Amino Acid Levels as Potential Biomarker of Elderly Patients with Dementia

Abstract

Dementia is a clinical syndrome characterized by cognitive impairment, in which there is disturbance of multiple higher cortical functions. The primary risk factor of dementia is old age, and due to significant changes in the worldwide demographic structure, the prevalence of cognitive impairment is increasing dramatically with aging populations in most countries. Alzheimer’s disease is the predominant and leading cause of dementia. The aim of this study was to evaluate the modifications of amino acids that characterize the initial stages of dementia to help our understanding of the complex and multifactorial pathogenesis of neurodegenerative disorders. A total of 123 participants were divided into two groups: healthy elderly subjects and patients with mild or moderate dementia. The results of this study indicate that the serum levels of three amino acids were changed significantly in patients with dementia, in relation to the subjects without dementia. In particular, we observed differences in concentrations for serine, arginine and isoleucine (all of them were significantly increased in patients with dementia, compared with the control group). Our results suggest that the metabolisms of some amino acids seem be changed in patients with dementia. We conclude that amino acid profiling might be helpful for the better understanding of biochemical and metabolic changes related to the pathogenesis and progression of dementia. However, considering the multifactorial, heterogenous and complex nature of this disease, validation with a greater study sample in further research is required.

Investigating the causal association between branched-chain amino acids and Alzheimer's disease: A bidirectional Mendelian randomized study

“…In a prospective study of eight cohorts, BCAAs were found to be negatively associated with dementia and the risk of AD (31). However, in another observational study, serum isoleucine levels were elevated in dementia, compared with HC (33). Similarly, elevated blood levels of BCAAs in patients with AD were reported in a small sample study cohort (17).…”

Branched-chain amino acids and the risks of dementia, Alzheimer’s disease, and Parkinson’s disease

“…Nevertheless, there were elevated BCAA concentrations in the serum of AD patients in another sample study ( Li et al, 2018 ). Similarly, serum isoleucine levels were elevated in dementia patients, compared with healthy controls ( Socha et al, 2020 ). Combined with the results of this study, we speculate that these inconsistent results occurred in ordinary observational studies due to the limited sample size and dynamic changes in blood concentrations and degradation of BCAA ( Lynch and Adams, 2014 ; Siddik et al, 2022 ).…”

Circulating Neurofilament Light Chain Levels Increase with Age and Are Associated with Worse Physical Function and Body Composition in Men but Not in Women

“…Dysregulation in lipid metabolism may contribute to neuroinflammation, oxidative stress, decline in physical function with aging, and the formation of pathological protein aggregates [ 26 ]. Plasma metabolomic analysis has shown perturbations in amino acid levels, particularly alterations in aromatic amino acids (such as tryptophan and phenylalanine), branched-chain amino acids (BCAAs) (e.g., leucine, isoleucine, and valine), and lysophosphatidylcholines (LPC), with aging and in individuals with neurodegenerative disorders [ 27 , 28 , 29 , 30 , 31 , 32 ]. In association with metabolomic changes, it is also evidenced that neurodegeneration and aging can also induce changes in body composition which in turn might accelerate the onset of neurodegenerative processes and or diseases [ 33 , 34 ].…”