Artificial intelligence for biomarker discovery in Alzheimer's disease and dementia

Alzheimer s & Dementia, Journal Year: 2023, Volume and Issue: 19(12), P. 5860 - 5871

Published: Aug. 31, 2023

Abstract With the increase in large multimodal cohorts and high‐throughput technologies, potential for discovering novel biomarkers is no longer limited by data set size. Artificial intelligence (AI) machine learning approaches have been developed to detect interactions complex sets. We discuss exemplar uses evaluate current applications limitations of AI discover biomarkers. Remaining challenges include a lack diversity sets available, sheer complexity investigating interactions, invasiveness cost some biomarkers, poor reporting studies. Overcoming these will involve collecting from underrepresented populations, developing more powerful approaches, validating use noninvasive adhering guidelines. By harnessing rich through international collaborative innovation, we are well positioned identify clinically useful that accurate, generalizable, unbiased, acceptable clinical practice. Highlights may accelerate dementia biomarker discovery. suitability due size bias cohort selection. Multimodal data, diverse sets, improved real‐world validation, interdisciplinary collaboration required.

Language: Английский

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A novel ultrasensitive assay for plasma p‐tau217: Performance in individuals with subjective cognitive decline and early Alzheimer's disease

Alzheimer s & Dementia, Journal Year: 2023, Volume and Issue: 20(2), P. 1239 - 1249

Published: Nov. 17, 2023

Abstract INTRODUCTION Detection of Alzheimer's disease (AD) pathophysiology among individuals with mild cognitive changes and those experiencing subjective decline (SCD) remains challenging. Plasma phosphorylated tau 217 (p‐tau217) is one the most promising emerging biomarkers for AD. However, accessible methods are limited. METHODS We employed a novel p‐tau217 immunoassay (University Gothenburg [UGOT] p‐tau217) in four independent cohorts ( n = 308) including cerebrospinal fluid (CSF) biomarker‐classified cohort (Discovery), two consisting mostly cognitively unimpaired (CU) impaired (MCI) participants (MYHAT Pittsburgh), population‐based SCD (Barcelonaβeta Brain Research Center's At‐Risk Cohort [β‐AARC]). RESULTS UGOT showed high accuracy (area under curve [AUC] 0.80–0.91) identifying amyloid beta (Aβ) pathology, determined either by Aβ positron emission tomography or CSF Aβ42/40 ratio. In SCD, positive ratio (AUC 0.91). DISCUSSION can be an easily efficient way to screen monitor patients suspected AD pathophysiology, even early stages continuum.

Language: Английский

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Head-to-head study of diagnostic accuracy of plasma and cerebrospinal fluid p-tau217 versus p-tau181 and p-tau231 in a memory clinic cohort

Journal of Neurology, Journal Year: 2024, Volume and Issue: 271(4), P. 2053 - 2066

Published: Jan. 9, 2024

Abstract Background and objective Phosphorylated tau ( p -tau) 217 has recently received attention because it seems more reliable than other -tau variants for identifying Alzheimer’s disease (AD) pathology. Thus, we aimed to compare the diagnostic accuracy of plasma CSF -tau217 with -tau181 -tau231 in a memory clinic cohort. Methods The study included 114 participants (CU = 33; MCI 67; Dementia 14). were correlated versus continuous measures amyloid (A) (T)-PET. phospho-epitopes assessed through: (i) effect sizes δ ) between A ± T groups; (ii) receiver operating characteristic (ROC) analyses A-PET T-PET. Results correlations both T-PET r range 0.64–0.83) stronger those 0.44–0.79) 0.46–0.76). Plasma showed significantly higher differences biomarker groups : 0.55–0.96; 0.51–0.67; 0.53–0.71); ROC curves identify positivity (AUC average 0.96; 0.76; 0.79). On hand, 0.95) did not reveal significant AUC 0.88) 0.89). Discussion demonstrated better performance identification AD pathology clinical phenotypes comparison Furthermore, had comparable CSF. Our findings suggest potential diagnosis screening AD, which could allow decreased use invasive biomarkers future.

