Baseline serum glutamate: Implications for diagnosis and prediction in mild cognitive impairment and Alzheimer's disease of the Alzheimer's Disease Neuroimaging Initiative

Purpose: Numerous studies have highlighted a close link between metabolic imbalances and Alzheimer's Disease (AD). The advancement of metabolomics has recently enabled the exploration of characteristic metabolic changes associated with AD. Studies indicate that serum glutamate (Glu) levels may correlate with mild cognitive impairment (MCI) and AD. This study aims to further elucidate the characteristics of baseline serum Glu levels in MCI and AD. Methods: This study included 783 participants from the Alzheimer's Disease Neuroimaging Initiative-1 (ADNI-1) cohort, categorized into cognitively normal (CN, n = 224), stable MCI (sMCI, n = 181), progressive MCI (pMCI, n = 193), and AD (n = 185). The study aimed to analyze the diagnostic value of baseline serum Glu, to explore its predictive capability for the progression from CN to MCI or AD, and from MCI to AD, and to analyze the relationship between serum Glu and cerebrospinal fluid (CSF) biomarkers and cognitive functions in different diagnostic groups. Results: Compared to the CN and sMCI groups, the pMCI group showed significantly lower levels of serum Glu, and the AD group also had lower Glu levels compared to the sMCI group. However, serum Glu did not show significant diagnostic value for MCI and AD. Lower levels of serum Glu could predict the progression from MCI to AD. Conclusion: Serum Glu levels can predict the progression from MCI to AD, suggesting that it could provide new insights into the pathophysiological mechanisms of AD. However, serum Glu may not be an ideal peripheral biomarker for AD.