL) levels measured using immunoassays. RESULTS NfL demonstrated fair excellent accuracy differentiating from CU groups (area under curve [AUC], 0.79 0.94). p‐tau217 had highest identifying Aβ (AUC 0.94) positron emission tomography status 0.91). In ACS group, was strongest predictor cognitive decline (p < .001). DISCUSSION may serve as useful screening tool, while is particularly valuable confirming AD pathology prognosis. Highlights could screen impairment. reliably detects pathology, regardless diagnosis. GFAP predict prognosis ACS. Each biomarker plays distinct role diagnostics.

Язык: Английский

Процитировано

3
Challenges in the practical implementation of blood biomarkers for Alzheimer’s disease DOI Creative Commons
Michael Schöll, Inge M.W. Verberk, Marta del Campo

и другие.

The Lancet Healthy Longevity, Год журнала: 2024, Номер 5(10), С. 100630 - 100630

Опубликована: Окт. 1, 2024

Язык: Английский

Процитировано

17
Comparison of immunoassay- with mass spectrometry-derived p-tau quantification for the detection of Alzheimer’s disease pathology DOI Creative Commons
Joseph Therriault, Marcel S. Woo, Gemma Salvadó

и другие.

Molecular Neurodegeneration, Год журнала: 2024, Номер 19(1)

Опубликована: Янв. 7, 2024

Abstract Background Antibody-based immunoassays have enabled quantification of very low concentrations phosphorylated tau (p-tau) protein forms in cerebrospinal fluid (CSF), aiding the diagnosis AD. Mass spectrometry enables absolute multiple p-tau variants within a single run. The goal this study was to compare performance mass assessments 181 , 217 and 231 with established immunoassay techniques. Methods We measured CSF from 173 participants TRIAD cohort 394 BioFINDER-2 using both methods. All subjects were clinically evaluated by dementia specialists had amyloid-PET tau-PET assessments. Bland–Altman analyses agreement between . P-tau associations uptake also compared. Receiver Operating Characteristic (ROC) compared identify positivity. Results highly comparable terms diagnostic performance, between-group effect sizes PET biomarkers. In contrast, antibody-free lower immunoassays. Conclusions Our results suggest that while similar overall, immunoassay-based biomarkers are slightly superior spectrometry-based Future work is needed determine whether potential evaluate run offsets quantification.

Язык: Английский

Процитировано

16
The impact of kidney function on plasma neurofilament light and phospho-tau 181 in a community-based cohort: the Shanghai Aging Study DOI Creative Commons
Jie Wu, Zhenxu Xiao, Mengjing Wang

и другие.

Alzheimer s Research & Therapy, Год журнала: 2024, Номер 16(1)

Опубликована: Фев. 12, 2024

Abstract Background The blood-based biomarkers are approaching the clinical practice of Alzheimer’s disease (AD). Chronic kidney (CKD) has a potential confounding effect on peripheral protein levels. It is essential to characterize impact renal function AD markers. Methods Plasma phospho-tau181 (P-tau181), and neurofilament light (NfL) were assayed via Simoa HD-X platform in 1189 dementia-free participants from Shanghai Aging Study (SAS). estimated glomerular filter rate (eGFR) was calculated. association between blood NfL, P-tau181 analyzed. An analysis interactions various demographic comorbid factors eGFR conducted. Results levels negatively associated with plasma concentrations NfL ( B = − 0.19, 95% CI 0.224 0.156, P < 0.001; 0.009, 0.013 -0.005, 0.001, respectively). After adjusting for characteristics diseases, remained significantly correlated 0.010, 0.133 0.068, 0.001), but not 0.003, 0.007 0.194). A significant interaction age found 0.001). In ≥ 70 years 60 ml/min/1.73 m 2 , correlation remarkable 0.790, 1.026 0,554, Conclusions Considering crucial when interpreting general aging population.

Язык: Английский

Процитировано

16
New precision medicine avenues to the prevention of Alzheimer’s disease from insights into the structure and function of γ-secretases DOI Creative Commons
Bart De Strooper, Eric Karran

The EMBO Journal, Год журнала: 2024, Номер 43(6), С. 887 - 903

Опубликована: Фев. 23, 2024

Abstract Two phase-III clinical trials with anti-amyloid peptide antibodies have met their primary goal, i.e. slowing of Alzheimer’s disease (AD) progression. However, antibody therapy may not be the optimal therapeutic modality for AD prevention, as we will discuss in context earlier small molecules described “γ-secretase modulators” (GSM). We review here structure, function, and pathobiology γ-secretases, a focus on how mutations presenilin genes result early-onset AD. Significant progress has been made generating compounds that act manner opposite to pathogenic mutations: they stabilize proteinase-substrate complex, thereby increasing processivity substrate cleavage altering size spectrum Aβ peptides produced. propose term allosteric stabilizers” (GSAS) distinguish these from rather heterogenous class GSM. The GSAS represent, theory, precision medicine approach prevention amyloid deposition, specifically target discrete aspect complex cell biological signalling mechanism initiates pathological processes leading disease.

Язык: Английский

Процитировано

14