Language: Английский

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Plasma p-tau212 antemortem diagnostic performance and prediction of autopsy verification of Alzheimer’s disease neuropathology

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: March 23, 2024

Abstract Blood phosphorylated tau (p-tau) biomarkers, including p-tau217, show high associations with Alzheimer’s disease (AD) neuropathologic change and clinical stage. Certain plasma p-tau217 assays recognize forms additionally at threonine-212, but the contribution of p-tau212 alone to AD is unknown. We developed a blood-based immunoassay that specific without cross-reactivity p-tau217. Here, we examined diagnostic utility p-tau212. In five cohorts ( n = 388 participants), showed performances for diagnosis detection both amyloid pathology, autopsy as well in memory clinic populations. The accuracy fold changes were similar those higher than p-tau181 p-tau231. Immunofluorescent staining brain tissue slices prominent reactivity neurofibrillary tangles co-localized p-tau202/205. These findings support peripherally accessible biomarker pathophysiology.

Language: Английский

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Plasma brain-derived tau is an amyloid-associated neurodegeneration biomarker in Alzheimer’s disease

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: April 4, 2024

Abstract Staging amyloid-beta (Aβ) pathophysiology according to the intensity of neurodegeneration could identify individuals at risk for cognitive decline in Alzheimer’s disease (AD). In blood, phosphorylated tau (p-tau) associates with Aβ but an AD-type biomarker has been lacking. this multicenter study ( n = 1076), we show that brain-derived (BD-tau) blood increases concomitant (“A”) and (“N”) abnormalities (determined using cerebrospinal fluid biomarkers); We used blood-based A/N biomarkers profile participants study; p-tau+/BD-tau+ profiles had fastest atrophy rates, irrespective baseline status. Furthermore, BD-tau showed no or much weaker correlations age, renal function, other comorbidities/risk factors self-identified race/ethnicity, compared biomarkers. Here is a identifying Aβ-positive short-term atrophy, implications clinical trials implementation anti-Aβ therapies.

Language: Английский

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The Bio‐Hermes Study: Biomarker database developed to investigate blood‐based and digital biomarkers in community‐based, diverse populations clinically screened for Alzheimer's disease

Alzheimer s & Dementia, Journal Year: 2024, Volume and Issue: 20(4), P. 2752 - 2765

Published: Feb. 28, 2024

Abstract INTRODUCTION Alzheimer's disease (AD) trial participants are often screened for eligibility by brain amyloid positron emission tomography/cerebrospinal fluid (PET/CSF), which is inefficient as many not positive. Use of blood‐based biomarkers may reduce screen failures. METHODS We recruited 755 non‐Hispanic White, 115 Hispanic, 112 Black, and 19 other minority across groups cognitively normal ( n = 417), mild cognitive impairment 312), or AD 272) participants. Plasma beta (Aβ)40, Aβ42, Aβ42/Aβ40, total tau, phosphorylated tau (p‐tau)181, p‐tau217 were measured; PET/CSF 956) determined positivity. Clinical, blood biomarker, ethnicity/race differences associated with status evaluated. RESULTS Greater impairment, older age, carrying an apolipoprotein E (apoE) ε4 allele greater burden. Areas under the receiver operating characteristic curve plasma p‐tau181, positivity ≥ 0.7117 all ethnoracial (p‐tau217, ≥0.8128). Age apoE adjustments imputation biomarker values outside limit quantitation provided small improvement in predictive power. DISCUSSION Blood‐based highly results diverse populations enrolled at clinical sites. Highlights Amyloid (Aβ)42/Aβ40, p‐tau 217 predicted P‐tau was strongest predictor Biomarkers from ethnic, racial, cohorts Community‐based have similar levels populations. A prescreen process assays number

Language: Английский

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Clinical evaluation of a novel plasma pTau217 electrochemiluminescence immunoassay in Alzheimer’s disease

