Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 10 05 1 19 Zichao Wang Shenyang Pharmaceutical University, Shenyang, Liaoning, China Hongkun Zhao Shenyang Pharmaceutical University, Shenyang, Liaoning, China 2026 05 09 2026 06 09 This study characterized lysosome-associated membrane protein 1 (LAMP1)-related immunometabolic abnormalities in Alzheimer disease (AD) and mild cognitive impairment (MCI) using peripheral blood transcriptomic data from three GEO cohorts (GSE63060, GSE63061, and GSE140829). After preprocessing and cross-cohort integration, directionally consistent LAMP1-related genes were identified, and a composite index comprising ITGAM, ITGB2, LAMP1, and GBA was constructed. Analyses included correlation, group comparison, ROC analysis, random-effects meta-analysis, and leave-one-out validation.A total of 1262 samples were included. LAMP1 was consistently elevated in AD and MCI versus controls, with pooled effect sizes of Hedges’ g=0.330 and 0.514, respectively. Immune-, lysosome-, and metabolism-related genes, including ITGAM, ITGB2, GBA, GNS, RXRA, G6PD, and TCIRG1, showed concordant changes across both conditions. The 4-gene index was also increased in AD and MCI (g= 0.543 and 0.648), and LAMP1 strongly correlated with the 3-gene index excluding itself (r=0.760). These findings suggest reproducible peripheral blood transcriptomic alterations related to immune activation, lysosomal dysfunction, and metabolic regulation in AD and MCI. As this was a secondary analysis of public datasets without adjustment for blood-cell composition, the results should be interpreted as exploratory molecular signals rather than definitive diagnostic biomarkers. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4831 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4831/2433