The Amyloid, Tau, and Neurodegeneration (A/T/N) Classification Applied to a Clinical Research Cohort with Long-Term Follow-Up

Grøntvedt, Gøril Rolfseng; Lauridsen, Camilla; Berge, Guro; White, Linda R.; Salvesen, Øyvind; Bråthen, Geir; Sando, Sigrid Botne

doi:10.3233/jad-191227

Cited by 39 publications

(44 citation statements)

References 35 publications

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“…As the ratio of Aβ42 to T-tau can be artificially increased via increases in T-tau levels only, however, (e.g., due acute brain disorders such as trauma or stroke) it has been recommended that CSF AD biomarkers are to be interpreted as independent measures [ 9 ]. When applying the Aβ (A), tau (T) and neurodegeneration (N) (A/T/N) classification system using CSF AD biomarkers to extended follow-up data (up to 10 years), while the highest proportion of progression from MCI to AD dementia was seen in patients who were A+T+N+, progression was also common in patients showing A-T+N+ and A-T-N- [ 109 ].…”

Section: Resultsmentioning

confidence: 99%

2020 update on the clinical validity of cerebrospinal fluid amyloid, tau, and phospho-tau as biomarkers for Alzheimer’s disease in the context of a structured 5-phase development framework

Leuzy

Ashton

Mattsson‐Carlgren

et al. 2021

Eur J Nucl Med Mol Imaging

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Purpose In the last decade, the research community has focused on defining reliable biomarkers for the early detection of Alzheimer’s disease (AD) pathology. In 2017, the Geneva AD Biomarker Roadmap Initiative adapted a framework for the systematic validation of oncological biomarkers to cerebrospinal fluid (CSF) AD biomarkers—encompassing the 42 amino-acid isoform of amyloid-β (Aβ42), phosphorylated-tau (P-tau), and Total-tau (T-tau)—with the aim to accelerate their development and clinical implementation. The aim of this work is to update the current validation status of CSF AD biomarkers based on the Biomarker Roadmap methodology. Methods A panel of experts in AD biomarkers convened in November 2019 at a 2-day workshop in Geneva. The level of maturity (fully achieved, partly achieved, preliminary evidence, not achieved, unsuccessful) of CSF AD biomarkers was assessed based on the Biomarker Roadmap methodology before the meeting and presented and discussed during the workshop. Results By comparison to the previous 2017 Geneva Roadmap meeting, the primary advances in CSF AD biomarkers have been in the area of a unified protocol for CSF sampling, handling and storage, the introduction of certified reference methods and materials for Aβ42, and the introduction of fully automated assays. Additional advances have occurred in the form of defining thresholds for biomarker positivity and assessing the impact of covariates on their discriminatory ability. Conclusions Though much has been achieved for phases one through three, much work remains in phases four (real world performance) and five (assessment of impact/cost). To a large degree, this will depend on the availability of disease-modifying treatments for AD, given these will make accurate and generally available diagnostic tools key to initiate therapy.

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Section: Resultsmentioning

confidence: 99%

2020 update on the clinical validity of cerebrospinal fluid amyloid, tau, and phospho-tau as biomarkers for Alzheimer’s disease in the context of a structured 5-phase development framework

Leuzy

Ashton

Mattsson‐Carlgren

et al. 2021

Eur J Nucl Med Mol Imaging

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“…Inspections revealed that only two patients had the A‐T‐N+ profile, one of whom received the diagnosis of hippocampal sclerosis probably due to TDP43 proteinopathy and the other was inconclusive. However, other authors 83 recently reported that some individuals with amnestic MCI progressed to clinical AD dementia within all four major A/T/N groups including A‐T + N+ and A‐T‐N‐. They suggested that when selecting individuals for research, a combination of the A/T/N framework and clinical status may be necessary because the prognostic value of the former depends on the latter.…”

Section: Knowledge Creationmentioning

confidence: 99%

“…An interesting single case was recently published that sheds new light on the causal mechanisms of AD dementia and the A/T/N framework. 84…”