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Jan. 5, 2024

Abstract A growing literature suggests that plasma levels of tau phosphorylated at amino acid 217 (pTau217) performs similarly to cerebrospinal fluid (CSF) biomarkers and PET imaging detect amyloid pathology provide diagnostic prognostic information in Alzheimer’s disease (AD), but a significant limiting factor thus far has been lack widely available immunoassays. We evaluated novel pTau217 S-PLEX® assay developed by Meso Scale Discovery (MSD; Rockville, MD) from 131 individuals with AD confirmed CSF controls. Technical performance the was excellent an LLOQ 1.84 pg/mL intra/interplate CVs 5.5% (0.3–15.0%) 5.7% (range 0.3–13.4%), respectively. The differentiated controls AUC 0.98 (95% CI 0.96–1.0) were 3.9-fold higher AD. This significantly better than what observed for pTau181, performed parallel, comparable published data on existing assays. While further clinical validation head-to-head comparisons are needed fully establish role S-PLEX assay, these demonstrate utility pathology.

Language: Английский

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Combining plasma Aβ and p-tau217 improves detection of brain amyloid in non-demented elderly

Alzheimer s Research & Therapy, Journal Year: 2024, Volume and Issue: 16(1)

Published: May 23, 2024

Abstract Background Maximizing the efficiency to screen amyloid-positive individuals in asymptomatic and non-demented aged population using blood-based biomarkers is essential for future success of clinical trials early stage Alzheimer’s disease (AD). In this study, we elucidate utility combination plasma amyloid-β (Aβ)-related tau phosphorylated at threonine 217 (p-tau217) predict abnormal Aβ-positron emission tomography (PET) preclinical prodromal AD. Methods We designed cross-sectional study including two ethnically distinct cohorts, Japanese trial-ready cohort preclinica AD (J-TRC) Swedish BioFINDER study. J-TRC included 474 (CDR 0: 331, CDR 0.5: 143). Participants underwent Aβ p-tau217 assessments, Aβ-PET imaging. Findings were replicated 177 participants (cognitively unimpaired: 114, mild cognitive impairment: 63). both Aβ(1-42) (Aβ42) Aβ(1-40) (Aβ40) measured immunoprecipitation-MALDI TOF mass spectrometry (Shimadzu), was with an immunoassay on Meso Scale Discovery platform (Eli Lilly). Results 81 from 71 BioFINDER. Plasma Aβ42/Aβ40 ratio individually showed moderate high accuracies when detecting scans, which improved by combining age, sex APOE genotype models. J-TRC, highest AUCs observed models p-tau217/Aβ42 ratio, , whole (AUC = 0.936), p-tau217, 0 group 0.948), 0.5 0.955), respectively. Each subgroup results BioFINDER, where seen Aβ42/40 cognitively unimpaired 0.938), impairment 0.914). Conclusions Combination Aβ-related exhibits performance predicting positivity. Adding basic information (i.e., sex, ε genotype) prediction AD, but not could be highly useful pre-screening

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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Clinical trials in dementia with Lewy bodies: the evolving concept of co-pathologies, patient selection and biomarkers

Current Opinion in Neurology, Journal Year: 2023, Volume and Issue: unknown

Published: June 28, 2023

Purpose of review Currently, no disease modifying therapies (DMTs) have been approved for use in dementia with Lewy bodies (DLB). Clinical trials face difficulties due to the clinical and neuropathological heterogeneity condition a diverse array neuropathogenic mechanisms contributing phenotype. The purpose this is describe how recent advances development biofluid biomarkers may be used tackle some these challenges. Recent findings Biomarkers are essential both support accurate diagnosis DLB delineate influence coexisting pathologies. α-synuclein seeding amplification assays (SAA) allow identification from prodromal stages DLB. Additionally, validation plasma phosphorylated tau ongoing offers an accessible biomarker indicate existence AD co-pathology. Use group stratification growing likely increasing importance future. Summary In vivo can enhance patient selection allowing greater diagnostic accuracy, more homogeneous trial population, by co-pathology create subgroups most derive therapeutic benefit DMTs.

Language: Английский

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