A biological classification for Alzheimer’s disease - Amyloid, Tau and Neurodegeneration (A/T/N): results from the Argentine-Alzheimer’s Disease Neuroimaging Initiative

Abstract

Given the current controversies between the clinical and neuropathological data in Alzheimer's disease (AD), Jack et al. (2016) proposed a new biomarker based classification named as the ATN system with the goal of developing a more accurate characterization and understanding of the sequence of events that lead to cognitive impairment. Opposed to the previous concepts (Albert et al., 2011; Sperling et al., 2011), here the classification is entirely based on biomarkers (Jack et al., 2018). The seven major AD biomarkers are divided in three binary classes: "A" refers to Aβ biomarkers (amyloid PET or CSF Aβ42), "T" to tau pathology biomarker (CSF p-tau or tau PET), and "N" a quantitative or topographic biomarker of neurodegeneration (CSF t-tau, FDG-PET or structural MRI) and each biomarker is rated as positive or negative (Jack et al., 2016; 2018). The aim of this study was to describe the A/T/N research framework classification for AD in the Argentine ADNI cohort and to explore the prediction to develop dementia in a prospective two-year follow-up. A cohort of 56 individuals (23 Mild Cognitive Impairment [MCI], 12 AD and 14 controls) were studied with the ADNI-2 protocol, which has been described in detail elsewhere (Russo et al., 2014). Patients were categorized according to A/T/N and were followed longitudinally (baseline, at 12-and 24-month follow-up visits). A + /T + /N + at baseline was found in 2/14 controls (14%), 2/10 early MCI (20%), 6/13 late MCI (46%) and 11/12 mild dementia (91%); Suspected non-AD pathophysiology (SNAP, A-/T-/N +) was found in 1/14 controls (7%), 2/10 early MCI (20%), 2/13 late MCI (15%) and 1/12 mild dementia (8%); and A-/T-/N-: 8/14 (57%) of normal controls, 4/10 (40%) of e-MCI, 3/13 (23%) of l-MCI and 0/12 (0%) of mild dementia. The first two-year survival analysis was based on clinical classification among normal controls 1/14 (7%), early MCI 2/10 (20%) and late MCI 6/13 (46%). The second two-year survival analysis

Prognostic value of ATN Alzheimer biomarkers: 60‐month follow‐up results from the Argentine Alzheimer's Disease Neuroimaging Initiative

“…When we studied rate of progression to dementia based on clinical classification, 10% of normal controls, 20% of e‐MCI, and 46% of l‐MCI patients progressed after 2 years follow‐up 24 . In the late MCI group, percentage of annual progression in our series was higher than the classical 5% to 10% per year described by Petersen et al.…”

“…The goal of our study was to apply the ATN classification at baseline in an Argentine ADNI cohort and study risk of progression to dementia based on biomarker results. The Memory and Aging Center from the Instituto de Investigaciones Neurologicas FLENI, in Buenos Aires, Argentina, was the first center in Latin America to routinely use AD biomarkers 22‐24 . No significant differences were found between MCI patient groups in cognitive functions, except for episodic memory (l‐MCI patients scored lower on delayed recall of the RAVLT), behavioral symptoms (evaluated using NPI‐Q and GDS), and functional activities (FAQ).…”

The Worldwide Alzheimer's Disease Neuroimaging Initiative: ADNI‐3 updates and global perspectives

“…After 5 years of follow‐up, the overall conversion rate to dementia was 21%. Cognitive testing data significantly correlated with CSF amyloid levels in participants 35 ; however, total CSF tau and p‐tau were the strongest conversion predictors 34,36 . The researchers have described the capacity of several biomarkers to predict cognitive impairment 37,38 .…”

“…Cognitive testing data significantly correlated with CSF amyloid levels in participants 35 ; however, total CSF tau and p-tau were the strongest conversion predictors. 34,36 The researchers have described the capacity of several biomarkers to predict cognitive impairment. 37,38 Notably, Argentina ADNI is the first group in Latin America to perform tau PET scans (23 performed to date).…”

Rediscovering an old friend: a role for insulin growth factor-2 in reducing neurodegeneration, decreasing amyloid beta, and improving memory

“…As Xia et al (2019) remind us, the two pathological hallmarks of AD are amyloid plaques, which are enriched with extracellular amyloid beta (Aβ), and intracellular neurofibrillary tangles, which are composed of hyperphosphorylated tau proteins. These pathological features of AD impair neuronal and synaptic function, resulting in an associated decline in cognitive abilities (Allegri et al, 2019;Mirandez et al, 2017). Despite our increased understanding of both of these pathological components of AD over the past decades, the field has still not identified pathways and associated molecules that can prevent neurodegeneration.…”