| The associations of serum isoleucine with Alzheimer`s disease on assisting diagnosis, predicting conversion and assessing cognition |
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Xiao-jun Jing1, Zhi-yuan Zan1, Xin Zhou1, Yong-lan Xiong2, Shu-jiang Ren1, Hua Zhang1, the Alzheimer’s Disease Neuroimaging Initiative |
1Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
2Department of Neurology, the Banan Hospital of Chongqing Medical University, Chongqing 401320, China |
Correspondence:
Hua Zhang, Tel: +86-23-89012009, Fax: +86-23-68708697,
Email: zhanghuapro@hospital.cqmu.edu.cn
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Received: 27 December 2023 • Revised: 10 March 2024 • Accepted: 16 April 2024 |
| Abstract |
Background
Advances in blood biomarker discovery have enabled the improved diagnosis and prognosis of Alzheimer's disease (AD). Most branched-chain amino acids, except isoleucine (Ile), are correlated with both mild cognitive impairment (MCI) and AD. Therefore, this study investigated the association between serum Ile levels and MCI/AD.
Methods
This study stratified 700 participants from the Alzheimer's Disease Neuroimaging Initiative database into four diagnostic groups: cognitively normal, stable MCI, progressive MCI, and AD. Analysis of covariance and chi-square analyses were used to test the demographic data. Receiver operating curve analyses were used to calculate the diagnostic accuracy of different biomarkers and were compared using MedCalc 20. Additionally, Cox proportional hazards models were used to measure the ability of serum Ile levels to predict disease conversion. Finally, a linear mixed-effects model was used to evaluate the associations between serum Ile levels and cognition, brain structure, and metabolism.
Results
Serum Ile concentration was decreased in AD and demonstrated significant diagnostic efficacy. The combination of serum Ile and cerebrospinal fluid (CSF) phosphorylated tau (P-tau) levels improved the diagnostic accuracy in AD compared to T-tau alone. Serum Ile levels significantly predicted the conversion from MCI to AD (cutoff value = 78.3 μM). Finally, the results of this study also revealed a correlation between serum Ile levels and the Alzheimer's Disease Assessment Scale cognitive subscale Q4.
Conclusions
Serum Ile level may be a potential biomarker of AD. Ile had independent diagnostic efficacy and significantly improved the diagnostic accuracy of CSF P-tau in AD. Patients with MCI with a lower serum Ile level had a higher risk of progression to AD and a worse cognition assessment. |
| Key Words:
Alzheimer’s disease, isoleucine, mild cognitive impairment |
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