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. 2020 May 11;12(1):55.
doi: 10.1186/s13195-020-00621-6.

Longitudinal trajectories of Alzheimer's ATN biomarkers in elderly persons without dementia

Meng-Shan Tan  1 , Xi Ji  2 , Jie-Qiong Li  1 , Wei Xu  1 , Hui-Fu Wang  1 , Chen-Chen Tan  1 , Qiang Dong  3 , Chuan-Tao Zuo  4 , Lan Tan  1   2 , John Suckling  5   6   7 , Jin-Tai Yu  8 ; Alzheimer’s Disease Neuroimaging Initiative
Affiliations

Longitudinal trajectories of Alzheimer's ATN biomarkers in elderly persons without dementia

Meng-Shan Tan et al. Alzheimers Res Ther. .

Abstract

Background: Models of Alzheimer's disease (AD) pathophysiology posit that amyloidosis [A] precedes and accelerates tau pathology [T] that leads to neurodegeneration [N]. Besides this A-T-N sequence, other biomarker sequences are possible. This current work investigates and compares the longitudinal trajectories of Alzheimer's ATN biomarker profiles in non-demented elderly adults from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort.

Methods: Based on the ATN classification system, 262 individuals were identified before dementia diagnosis and accompanied by baseline and follow-up data of ATN biomarkers (CSF Aβ42, p-tau, and FDG-PET). We recorded the conversion processes in ATN biomarkers during follow-up, then analyzed the possible longitudinal trajectories and estimated the conversion rate and temporal evolution of biomarker changes. To evaluate how biomarkers changed over time, we used linear mixed-effects models.

Results: During a 6-120-month follow-up period, there were four patterns of longitudinal changes in Alzheimer's ATN biomarker profiles, from all negative to positive through the course of the disease. The most common pattern is that A pathology biomarker first emerges. As well as the classical A-T-N sequence, other "A-first," "T-first," and "N-first" biomarker pathways were found. The N-A-T sequence had the fastest rate of pathological progression (mean 65.00 months), followed by A-T-N (mean 67.07 months), T-A-N (mean 68.85 months), and A-N-T sequences (mean 98.14 months).

Conclusions: Our current work presents a comprehensive analysis of longitudinal trajectories of Alzheimer's ATN biomarkers in non-demented elderly adults. Stratifying disease into subtypes depending on the temporal evolution of biomarkers will benefit the early recognition and treatment.

Keywords: ADNI; Alzheimer’s disease; Amyloid; Biomarker; Neurodegeneration; Tau.

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Conflict of interest statement

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Fig. 1
Fig. 1
Study demographics and ATN biomarker profiles at baseline and follow-up. The analyses included 262 non-demented elderly individuals, with baseline and follow-up data of CSF Aβ42, p-tau, and FDG-PET metabolism, with seven different ATN biomarker profiles based on ATN classification. During the follow-up period of 6 to 120 months, the detailed process of the changes in ATN biomarker profiles in these individuals from the ADNI cohort was shown
Fig. 2
Fig. 2
Detailed conversion rate and temporal evolution of ATN biomarker changes in different sequences through the course of the disease. The follow-up time ranged from 6 to 120 months. Red fonts represent the conversion rate at different stages. Blue fonts represent the baseline estimated time to each biomarker change. The overall conversion rates of different biomarker sequences were shown, on the basis of the current follow-up data, while 46.34% of individuals did not have any ATN biomarker changes
Fig. 3
Fig. 3
Modeling longitudinal trajectories of Alzheimer’s ATN biomarkers. The model results of the baseline estimated months to each biomarker change, reflecting the temporal evolution of pathology over the course of the disease, and the detailed time points for each biomarker change. The N-A-T sequence had the fastest rate of pathological progression (mean 65.00 months), followed by the A-T-N (mean 67.07 months), then the T-A-N sequence (mean 68.85 months), and finally the A-N-T sequence (mean 98.14 months)
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