Section: Cost Of Biomarkers (Prioritymentioning

confidence: 99%

Dementia in Latin America: Paving the way toward a regional action plan

Parra¹,

Báez²,

Sedeño³

et al. 2020

Alzheimer's & Dementia

121

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Across Latin American and Caribbean countries (LACs), the fight against dementia faces pressing challenges, such as heterogeneity, diversity, political instability, and socioeconomic disparities. These can be addressed more effectively in a collaborative setting that fosters open exchange of knowledge. In this work, the Latin American and Caribbean Consortium on Dementia (LAC‐CD) proposes an agenda for integration to deliver a Knowledge to Action Framework (KtAF). First, we summarize evidence‐based strategies (epidemiology, genetics, biomarkers, clinical trials, nonpharmacological interventions, networking, and translational research) and align them to current global strategies to translate regional knowledge into transformative actions. Then we characterize key sources of complexity (genetic isolates, admixture in populations, environmental factors, and barriers to effective interventions), map them to the above challenges, and provide the basic mosaics of knowledge toward a KtAF. Finally, we describe strategies supporting the knowledge creation stage that underpins the translational impact of KtAF.

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“…SNAP does not represent preclinical AD, but includes one or more neuropathological processes or diseases other than AD [37]. SNAP is common in both clinically asymptomatic and cognitively impaired individuals [38,39]. In our study, the presence of SNAP was relatively consistent across different clinical groups (HC24.5%, MCI 22.3%, and AD 21.1%).…”

Section: Discussionmentioning

confidence: 48%

Optimal ATN biomarkers and their role in predicting cognitive progress of mild cognitive impairment

Song

Liu

et al. 2021

Preprint

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Background It is of great significance to investigate the optimal cerebrospinal fluid (CSF) and magnetic resonance image biomarkers of ATN system and clarify their predictive value in cognitive progression of mild cognitive impairment individuals (MCI). Methods 147 healthy control (HC), 197 patients with MCI, and 128 patients with Alzheimer’ Disease (AD) were included from the ADNI database. All MCI patients were followed up from 6 to 60 months. The amyloid (A) was assessed by CSF Aβ42 or Aβ42/Aβ40. The tau pathology (T) was assessed by CSF p-tau. The neurodegeneration (N) was assessed by radiomics of the whole brain MRI or by CSF t-tau. Biomarkers with larger area under the receiver operating characteristic curve (AUC) in the discrimination of AD and HC were considered to be the optimal biomarkers. The conversion rates of different ATN profiles in MCI subjects during follow-up were analyzed using Kaplan-Meier estimates and compared using the Log-rank test. Results The CSF Aβ 42 and the radiomics signature (AUC 0.822 and 0.998, respectively) were identified as the optimal A and N biomarkers, respectively. For MCI patients of the Alzheimer continuum, there was no significant difference in the progression rate of A + T − N− and A − T−N − profiles (p > 0.05). The A + T + N−, A + T − N + profiles had a significant higher progression rate than that of the A + T − N− patients (all p < 0.05). For MCI of the suspected non-AD pathophysiology (SNAP), patients with the A − T−N + profile (p < 0.05) showed significant higher progression rate than A − T−N − profile. There was no significant difference in the progression rate of A − T + N − and A − T−N − profiles (p > 0.05). Discussion We proposed a new radiomics method to assess N accurately and ascertained the optimal A/T/N biomarkers for the discrimination of HC and AD. For MCI patients of the Alzheimer continuum, isolated A + was indicator of cognitive stability, while the abnormality of T and N, respectively or simultaneously, indicated the high risk of progression. For MCI patients of SNAP, isolated T + indicated the cognitive stability, while the appearance of N + indicated the high risk of progression.

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The Amyloid, Tau, and Neurodegeneration (A/T/N) Classification Applied to a Clinical Research Cohort with Long-Term Follow-Up

Cited by 39 publications

References 35 publications

2020 update on the clinical validity of cerebrospinal fluid amyloid, tau, and phospho-tau as biomarkers for Alzheimer’s disease in the context of a structured 5-phase development framework

2020 update on the clinical validity of cerebrospinal fluid amyloid, tau, and phospho-tau as biomarkers for Alzheimer’s disease in the context of a structured 5-phase development framework

Dementia in Latin America: Paving the way toward a regional action plan

Optimal ATN biomarkers and their role in predicting cognitive progress of mild cognitive impairment

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