Serum Homocysteine as a Potential Dynamic Biomarker for Staging and Monitoring Progression in Alzheimer’s Disease

Cong Wu,1 Chunli Wu,2 Xiaoyu Yin,2 Changyang Zhong2 1The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 2Cerebrovascular Disease Department, Hangzhou Third People’s Hospital, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Changyang Zhong, Department of Cerebrovascular Disease, Hangzhou Third People’s Hospital, Hangzhou, Zhejiang, 310009, People’s Republic of China, Email [email protected]: Reliable biomarkers are urgently needed for the early diagnosis and dynamic monitoring of Alzheimer’s disease (AD). Serum homocysteine (Hcy) has been increasingly investigated but with inconsistent association to AD severity.Objective: To investigate the correlation between serum Hcy levels and AD severity/cognitive function, and to evaluate its clinical utility as a dynamic monitoring indicator for the disease.Methods: This retrospective study enrolled 80 AD patients (stratified by Mini-Mental State Examination [MMSE] score: 40 mild, 28 moderate, 12 severe) and 80 healthy controls from the Cerebrovascular Disease outpatient and inpatient departments of our hospital between January 2022 and December 2024. Fasting serum Hcy was measured via chemiluminescent immunoassay. Correlation with cognitive scores and severity discrimination were analyzed.Results: Serum Hcy levels were significantly higher in the AD group than controls (21.2 ± 6.6 vs 14.5 ± 4.8 μmol/L, p < 0.05), increasing with severity (mild: 16.8 ± 3.2, moderate: 21.2 ± 4.5, severe: 25.6 ± 5.8 μmol/L, p < 0.001). A strong inverse correlation with MoCA scores was observed (r = − 0.76, p < 0.01). ROC analysis showed an AUC of 0.87 for discriminating AD severity, with an optimal cut-off of 17.5 μmol/L (sensitivity 78%, specificity 72%). After 6 months of B-vitamin intervention, Hcy decreased significantly with cognitive improvement.Conclusion: Serum Hcy correlates strongly with AD severity and cognitive decline, supporting its potential as a dynamic biomarker for monitoring progression and treatment response.Keywords: Alzheimer’s disease, homocysteine, cognitive decline, biomarker, dynamic monitoring